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• Published: 06 November 2021

Structure and stability of symptoms in first episode psychosis: a longitudinal network approach

• Siân Lowri Griffiths   ORCID: orcid.org/0000-0003-0031-7174 1 ,
• Samuel P. Leighton   ORCID: orcid.org/0000-0002-3999-4204 2 ,
• Pavan Kumar Mallikarjun 1 ,
• Georgina Blake 3 ,
• Linda Everard 4 ,
• Peter B. Jones   ORCID: orcid.org/0000-0002-0387-880X 5 ,
• David Fowler 6 ,
• Joanne Hodgekins 7 ,
• Tim Amos 8 ,
• Nick Freemantle 9 ,
• Vimal Sharma 10 ,
• Max Marshall 11 ,
• Paul McCrone 12 ,
• Swaran P. Singh 13 ,
• Max Birchwood 13   na1 &
• Rachel Upthegrove   ORCID: orcid.org/0000-0001-8204-5103 1 , 3   na1  

Translational Psychiatry volume  11 , Article number:  567 ( 2021 ) Cite this article

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• Schizophrenia

Early psychosis is characterised by heterogeneity in illness trajectories, where outcomes remain poor for many. Understanding psychosis symptoms and their relation to illness outcomes, from a novel network perspective, may help to delineate psychopathology within early psychosis and identify pivotal targets for intervention. Using network modelling in first episode psychosis (FEP), this study aimed to identify: (a) key central and bridge symptoms most influential in symptom networks, and (b) examine the structure and stability of the networks at baseline and 12-month follow-up. Data on 1027 participants with FEP were taken from the National EDEN longitudinal study and used to create regularised partial correlation networks using the ‘EBICglasso’ algorithm for positive, negative, and depressive symptoms at baseline and at 12-months. Centrality and bridge estimations were computed using a permutation-based network comparison test. Depression featured as a central symptom in both the baseline and 12-month networks. Conceptual disorganisation, stereotyped thinking, along with hallucinations and suspiciousness featured as key bridge symptoms across the networks. The network comparison test revealed that the strength and bridge centralities did not differ significantly between the two networks (C = 0.096153; p  = 0.22297). However, the network structure and connectedness differed significantly from baseline to follow-up (M = 0.16405, p  = <0.0001; S = 0.74536, p  = 0.02), with several associations between psychosis and depressive items differing significantly by 12 months. Depressive symptoms, in addition to symptoms of thought disturbance (e.g. conceptual disorganisation and stereotyped thinking), may be examples of important, under-recognized treatment targets in early psychosis, which may have the potential to lead to global symptom improvements and better recovery.

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Introduction.

Psychosis is a disorder of complex psychopathology, with heterogeneous illness trajectories, particularly in the early stages [ 1 ]. Although early recognition and treatment bring substantial benefit [ 2 ], outcomes remain poor for many with first episode psychosis (FEP) [ 3 ]. Understanding how symptoms are structured, and which key symptoms play a pivotal role in maintaining psychopathology, may help to identify new treatment targets and improve outcomes.

Symptom interactions in early stages of illness are likely to be fluid and may change in strength and quality over time [ 4 ]. The interconnectedness of positive, negative and co-morbid affective symptoms in psychosis has previously been explored based on latent structures of symptomatology [ 5 , 6 ], whereby symptoms may be connected via a single underlying latent variable (psychosis), and non-psychosis symptoms considered of secondary importance [ 6 ]. However, it is also suggested that the flame of positive symptoms is driven by affective dysfunction in the early years, and primary negative symptoms become prominent only after acute psychosis wanes [ 7 , 8 ]. With the availability of novel modelling statistics and large longitudinal data, it is now possible to explore such assumptions. Network modelling of psychopathology does not presume a latent variable: individual symptoms are connected by statistical relationships, and large datasets can be modelled to reveal new structures [ 9 , 10 , 11 ]. Network analyses completed over different time-points can explore the connectivity, stability, and structure of symptoms over time, which may provide key information for interventions targeted at individuals likely on a pathway to treatment resistance [ 12 ].

Network analysis studies in chronic schizophrenia have identified central symptoms such as paranoid ideation, apathy, avolition, and depression, which are reported to activate other symptoms via a contagion effect, leading to the maintenance of psychopathology [ 13 , 14 , 15 , 16 , 17 , 18 ]. Others have explored changes in network structure in those with and without remitted status [ 15 , 17 , 19 ], or in response to antipsychotic treatment [ 4 , 14 , 20 , 21 ]. Whilst these findings are informative, they are limited to older individuals with enduring illness, and have been conducted with relatively small sample sizes.

Identifying early treatment targets in the ‘critical’ phase of illness has the potential for greatest impact [ 22 ]. A small number of studies have applied network modelling to understand psychosis symptoms in young people. Preliminary findings suggest that the strength of network architectures and symptom connectedness may indicate psychosis liability. However, these findings remain exploratory given the small ( N  = 16) cross-sectional nature of Schmidt et al’s study [ 23 ], and the second study by Wigman et al was based on a community (rather than a clinical) sample with psychotic-like-experiences [ 24 ]. Finally, two recent papers in FEP have demonstrated the potential role of depression and general psychopathology with psychotic symptom expression. In the first, Betz and colleagues (2020) showed that general psychopathology mediated the relationship between the burden of life events and expression of psychotic symptoms, supporting an affective pathway to psychosis [ 6 , 25 , 26 ]. Second, Herniman and colleagues (2021) demonstrated that depression symptoms were highly interrelated with positive and negative symptoms, suggesting that depression symptoms might be better conceptualized as intrinsic to psychosis [ 27 ]. Though these studies are informative, they are limited by their cross-sectional design and small samples of young people with FEP.

In this present study, we used a large, diverse, national FEP cohort to explore the structure and inter-relationships between symptoms in early psychosis, using a robust network analyses design to: (a) identify network structures at baseline and 12-months follow-up; and b) identify key central and bridge symptoms that may offer treatment targets for novel interventions.

The EDEN dataset is a longitudinal naturalistic study of 1027 individuals with FEP, recruited from 14 early intervention services (EIS) across England (2005 to 2010; ethical approval REC: 05/Q0102/44.); the methodology and baseline characteristics have been outlined previously [ 28 ], but an overview of sample characteristics can be found in Table 1 . In summary, observer rated assessments were conducted at baseline (upon entry to EIS), and at a 6 and 12-month timepoint. Complete data on the variables of interest were available for 718 participants by 12-month follow-up.

The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving human patients were approved by Suffolk Local Research Ethics Committee, UK. Approval number: 05/Q0102/44. Written informed consent was obtained from all patients.

Assessments

The Positive and Negative Syndrome Scale (PANSS) [ 29 ]. PANSS consists of 30-items measuring severity of positive, negative and general symptoms. Each item is scored between 1 (= absent) to 7 (= extreme). For this study, the Positive Scale (seven items) and Negative Scale (seven items) were used.

The Calgary Depression Scale for Schizophrenia (CDSS) [ 30 ]. The CDSS includes a total of 9 depressive symptoms (eight structured questions and one interviewer observation) and a scale that ranges from 0 (absent) to 3 (severe).

Statistical analysis

Descriptive data analysis and network modelling were carried out using R, Version 4.0.3 [ 31 ]. (Code for the network analysis is available in the supplementary materials).

Missing data

For the full EDEN sample ( N  = 1027), there were 895 complete cases at baseline, 757 complete cases at 12 months, and 618 complete cases across the two time points. Item level data were missing for 6.2% of the sample at baseline, and 23·9% at 12-months. Missing data were imputed using an iterative Markov Chain Monte Carlo method, which can concurrently generate Bayesian simulations for binary distributions for cases with incomplete data for all cases [ 32 ]. While missing network data can be problematic, there is a lack of simulation studies testing the performance of imputation techniques alongside variable selection methods. We chose EBICglasso over pairwise / likelihood techniques, based on prior research within the structural equation literature showing superior performance of lasso-based methods when the number of variables with missing is large, and when there’s a range of parameters which are also likely to be moderately or highly correlated [ 33 ]. Nevertheless, sensitivity analyses were conducted using the complete cases to compare any network differences when using the imputed data (please see results section). Finally, we decided not to include the 6-month network due to the increased complexity it would add to the analysis, reducing the interpretability.

Network estimation

Two networks were estimated using the full EDEN sample ( N  = 1027), which included complete and imputed cases at baseline and 12-months. We used the ‘bootnet’ package [ 11 ] which implements the ‘EBICglasso’ algorithm from the ‘qgraph’ package [ 34 ], in turn uses the ‘glasso’ algorithm from the ‘glasso’ package [ 35 ]. Network structures were estimated using regularised partial correlation, with coefficients ranging from -1 to 1, representing the association between two nodes after controlling for all other possible information. Partial correlations can be visualised in a weighted network structure with each node representing a variable (e.g. symptom), and each edge showing that two variables are not independent after conditioning all other variables. The edge weights are their partial correlation coefficients. Given the ordinal nature of the data, Spearman’s correlations were used to create covariance matrix via the ‘lavaan’ package [ 36 ]. The resulting covariance matrix is inputted into the ‘EBICglasso’ algorithm which uses the least absolute shrinkage and selection operator (lasso) regularisation [ 37 ], resulting in sparse networks. ‘EBICglasso’ selects the lasso tuning hyperparameter (λ) which minimises the Extended Bayesian Information Criterion (EBIC) [ 38 ]; the EBIC hyperparameter (γ) was set to zero in this study.

There remains contention as to whether regularization estimators, such as glasso, add benefit over more traditional frequentist approaches when estimating psychological networks. Indeed, it has recently been shown that classic methods, such as maximum likelihood estimator (MLE), outperform regularization when applied to low dimensional settings, common in psychology [ 39 , 40 ]. There is an inflated false positive rate inherent in regularization estimators, such as lasso, when the ratio of parameters to observations is low. We chose a regularization algorithm in this study because of its superiority in performance over non-regularized models when there is a wide range of predictor variables, which are likely to be highly correlated [ 33 , 40 ]. In such instances, lasso models have much lower Type II error rates, and are less likely to omit truly positive associations, suiting the more exploratory nature of this study [ 40 ].

The network structures are plotted using the ‘qgraph’ function (from ‘qgraph’ package) [ 34 ]; blue edges indicate positive partial correlations, and red edges indicatingnegative partial correlations. Nodes are placed using a modified version of the Fruchterman-Reingold algorithm [ 41 ], constraining the layout to be equal across the networks using the ‘averageLayout’ from the ‘qgraph’ package, enabling comparison. Maximum edge value was set to 0.5367 (the strongest edge identified across both networks); meaning saturation and edge thickness can be compared across graphs.

Network comparison test

A permutation-based test implemented within the ‘NetworkComparisonTest’ package [ 42 ] compared the baseline and 12 month symptom networks on global structure, overall connectivity level by average strength of all edge weights, and the difference in strength of individual edge weights. Finally, centrality estimates were computed using the “test centrality” command, which statistically assesses the centrality of symptoms across the two networks.

Centrality and bridge centrality estimation

The strength of nodes within each network were established by summing the absolute edge weights connected to a particular node [ 43 , 44 , 45 ]. The importance of each node in acting as a bridge to the three communities of symptoms (other than the community it originates), was calculated using the recently defined concept of bridge centrality implemented in the ‘networktools’ package [ 46 ]. We used the bridge strength estimate which indicates a node’s total connectivity with other communities. The top 20% scoring nodes (a cut-off giving an acceptable balance between sensitivity and specificity) on bridge strength was also indicated graphically [ 47 ].

Network accuracy and stability assessment

Bootstrapping methods were performed using the ‘bootnet’ package [ 48 ] to assess the accuracy and stability of the derived network parameters. We bootstrapped 95% CIs around the edge weights, the significance (α = 0·05) between the edges, and the significance (α = 0.05) between the centrality metric of the nodes for each network. The stability of the centrality indices was assessed via a case-dropping bootstrap, which were summarised using CS-coefficients (correlation stability), quantifying the proportion of the data that can be dropped to retain a correlation of at least 0.7 with 95% certainty. The CS-coefficient should be ideally above 0.5 but at least above 0.25 [ 49 ].

Full demographic characteristics of the EDEN sample have been outlined previously [ 28 ]. In summary, the sample ( n  = 1027) had a mean age of 21.3 years, 69% were male, and 70% were White British. The baseline network had greater positive, negative, and depressive symptoms compared to the 12-month network (Table 2 ).

Baseline network

At baseline, 52.2% of all possible edges were retained in the regularized networks. The network structure can be visualised in Fig. 1a . Distinct symptom communities can be visualised based on the three original symptom groups: PANSS Positive, PANSS Negative and CDSS.

A network structure for baseline is depicted in 1(a), and 1(b) for the 12 month network. Nodes (circles) represent individual symptoms. Orange nodes represent depressive items from the Calgary Depression Scale for Schizophrenia (CDSS). Blue nodes represent 7 negative symptoms from the PANSS scale, and green nodes represent items from the PANSS positive scale. Edge weights (lines) represent the strength of association between symptoms. Blue edges represent positive associations and red edges represent negative associations; denser lines represent stronger connections. P1_ = Delusions; P2 = Conceptual Organization; P3 = Hallucinatory Behaviour; P4 = Excitement; P5 = Grandiosity; P6 = Suspiciousness/Persecution; P7 = Hostility; N1 = Blunted Affect; N2 = Emotional Withdrawal; N3 = Poor Rapport; N4 = Passive/Apathetic Social Withdrawal; N5 = Difficulty in Abstract Thinking; N6 = Lack of Spontaneity and Flow of Conversation; N7 = Stereotyped Thinking; C1 = Depression; C2 = Hopelessness; C3 = Self Depreciation; C4 = Guilt Ideas of Reference; C5 = Pathological Guilt; C6 = Morning Depression; C7 = Early Awakening; C8 = Suicide; C9 = Observed Depression.

Depression (C1), Delusions (P1), and Lack of Spontaneity (N6) had the highest node strength centrality in the baseline network (Fig. 2 ). The top 20% scoring nodes on bridge strength (Fig. 3 ) were: blunted affect (N1), stereotyped thinking (N7), conceptual disorganization (P2), hallucinatory behaviour (P3), and suspiciousness (P6). Negative symptoms formed bridges with positive symptoms: stereotyped thinking bridged with conceptual disorganisation, and blunted affect was negatively associated with hostility. Depressive symptoms formed bridges with positive symptoms: Hallucinations and suicide, and suspiciousness and hopelessness were positively associated (Fig. 3a ).

Standardized z-scores are plotted for ease of interpretation. Higher scores represent higher centrality estimates (i.e. the symptom has greater influence in the network).

Network structures for baseline (3 a ), and 12-months (3 b ), display the top 20% scoring nodes on bridge strength (a cut-off recommended as giving an acceptable balance between sensitivity and specificity). Yellow nodes represent the bridge nodes. Orange nodes represent depressive items from the CDSS scale. Blue nodes represent 7 negative symptoms from the PANSS scale, and green nodes represent items from the PANSS positive scale. See Fig. 1 caption for node key.

12-month network

At 12-months, 50.02% of all possible edges were retained in the regularized network. Similar visualisations for baseline network can also be identified in the 12-month network, with strong positive associations between items as visualised in the baseline network (Fig. 1b ). Depression (C1) had the highest node strength in the 12-month network (Fig. 2 ). The top 20% bridge symptoms included: depression (C1), conceptual organisation (P2), stereotyped thinking (N7), hallucinatory behaviour (P3), and suspiciousness (P6). Similar to the baseline network, stereotyped thinking bridged with conceptual disorganisation, and the depressive items bridged with positive symptoms. Hallucinations and the suicide item were positively related, in addition to positive associations between observed depression with suspiciousness and hallucinations (Fig. 3b ).

Network comparison

Our results indicate that the baseline and 12-month networks differed significantly in overall structure (M = 0.16405, p  = <0.0001) and connectivity (S = 0.74536, p  = 0.02), but did not differ significantly in overall strength centrality and bridge centrality (C = 0.096153; p  = 0.22297).

The global strength and overall connectivity of the baseline network was stronger. Similarly, for the structure, the baseline network retained more edges than the 12-month network. Ten edges were significantly different across the baseline and 12-month networks. Excitement (P4) with emotional withdrawal (N2), delusions (P1) with lack of spontaneity (N6), hallucinatory behaviour (P3) with stereotyped thinking (N7), suspiciousness (P6) with depression (C1), excitement (P4) with guilt ideas of reference (C4), passive social withdrawal (N4) with pathological guilt (C5), pathological guilt (C5) with morning depression (C6), grandiosity (P5) with early awakening (C7), abstract thinking (N5) with suicide (C8), and depression (C1) with observed depression (C9).

Network accuracy and stability

The bootstrap analyses showed that the networks were very stable and edge weights were accurately estimated. The results for the edge weight bootstrap, edge weights significance testing, and strength centrality difference testing can be visualised in the supplementary material (Please see Fig. 1 – 6 in the supplementary material). For the subset bootstrap, the two networks showed acceptable centrality stability (Figures 7 and 8 in the supplementary materials). These results are consistent with the CS-coefficient, which was 0.75 for strength for the baseline network, and 0.75 for strength in the 12-month network, suggesting that the networks remained stable.

Sensitivity analyses

Because of the high level of missing data, sensitivity analyses were conducted using the complete cases ( N  = 718). The data are available in the supplementary material (Figures 9 – 19 ), but in sum, the baseline and 12-month networks remained dense (47% and 50.6%, respectively), and stable (0.75). Key central and bridge symptoms remained the same, though unlike the networks with imputed cases, the overall network structure and connectivity was not significantly different across the two time points.

This study presents the first analysis of symptom networks in a large, representative FEP sample, over two timepoints. Key findings were as follows: the networks differed significantly in terms of overall structure and connectedness, but central symptoms did not differ significantly. Depression featured consistently as a central symptom in the baseline and 12-month network. Conceptual disorganisation, stereotyped thinking, along with hallucinations and suspiciousness, remained key bridge symptoms across the networks.

It has previously been shown that network structures and connectedness differ for those in remission [ 15 , 17 , 19 ]. Within the present study, the difference in network structure and connectedness may reflect an improvement in symptoms by 12 months. However, interestingly, we showed that symptom centrality remained unchanged across the networks. Identifying key symptoms which become prominent in the networks over this critical illness period may serve as fruitful treatment targets to promote recovery.

Influential network symptoms

The emergence of depression as an influential symptom in the baseline and 12 month network is in line with an affective pathway to psychosis, where psychosis symptoms may result from heightened emotional reactivity [ 7 , 26 , 50 ]; potentially reflecting a continuation of a longstanding developmental trajectory [ 51 ]. Recent network studies add to this evidence, demonstrating that FEP is rooted in the context of both earlier sub-threshold symptoms as well as non-psychotic symptoms [ 51 ]. A recent cross sectional network study by Bet and colleagues also demonstrated that the relationship between adverse life events and psychosis symptoms was only present via general symptoms such as depression and guilt feelings [ 25 ]. Burden of recent life events predicted depression and guilt 3 months later, demonstrating the temporal relationship between life event burden and severity and persistence of affective psychopathology [ 25 ]. In the present longitudinal paper, the presence of central depressive symptoms early in the illness course may suggest that affective symptoms may underly the expression of other psychotic symptoms [ 52 ]. Though psychotic symptoms had significantly reduced by follow-up, the centrality of affective symptoms might mean that the network is descended into a state of vulnerability, where a potential worsening of depressive symptoms (e.g., triggered by a burdensome life event), may lead to a global worsening of psychosis symptoms.

An alternative explanation is that depressive symptoms may be secondary to the resolution of frank psychosis. Post-psychotic depression is prevalent following the initial episode and might account for the high rates of suicidality following FEP [ 8 , 53 ]. It often arises as a result of negative illness appraisals once insight is regained [ 8 ]. However, within our networks, depression remained a central symptom from baseline, and consistent bridge-symptoms between depression and psychosis symptoms were observed.

When bridge-symptoms are present, the likelihood of other communities of activated symptoms increases. Bridge-symptoms can help to explain the continuity and comorbidity of depression and psychosis [ 10 ]. Within this study, a bridge between hallucinations and suicide was consistent across the two time points. This complex interplay has been demonstrated previously; predominantly, suicidality is associated with auditory hallucinations [ 54 ]. We have shown that individuals with FEP and depression experience greater perceived malevolence in voices and greater engagement [ 8 ], and command hallucinations, where a voice is perceived as power and omnipotent, is associated with suicidal behaviour [ 55 ].

Within our networks, bridges also emerged between suspiciousness with depression and hopelessness; again, a phenomenon reported in prior research where those with

persecutory delusions encounter depression, especially when they feel less powerful than their persecutors [ 8 , 56 ]. This relationship is also replicated in previous network studies in males with schizophrenia, and recently in young people with FEP [ 15 , 27 ]. Here, these studies also showed depression as being intrinsic to psychosis symptoms. A longitudinal network approach comparing individuals across different illness stages would be necessary to establish the causal relationship between depression and the expression of psychosis symptoms.

Finally, it is also notable that conceptual disorganisation and stereotyped thinking, featured consistently as central and bridge symptoms in the networks. Formal thought disorder, which is characterised by disturbances in thought, language and communication [ 57 ], has been identified as a core feature in those with enduring illness and is linked to adverse outcomes, including: higher relapse and re-hospitalisation rates [ 58 ], and poorer social and occupational functioning [ 59 , 60 ]. Although the impact of thought disorder on illness manifestation in the early stages of illness is generally under-recognised, in a study of individuals at-risk of psychosis, those with disturbances in thought and communication were more likely to transition to psychosis and have poorer functional outcomes [ 61 ]. This may suggest that the emergence of thought and communication disturbances in early psychosis may be a marker of long-term poor outcomes [ 59 ]. Indeed, it has previously been proposed that thought disorder is a manifestation of a core deficit of ‘classical’ schizophrenia, characterised by pervasive brain changes, cognitive impairment, and entrenchment of poor functioning [ 62 , 63 ]. This psychopathological trajectory also invokes the idea of Hebephrenia, and the presence of these characteristic may indicate a more pervasive course of illness [ 64 ].

Implications

Identifying key central and bridge symptoms in developing psychopathology is potentially important, as they may activate other symptoms in the network, creating self-reinforcing feedback loops [ 15 ]. Targeting interventions at key symptoms may break down this maintenance cycle and provide a boost in momentum required for global improvement [ 4 ]. Symptoms of formal thought disorder (e.g. conceptual disorganisation, stereotyped thinking and excitement), in addition to depressive symptoms, showed prominence in the networks at baseline and follow-up; these symptoms may offer more refined targets for novel stratified treatments in early phases of psychosis. It is apparent that a number of individuals in FEP continue to have poor outcomes and remain unresponsive to ‘gold standard treatments’ [ 65 ]. Those with comorbid depression in psychosis are shown to have poor outcomes [ 66 , 67 ]. Conventional interventions for those with particularly complex symptom presentations, such as those presenting with early thought disorder, are also shown to be less effective [ 68 ]. This highlights the need for better recognition of these symptoms in early psychosis, in addition to improved, and stratified interventions for subgroups who are unlikely to respond to conventional treatments. Thus, a better understanding of the mechanisms by which these underrecognized early symptoms might facilitate change in the entire symptom network may prove beneficial [ 4 ]. Future work may seek to clarify whether network structures differ over time in those with and without a remitted status. This would provide clarity on the causality of network structures over time, and how this may relate to illness outcome and progression. Further research is also necessary to establish whether the influence of depression on psychosis symptoms is an integral feature of the illness, or whether it most prominent at particular time points, such as at 12 months, as we demonstrated within our networks.

Strengths and limitations

A strength of this study is the examination of a heterogenous sample from a large longitudinal national cohort of young people early in their illness course. In addition, we add to previous network studies in psychosis by including data from male and female participants at two time-points, and use novel statistics to compare network strength, centrality, and connectivity. Although we report on a large national sample of young people with psychosis, data were missing, and subsequently imputed for 23% of our sample. However, results of our sensitivity analyses showed consistent findings regarding network density, stability, and symptom centrality. A second limitation is that we did not include socio-demographic factors within our networks. Such factors (e.g. sex, age of onset, level of education) are shown to influence illness outcomes in schizophrenia, however, their influence on symptom expression remains inconclusive, particularly in the early phase of illness [ 69 ]. Two studies within FEP showed that despite differences between males and females on age of onset, premorbid functioning, and duration of untreated psychosis, there were no differences in symptoms severity at presentation [ 70 , 71 ]. Whilst this warrants investigation at a network level, inclusion of these factors within our network is beyond the focus of our research question. Third, we acknowledge that the group-level nature of our analysis does not allow for conclusions to be drawn on an individual level. And finally, though PANSS scores differed between the networks, overall, the scores are relatively low. Comparisons with network structures in those with more severe and enduring psychopathology, as well as those at clinical high risk of psychosis, may be more informative in understanding illness stage and progression. Within the current design, we were not able to establish whether depression emerges as prominent not just at 12 months, but potentially earlier, during the prodrome or sub-threshold stages.

We provide novel findings of symptom networks in early psychosis with robust data from a large longitudinal sample. Depressive symptoms, in addition to conceptual disorganisation and stereotyped thinking, which are often under-recognised in early psychosis, may potentially serve as novel symptom targets, which if adequately addressed, may have the potential to lead to global symptom improvements and better recovery.

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Acknowledgements

The National EDEN study was funded by the National Institute of Health Research (NIHR) under the Programme Grants for Applied Research (RP-PG-0109-10074). Birmingham and Solihull NHS Foundation Trust acted as study sponsor. M.B. and S.P.S are part funded by the National Institute for Health Research through the Applied Research Collaboration West Midlands (ARC-WM). P.B.J. is part funded by the NIHR ARC East of England. G.B. was supported by the University of Birmingham Department of Population Sciences and Humanities. S.P.L. is funded through a Clinical Academic Fellowship from the Chief Scientist Office, Scotland (CAF/19/04). The views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR, or Department of Health. We would like to thank the participants of the National EDEN study and the UK Clinical Research Network for study support.

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These authors contributed equally: Max Birchwood, Rachel Upthegrove

Authors and Affiliations

Institute for Mental Health, University of Birmingham, Birmingham, UK

Siân Lowri Griffiths, Pavan Kumar Mallikarjun & Rachel Upthegrove

Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK

Samuel P. Leighton

College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

Georgina Blake & Rachel Upthegrove

Birmingham and Solihull Mental Health Foundation Trust, Birmingham, UK

Linda Everard

Department of Psychiatry, University of Cambridge and CAMEO, Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK

Peter B. Jones

Department of Psychology, University of Sussex, Brighton, UK

David Fowler

Norwich Medical School, University of East Anglia, Norwich, UK

Joanne Hodgekins

Academic Unit of Psychiatry, University of Bristol, Bristol, UK

Institute of Clinical Trials and Methodology, University College London, London, UK

Nick Freemantle

Early Intervention Service, Cheshire and Wirral NHS Foundation Trust, Liverpool, UK

Vimal Sharma

Lancashire Care NHS Foundation Trust, Preston, UK

Max Marshall

Institute for Life Course Development, University of Greenwich, London, UK

Paul McCrone

Mental Health and Wellbeing Warwick Medical School, University of Warwick, Coventry, UK

Swaran P. Singh & Max Birchwood

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Contributions

The data were analysed by S.L., S.L.G., and R.U. S.L.G., R.U, S.L., and G.B. drafted the manuscript with further input from M.B. and P.K.M. M.B. was the CI and grant holder, J.H., L.E., P.B.J., D.F., T.A., N.F., V.S., S.P.S., P.Mc., and M.M. contributed to the EDEN study design and execution. All authors approved the final manuscript.

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Correspondence to Siân Lowri Griffiths .

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RU reports grants from Medical Research Council, grants from National Institute for Health Research: Health Technology Assessment, grants from European Commission—Research: The Seventh Framework Programme, personal fees from Sunovion, outside the submitted work. PM reports grant from the Medical Research Council, and has received honorariums from Sunovion, Sage and Recordati outside of the submitted work.

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Supplementary information

Figure 1. baseline bootstrapped ci of edge weights, figure 2. baseline bootstrapped difference tests for non zero edges, figure 3. baseline bootstrapped difference test between node strength, figure 4. twelve month bootstrapped ci of edge weights, figure 5. twelve month bootstrapped difference tests for non zero edges, figure 6. twelve month bootstrapped difference test between node strength, figure 7. baseline average correlations with sample case dropping bootstrapped, figure 8. twelve month average correlations with sample case dropping bootstrapped, figure 9. network visualisations for the sensitivity analysis, figure 10. strength centrality estimates for the sensitivity analysis, figure 11. top 20% scoring bridge nodes for the sensitivity analysis, figure 12. baselinebootstrapped ci of edge weights for the sensitivity analysis, figure 13. baseline bootstrapped difference tests for non zero edges for the sensitivity analysis, figure 14. baseline bootstrapped difference test between node strength for the sensitivity analysis, figure 15. baseline average correlations with sample case dropping bootstrap for the sensitivity analysis, figure 16. twelve month bootstrapped confidence intervals for the edge weights for the sensitivity analysis., figure 17. twelve month bootstrapped difference tests for non zero edges for the sensitivity analysis., figure 18. twelve month bootstrapped difference test between node strength for the sensitivity analysis, figure 19. twelve month average correlations with sample case dropping bootstrap for the sensitivity analysis, code final r, rights and permissions.

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Griffiths, S.L., Leighton, S.P., Mallikarjun, P.K. et al. Structure and stability of symptoms in first episode psychosis: a longitudinal network approach. Transl Psychiatry 11 , 567 (2021). https://doi.org/10.1038/s41398-021-01687-y

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Published : 06 November 2021

DOI : https://doi.org/10.1038/s41398-021-01687-y

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Early interventions to prevent psychosis: systematic review and meta-analysis

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This article has a correction. Please see:

• Errata - February 05, 2013
• Megan R Stafford , systematic reviewer 1 ,
• Hannah Jackson , research assistant 1 ,
• Evan Mayo-Wilson , senior research associate 2 ,
• Anthony P Morrison , professor of clinical psychology 3 ,
• Tim Kendall , codirector National Collaborating Centre for Mental Health 4
• 1 National Collaborating Centre for Mental Health, Royal College of Psychiatrists, London, UK
• 2 Centre for Outcomes Research and Effectiveness, Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
• 3 School of Psychological Sciences, University of Manchester, Manchester, UK
• 4 Sheffield Health and Social Care NHS Foundation Trust, Sheffield S10 3TH, UK
• Correspondence to: T Kendall tim.kendall{at}shsc.nhs.uk
• Accepted 8 January 2013

Objective To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay transition to psychotic disorders for people at high risk.

Design Systematic review and meta-analysis.

Data sources Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status.

Review methods Randomised trials comparing any psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising the results.

Results 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range 51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference −0.07 (−0.14 to −0.01). Very low quality evidence for omega-3 fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions in transition to psychosis at 12 months.

Conclusions Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis.

Introduction

The incidence of probable psychosis in community surveys in the United Kingdom appears to be stable, at about five per 1000 adults.[1] [2] Schizophrenia is the most common form of psychosis and one of the leading causes of long term disability,[3] affecting about 25 million people worldwide. Schizophrenia disrupts social and family relationships, resulting in severe educational and occupational impairment, lost productivity, unemployment, physical illness, and premature mortality.[4] As a result, schizophrenia costs about £55 000 (€67 500; $88 000) per person per year in the UK.[5]

Schizophrenia is usually preceded by a prodromal period lasting one to three years.[6] This period is characterised by a range of non-specific behavioural and psychological symptoms, functional deterioration, and by both attenuated positive symptoms and brief limited intermittent psychotic symptoms (BLIPS).[7] Among people at “ultra high risk” of psychosis, about 22% to 40% transition within 12 months.[8][9][10] Interventions that delay or prevent transition to psychosis from this prodromal syndrome could be clinically and economically important.

Antipsychotic drugs and family therapy could reduce the likelihood of relapse for established and first episode schizophrenia, and cognitive behavioural therapy (CBT) might reduce symptoms and hospital admission for people with schizophrenia.[11] Combining these treatments in an integrated strategy might add substantial clinical[12] and economic benefits[13] for people with psychosis and early schizophrenia. These interventions could prevent or delay the onset of psychosis and schizophrenia if delivered to people at high risk, and several trials have examined whether these interventions prevent transition from a high risk state to psychosis. A previous review of early interventions[14] found limited evidence about interventions to prevent psychosis, but the searches were conducted in 2009, and several studies conducted since then have been sufficiently large to change the review’s conclusions. An updated review is needed to determine whether any interventions can prevent or delay transition to psychotic disorders.

Eligibility criteria

We evaluated the effect of any intervention (pharmacological, psychological, nutritional, or combination) for participants with prodromal symptoms. Included participants were judged to be at risk of developing psychosis on the basis on a clinical assessment identifying prodromal features. Studies including participants with a formal diagnosis of schizophrenia or bipolar disorder (including first episode psychosis) were excluded. Randomised controlled trials for people at risk and for participants with schizotypal disorders were included.

Types of outcome measures

The primary outcome was transition to psychosis. Secondary outcomes were symptoms of psychosis (total, positive, and negative), depression, and mania; quality of life; weight; and discontinuation. Analyses were conducted for outcomes measured within six months of randomisation, between six and 12 months of randomisation, and after 12 months of randomisation.

Search strategy

We searched Embase, Medline, PreMedline, PsycINFO, and CENTRAL from the inception of the databases to November 2011. Searches in Embase, Medline, PreMedline and PsycINFO were combined with a highly sensitive filter for randomised controlled trials. The search was initially developed in Medline before being translated for use in other databases. The box details the Medline search for groups at risk (web appendix 1 shows the full list of search terms used across databases). We also searched the reference lists of included studies, excluded studies, and previous reviews, and contacted study authors and experts.

Medline search

1) exp psychotic disorders/ or “schizophrenia and disorders with psychotic features”/ or exp schizophrenia/ or schizophrenia, childhood/

2) (delusional disorder$ or hebephreni$ or psychosis or psychoses or psychotic$ or schizo$).ti,ab.

3) ((chronic$ or serious or persistent or severe$) adj (mental$ or psychological$) adj (disorder$ or ill$)).mp.

5) *risk factors/

6) (symptom$ or symptomology).sh. or (prodrom$ or risk$).hw.

7) (blips or brief limited intermittent psychotic symptom$ or ((attenuat$ or early or premonitory or pre monitory) adj2 (sign$ or symptom$)) or predelusion$ or prehallucin$ or prepsychos$ or prepsychotic$ or preschizo$ or (pre adj (delusion$ or hallucin$ or psychos$ or psychotic$ or schizo$)) or prodrom$ or subclinical$ or sub$ clinical$ or subthreshold$ or sub$ threshold$ or at risk$ or ((high$ or incipient or increas$) adj3 risk$)).ti,ab.

9) (conversion$ or ((develop$ or progress$) adj2 (psychos$ or psychotic$ or schiz$)) or first episode$ or fullthreshold$ or full threshold$ or onset$ or progression or transition$ or transitory).ti,ab.

10) 8 and 9

11) ultra high risk.ti,ab.

12) ((at risk or ((high or increase$) adj2 risk) or blips or brief limited intermittent psychotic symptom$ or ((attenuat$ or early or premonitory) adj2 (sign$ or symptom$)) or prodrom$ or subclinical$ or sub$ clinical$ or subthreshold or sub$ threshold) and (psychos$ or psychotic$ or schiz$)).ti. or ((at risk or ((high or increase$) adj2 risk) or blips or brief limited intermittent psychotic symptom$ or ((attenuat$ or early or premonitory) adj2 (sign$ or symptom$)) or prodrom$ or subclinical$ or sub$ clinical$ or subthreshold or sub$ threshold) adj3 (psychos$ or psychotic$ or schiz$)).ab.

13) 4 and or/5,10-12

Assessment of bias

Studies were assessed independently by two authors (MRS, HJ) using the Cochrane Collaboration risk of bias tool.[15] Disagreements were discussed with a third author (EM-W) and resolved by consensus. Each study was rated for risk of bias owing to sequence generation; allocation concealment; blinding of participants, assessors, and providers; selective outcome reporting; and incomplete data. Risk of bias for each domain was rated as high (seriously weakens confidence in the results), low (unlikely to seriously alter the results), or unclear.

Data management

Data extraction and risk of bias assessments were completed using an Excel spreadsheet. We collected data for time points and measures, recruitment, inclusion and exclusion criteria, age, sex, setting, and location.

Statistical analysis

For continuous outcomes, we calculated the standardised mean difference, Hedges g .[16] For dichotomous outcomes, an overall risk ratio was calculated. All outcomes are reported with 95% confidence intervals. Overall effects were calculated using a random effects model. Continuous effects were weighted by the inverse of variance; dichotomous effects were weighted using the Mantel-Haenszel method.[17] [18]

Missing data were noted for each outcome. When dropout was not reported, we contacted the authors. If both primary and secondary outcomes reported data for completers as well as controlled for dropouts (for example, data imputed using regression methods), we used the data controlling for dropout. We conducted sensitivity analyses for the primary outcome (transition to psychosis) when studies reported data for completers only.

Statistical heterogeneity was assessed by visual inspection of forest plots, by performing the χ 2 test (assessing the P value), and by calculating the I 2 statistic,[19] [20] which describes the percentage of observed heterogeneity that would not be expected by chance. If the P value was less than 0.10 and I 2 exceeded 50%, we considered heterogeneity to be substantial. Meta-analyses were conducted using RevMan.[21] Confidence in the results was assessed using the GRADE method,[22] which is a structured assessment of the quality of evidence attending to the following factors: risk of bias, inconsistency, indirectness, imprecision, and publication bias.

Of 1913 potentially relevant citations, we retrieved 39 papers; of these, 18 were excluded as they did not meet our eligibility criteria (web appendix 2). The most common reason for exclusion was that the study was not a randomised controlled trial. Eleven randomised controlled trials reported in 21 published papers met all inclusion criteria (fig 1 ⇓ ), and authors provided unpublished data for two of these.[23] [24]

Fig 1 PRISMA flowchart. *Number of records screened for eligibility for the guideline in which the current work was a part

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Study characteristics

Eleven included trials assigned 1246 participants with a median sample size of 81 (range 51-288). The median of the mean ages was 21 years, and 710 (57%) randomised participants were male. Eight studies[23][24][25][26][27][28][29][30] included participants meeting one or more of three operationally defined groups (attenuated psychotic symptoms, transient psychotic symptoms, trait and state risk factors). The first two groups were operationalised as scoring above a threshold on a screening instrument: the structured interview for prodromal symptoms,[9] the positive and negative symptom scale (PANSS)[31], the brief psychiatric rating scale (BPRS),[32] or the comprehensive assessment of at risk mental states (CAARMS).[33] One study included adults who met ICD-10 (international classification of diseases, 10th revision)[34] research criteria for schizotypal disorder,[35] two studies used the early recognition inventory (ERIraos),[36] with one study identifying participants in the early initial prodromal state[37] and one study not reporting the eligibility threshold used.[38] Table 1 ⇓ lists characteristics of the included studies.

 Characteristics of included studies

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The 11 included studies made eight comparisons. Four trials compared CBT with supportive counselling and monitoring.[23] [25] [28] [29] Two trials compared risperidone and CBT with supportive counselling.[24] [30] One trial each compared risperidone and CBT with placebo and CBT,[24] olanzapine with placebo,[27] integrated therapies with supportive counselling,[37] integrated therapies with standard treatment,[35] omega-3 fatty acids with placebo,[26] and amisulpride plus a needs based intervention with the needs based intervention alone.[38]

Trials of CBT[23][24][25] [28][29][30] provided manualised, problem focused, time limited treatments including normalisation, cognitive restructuring, and behavioural experiments. Supportive counselling and monitoring[23][24][25] [28] [30] [37] were designed to match interventions for non-specific effects of treatment, and included psychoeducation, referral, and crisis management. “Treatment as usual” for participants currently seeking help for mental health problems occurred in mental health services[29] or at a community mental health centre.[35] Integrated psychological therapies included CBT for individual patients, group skills training, cognitive remediation, and family treatments, with concomitant antipsychotic treatment[35] or without treatment.[39] In one study, the needs based intervention included usual clinical management and could include psychoeducation, crisis intervention, family counselling, and assistance with education or work related difficulties.[38] Web appendix 3 provides a detailed description of the psychological interventions used in the included trials.

Transition to psychosis was defined in several ways, including ICD-10[34] diagnosis of psychotic disorder[35]; diagnosis of schizophrenia spectrum disorders[25] using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)[40]; a measure developed by the authors[27]; PANSS[31] symptom severity[23] [26] and CAARMS[33] symptom severity[24] [28] [29]; and presence of positive psychotic symptoms.[30] One study assessed the transition from the early initial prodromal state to either the development of attenuated or transient symptoms (that is, subthreshold psychosis) or a DSM-IV psychotic disorder.[37]

Risk of bias

We rated risk of bias ratings for each trial (fig 2 ⇓ ) using the Cochrane risk of bias tool.[41] No trials were at high risk of bias for sequence generation (not truly random), however, the method of randomisation was unclear (not reported) in three trials.[27] [30] [38] Risk of bias owing to poor allocation concealment was unclear in four trials.[25] [27] [30] [38] Lack of blinding of assessors created a high risk of bias for some outcomes in three studies.[30] [35] [38] Eight studies were at high risk of bias because participants or staff were not blind,[23] [25] [28][29][30] [35] [37] [38] which was impossible for studies of psychological interventions.

Fig 2 Risk of bias

There was a high risk of bias due to incomplete outcome data for all included trials, which reflected a high rate of attrition in studies of this type of population rather than a methodological deficiency in the studies themselves.[6] [23][24][25][26][27][28][29][30] [35] [37] [38]. In one study, some participants were not followed up for the last 12 months (that is, those entering in the final year of the study), and missing data could not be calculated on basis of the number of participants randomised.[28] Only four studies were clearly free of selective outcome reporting[23] [28] [29] [38]; three trials did not report all outcomes,[26] [35] [37] and it was unclear whether four trials reported all outcomes.[24] [25] [27] [30]

This review included several small studies of pharmacological and nutritional interventions. Because of small numbers, we were unable to assess publication bias formally—that is, using a trim and fill analysis[42]—but previous reviews have shown that studies of such interventions for children have been systematically under-reported in mental health, and that effects have been systematically overstated and harms systematically underestimated as a result.[43] Most of these interventions were developed before the introduction of mandatory trial registration,[44] rules with which manufacturers might fail to comply.[45] Because one or two small unpublished studies would be sufficient to change our view of the relative benefits and harms of these interventions, we considered that there was a high risk of publication bias.

Quantitative data synthesis

We conducted meta-analyses for eight comparisons. One trial with three treatment groups was included in three pairwise comparisons.[24] We analysed transition to psychosis (table 2 ⇓ ); symptoms of psychosis and depression; quality of life; dropout; and where possible, side effects (web appendix 4). Some evidence indicated that transition can be delayed (table 2) in trials of CBT,[23][24][25] [28] [29] CBT and risperidone,[30] integrated psychotherapy,[35] [37] and omega-3 fatty acids.[26] However, confidence in these estimates ranged from moderate to very low.

 Summary of effects for transition to psychosis

Psychological and complex psychosocial interventions

Within the first six months of treatment, four studies comparing CBT with supportive counselling and monitoring[25] [28] [29] [46] reported that CBT did not reduce transition to psychosis (risk ratio 0.62 (95% confidence interval 0.29 to 1.31)). But trials included only 40 events (591 participants), and overall this evidence was of low quality. However, there was moderate quality evidence at 12 months indicating that more completers in the supportive counselling group transitioned to psychosis (0.54 (0.34 to 0.86); fig 3 ⇓ ), which remained significant in sensitivity analysis (0.64 (0.44 to 0.93)). At 18 months, there was low quality evidence that CBT is associated with fewer transitions (0.63 (0.40 to 0.99)), and the effect did not remain significant in sensitivity analysis (0.55 (0.25 to 1.19)).

Fig 3 Transition to psychosis for participants receiving CBT versus supportive counselling, (at 6-12 months; includes completers only). M-H=Mantel-Haenszel

Combined effects for positive symptoms of psychosis (fig 4 ⇓ ), depression, and quality of life were not significant at any time point, but there was only low quality evidence for all outcomes except for positive symptoms within six and 12 months. One study[29] reported secondary outcomes only for participants who had not transitioned to psychosis; participants with the most severe symptoms were omitted from these analyses. In sensitivity analyses excluding this study, there was a significant effect for positive symptoms (standardised mean difference −0.27 (95% confidence interval −0.47 to −0.06)), but effects for other outcomes remained non-significant. There was low quality evidence for total symptoms of psychosis and negative symptoms of psychosis, and effects were not significant. Dropout rates were similar between groups within the first six months (risk ratio 1.09 (0.88 to 1.35)).

Fig 4 Positive symptoms of psychosis for participants receiving CBT versus supportive counselling (at 6-12 months). IV=inverse variance

There was very low quality evidence for the benefits and harms associated with CBT and risperidone from two studies comparing CBT and risperidone with supportive counselling.[24] [30] Within the first six months of treatment, fewer people receiving CBT and risperidone transitioned to psychosis (risk ratio 0.35 (95% confidence interval 0.13 to 0.95)), but these trials included only 17 events (130 participants). The effect was no longer significant after 12 months (0.63 (0.33 to 1.21); fig 5 ⇓ ) or after 36 months (0.59 (0.34 to 1.04)). There were no significant effects of this treatment on quality of life, symptoms of psychosis (total, positive, or negative), depression, or mania. Within six months, there were no dropouts in one study,[30] and the dropout rate in the second study[24] was similar between groups (0.76 (0.28 to 2.03)).

Fig 5 Transition to psychosis for participants receiving CBT and risperidone versus supportive counselling (at 6-12 months; includes completers only). M-H=Mantel-Haenszel

There was evidence of very low quality for the benefits and harms associated with integrated psychotherapy from one study[39] comparing integrated psychotherapy (mean number of sessions 15.8 (standard deviation 6.8)) with supportive counselling (23.7 (13.1)) in participants in the early initial prodromal state.[37] This study measured transition to an ultra high risk or high risk mental state or a DSM-IV psychotic disorder. Within the first 12 months, fewer people completing integrated psychotherapy transitioned to an ultra high or high risk mental state or to psychosis (risk ratio 0.19 (95% confidence interval 0.04 to 0.81)), but there were only 13 events (125 participants). The effect was maintained at 24 months (0.32 (0.11 to 0.92)). Dropout was similar between groups at 12 months (1.55 (0.68 to 3.53)) and 24 months (0.95 (0.61 to 1.49)).

There was low quality evidence from one study comparing integrated psychotherapies with standard treatment.[35] Within 12 months, fewer people receiving integrated psychotherapy transitioned to psychosis (risk ratio 0.24 (95% confidence interval 0.07 to 0.81)), but there were only 13 events (67 participants). The effect remained large when we assumed that dropouts transitioned (0.41 (0.20 to 0.85)), but the effect was not quite significant after 24 months (0.52 (0.26 to 1.02)). There was no effect for positive or negative symptoms of psychosis at either time point. Dropout was similar between groups at 12 months (0.63 (0.22 to 1.81)) and 24 months (0.66 (0.25 to 1.73)).

Pharmacological interventions

One study compared CBT and risperidone with CBT and placebo.[24] Very low quality evidence within the first six months of treatment suggested no difference in transition to psychosis (risk ratio 1.02 (95% confidence interval 0.15 to 6.94)), which remained at 12 months (1.02 (0.39 to 2.67)). Differences in symptoms of psychosis (total, positive, or negative), depression, and quality of life were not significant. Dropout was similar between groups (1.09 (0.62 to 1.92)), although the evidence was also rated as very low quality.

There was very low quality evidence for the benefits and harms associated with olanzapine, from one study comparing olanzapine with placebo.[27] We saw no difference in transition to psychosis after 12 months (risk ratio 0.44 (95% confidence interval 0.17 to 1.08)). Dropout was similar between groups at 12 months (1.59 (0.88 to 2.88)). For participants taking olanzapine, there was a large effect on weight during the first eight weeks (standardised mean difference 0.81 (0.28 to 1.34)), which remained large at 12 months (1.18 (0.62 to 1.73)). Effects on symptoms of psychosis (total, positive, or negative), depression, and mania were not significant. Data at 24 months were not analysed because fewer than 50% of participants remained.

We also found very low quality evidence for the benefits and harms associated with amisulpride, from one study comparing amisulpride and a needs based intervention with the needs based intervention alone.[38] Transition was not reported. Within six months, effects on total and negative symptoms of psychosis were not significant, but amisulpride was associated with a moderate reduction in positive symptoms (standardised mean difference −0.53 (95% confidence interval −0.93 to −0.13)), and depression (−0.51 (−0.91 to −0.11)). The addition of amisulpride was associated with a moderate reduction in dropout (risk ratio 0.59 (0.38 to 0.94)).

Nutritional supplements

We found low quality evidence for the benefits and harms associated with omega-3 fatty acids, from one study comparing omega-3 fatty acids with placebo.[26] Participants received treatment for 12 weeks, which was associated with a large reduction in transition to psychosis after treatment (risk ratio 0.13 (95% confidence interval 0.02 to 0.95)), but there were only nine events (76 participants). Assuming participants who dropped out transitioned to psychosis, the effect remained large at 12 weeks (0.39 (0.13 to 1.14)). This effect remained significant after 12 months (0.18 (0.04 to 0.75)), although the number of events was only 13 (81 participants). Treatment effects on total symptoms of psychosis (standardised mean difference −1.26 (−1.74 to −0.78)), positive symptoms (−2.08 (−2.63 to −1.54)), negative symptoms (−2.22 (−2.77 to −1.66)), and symptoms of depression (−0.56 (−1.01 to −0.12)) also favoured omega-3 fatty acids after 12 months. Dropouts at the end of treatment were not reported; however, dropout after 12 months was low and similar between groups (risk ratio 1.46 (0.26 to 8.30)).

Comparison with other studies

This systematic review and meta-analysis of treatments for people at high risk of developing psychosis included 11 trials and 1246 participants seeking treatment. Participants received a range of psychological, pharmacological, nutritional, and complex psychosocial interventions. This review included twice the number of studies and participants as a previous review, which did not find clear evidence of benefit.[14] Recent studies have contributed to a much larger dataset, which suggests that transition to psychosis from a high risk mental state could be preventable. These findings also suggest the future research strategies that are most likely to be fruitful, highlighting treatments that have the most potential for reducing transition to psychosis. On the basis of this review, further research is clearly warranted to determine the benefits of both psychological interventions—especially CBT with or without family treatment and a nutritional additive (omega-3 fatty acids).

Summary of results

Overall, five trials of CBT had a moderate effect on transition to psychosis at both 12 and 18 months. In sensitivity analyses, assuming dropouts had transitioned, the effect of CBT on transition remained significant at 12 months; however, the effect at 18 months was no longer significant. There has also been evidence that complex psychosocial interventions could reduce transition or delay onset of psychosis, relative to supportive counselling or treatment as usual. For omega-3 fatty acids, low quality evidence suggests a beneficial effect for a 12 week course of nutritional supplementation compared with placebo. However, the data emerged from a single trial with few participants, and this result has never been replicated to our knowledge. Although the absolute effects of treatments will vary across populations with different risks of psychosis at baseline (table 3 ⇓ ), effects for the most promising interventions are likely to be clinically meaningful for many psychiatric services.

 Absolute effects of treatments for patients at high risk and very high risk of developing psychosis. Data are number of participants per 1000 who will transition

Although no other treatments showed any clear or reliable effects, most of the studies included in this review had several problems. Many trials were at an unclear risk of selection bias, and some trials were rated as having high risk of detection bias. We considered it unlikely that blinding of participants or providers would introduce any important bias, and we did not downgrade for this reason. It is possible to blind assessors in studies of psychological interventions, and we considered that any lack of assessor blinding could introduce bias and contribute to downgrading our quality assessment. Only four studies were clearly free of selective outcome reporting, with several studies not reporting all outcomes.

All identified trials were at a high risk of bias owing to incomplete outcome data; however, this result reflected a high rate of attrition in studies of this type of population rather than a methodological deficiency in the studies themselves. In addition, the definitions of prodromal, high risk, and ultra high risk mental states varied between studies. One study[37] used the development of subthreshold psychosis (or “ultra high risk” mental state, which was the entry criteria for most of the other studies) as part of their primary outcome. Although broadly similar, the different entry criteria and operational definitions of transition to psychosis could account for the overall transition rates being lower than expected; therefore, caution should be exercised when interpreting our results. Similarly, epidemiological issues related to sampling, temporal fluctuation in symptoms, and risk enrichment strategies used in these trials, which would pose problems for the generalisability of these findings to routine healthcare settings.

Although most of the interventions used have some evidence for effectiveness in populations with frank psychosis, the included studies used different comparators, limiting comparisons between treatments and meta-analysis. Furthermore, control conditions that include active interventions could underestimate the effect of some interventions relative to no intervention. For example, comparisons included combinations of supportive counselling, regular and frequent monitoring of mental states, and treatment as usual. Consequently, transition at 12 months ranged from 7.1%[28] to 27%.[30] Additionally, 25% of participants in one study were inpatients at baseline,[35] suggesting an already ill population, perhaps even having already transitioned to psychosis, or representing people at high risk of self harm. Moreover, most studies recruited people who were seeking treatment, which necessarily omitted people who could benefit from help but did not seek it.

Our analyses were sensitive to assumptions about dropouts. Analyses of study completers suggest that psychological interventions (CBT with or without family intervention) have a beneficial effect; however, some findings were not significant when dropouts were assumed to have made transition. Since transition to psychosis is probably associated with service use, and most trials traced participants lost to follow-up via health records and family doctors, completer analyses (which are similar to analyses assuming that dropouts did not transition) might accurately represent participant outcomes. Because most outcomes were reported within one year, we considered the simple dichotomous outcome to be the best at measuring time to transition. Time to transition was measured and reported in several ways that would not facilitate a meaningful and transparent synthesis or a sensitivity analysis to test the importance of assumptions about dropouts.

Strengths and limitations of study

Our choice of primary outcome (dichotomous transition to psychosis) reflects the primary outcomes used in the clinical trials. However, it has been argued[47] that this crossing of a threshold is arbitrary and overemphasises the importance of positive symptoms, and that other dimensions might be more informative, such as negative symptoms, functioning, and quality of life. Therefore, we also analysed these outcomes, but fewer trials reported these variables and our analyses are probably underpowered as a result.

Importantly, we found no evidence to support the early promise of some antipsychotic drugs in delaying or preventing transition to psychosis. In addition, antipsychotic drugs are associated with clinically significant side effects. Although this is best described as an absence of evidence rather than evidence of absence, this review identifies no reason to pursue this line of enquiry. Many people at ultra high risk will not progress to psychosis, and we expect that any evidence indicating that the benefits outweigh the harms in this population would have been published. Furthermore, in a recent study of young people at risk of developing psychosis enrolled in a psychosocial treatment programme, significant clinical improvements were found without the use of antipsychotic drugs.[48]

Psychological treatments are also associated with significant side effects, with about 10% of participants in such treatments deteriorating,[49] [50] but psychological therapies are unlikely to cause the harms associated with antipsychotic drugs. Psychological treatment might be associated with an increase in stigma and other consequences for participants who would not develop psychosis even without treatment. Furthermore, there are ethical considerations in the delivery of all interventions for this population. Any future trials of psychological interventions should measure and report such adverse effects.

Directions for future research

The findings of this review do suggest two possible directions for future research. Firstly, the results of the trial using omega-3 fatty acids suggest that this intervention might have a beneficial effect on transition rates. A replication study with a larger sample is needed to determine whether this intervention has any merit. The use of omega-3 fatty acids is a relatively safe treatment with few health risks that could have other potential benefits (such as for cardiovascular status).[51] Therefore, this intervention has particular appeal.

The second approach is based on the possible benefits from CBT, with or without family intervention. Good evidence indicates that family interventions are effective in reducing relapse rates in first episode psychosis and in established schizophrenia; and there is evidence that individual CBT has symptomatic benefit in both these contexts.[11] Preliminary evidence also indicates that cognitive therapy could benefit patients with first episode psychosis in the absence of antipsychotic drug treatment.[52] Moreover, the strongest evidence for prevention of recurrent psychotic episodes is for family interventions rather than individual CBT.[11] Transition from a high risk state to a first episode of psychosis might be susceptible to a treatment strategy combining family and individual CBT.

CBT may be particularly appropriate in light of the high prevalence of anxiety and mood disorders in this population.[28] [30] That is, guidelines for treatment of anxiety and depression recommend individual CBT, suggesting that CBT might also be helpful to patients who present in services but who will never transition to psychosis. Consideration of how to deliver these psychological interventions in an accessible and timely manner is required. Considerable investment would probably be needed in training therapists in this approach, or innovative methods need to be developed and evaluated. In the UK, it may be possible to incorporate this approach within the existing Increasing Access to Psychological Therapies programme, which has recently been extended to include children and young people as well as adults. To overcome some of the epidemiological issues outlined above, treatments could be embedded within a general staging model of mental healthcare. This model aims to deliver preventative, early interventions to young people in the hope of avoiding the development of more severe disorders.[53]

Conclusions and policy implications

Schizophrenia and the psychoses are highly disabling, recurrent, and most often lifelong conditions with substantial costs to the patient, their family, and the state—arguably greater than almost all other psychiatric conditions. The possible prevention of transition to psychosis and schizophrenia for people at high risk clearly represents an important finding.[54] Therefore, further research should be undertaken in the form of a large, multicentre trial of combined family and individual CBT for high risk groups, evaluating both benefits and potential harms (for example, possible increased stigma). In the meantime, the use of these psychological treatments now represents the most appropriate intervention available for helping people avert what could be a personal, social, and financial catastrophe.

What is already known on this topic

Schizophrenia is the most common psychosis and interferes with relationships, education, and occupational functioning

Schizophrenia is usually preceded by a prodromal period, and it has been shown that 22-44% of people at ultra high risk will transition to develop schizophrenia

Psychological or pharmacological interventions that delay or prevent transition from this prodromal period could be clinically and economically important

What this study adds

This meta-analysis suggests that there are interventions that could prevent psychosis

Individual cognitive behavioural therapy, with or without family CBT, could be the most sensible first line treatment for people at a high risk

Further research is needed to establish the potential benefit of psychological interventions for people at high risk of psychosis

Cite this as: BMJ 2013;346:f185

Contributors: All authors contributed to the development of the review questions. MS and EMW drafted the protocol. Sarah Stockton of the National Collaborating Centre for Mental Health) designed and implemented the searches. MS, HJ, and EMW assessed the eligibility of the studies for inclusion, extracted data, assessed risk of bias, and applied the GRADE criteria. All authors contributed to the analysis. All authors contributed to writing the manuscript, agreed on the final draft, had full access to the data (including statistical results and tables), and take responsibility for the integrity of the data and accuracy of the analysis. TK is the guarantor.

Funding: The National Collaborating Centre for Mental Health receives £1.4 million per year from the National Institute for Health and Clinical Excellence to develop guidelines for the treatment of mental health problems.

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from the National Institute for Health and Clinical Excellence for the submitted work; TK is codirector of the National Collaborating Centre for Mental Health; this work was conducted as part of a guideline about psychosis in children and young people, and the full review protocol is available from the authors; AM was an author of two studies included in this review.

Ethical approval: None required.

Data sharing: No additional data available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode .

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• Open access
• Published: 02 November 2023

Borderline personality disorder and early psychosis: a narrative review

• Arianna Biancalani 1 ,
• Lorenzo Pelizza 1 &
• Marco Menchetti 1  

Annals of General Psychiatry volume  22 , Article number:  44 ( 2023 ) Cite this article

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The purpose of the present review was to summarize the main literature contribution on the relationship between borderline personality disorder (BPD) and early psychosis. While retracing the historical path of the term “borderline”, specific attention was paid to psychotic and psychotic-like symptoms in BPD. Its relationship with At Risk Mental State was evaluated, as well.

This search was conducted on PUBMED/MEDLINE and PsycInfo, looking for “Borderline personality disorder, First Episode Psychosis, Early Psychosis, Ultra-High Risk AND/OR Clinical High Risk” for psychosis.

Eight pertinent papers were identified on this topic. Their main findings were then discussed. The term “borderline” has undergone different changes in meaning and use, despite always referring to states considered on the fence between neurosis and psychosis. However, considering the history of psychopathology and its relationship with diagnostic manuals, little attention has been given to its psychotic features. Being those symptoms highly burdensome, this neglect has often led to misdiagnosis and under-treatment.

Conclusions

Psychotic symptoms in BPD can be severe and distressing. Nonetheless they can be easily neglected, and when found they challenge clinicians in defining a differential diagnosis to distinguish between BPD and Psychosis Spectrum Disorders. Given specific needs and interventions for these different conditions, a dimensional, rather than categorical, approach should be considered, as well as specific care pathways and monitoring should be advised.

History of the concept of “Borderline” disorder

For over a century, since it was first used as a psychoanalytic concept by Stern in 1938 [ 1 ], the term “ borderline ” has experienced a continuous change in use and understanding. In this respect, Stern originally used the word to describe a cluster of patients who were not likely to respond well to psychoanalytic therapy and that he believed was somehow different both from schizophrenia and neuroses [ 2 ]. In 1952, Knight [ 3 ] was the first to define a “borderline state”, which was conceptually very close to schizophrenia, but also had neurotic features and identified a temporary “ego state” that the patients could enter and exit, thus being affected only for a given time. This idea interestingly resembles a previous one by Zilboorg [ 4 ], a psychoanalyst who at first described patients with “ambulatory schizophrenia”, in which it was reported one of the two main roots of the “borderline” concept: i.e., its psychotic features (shared with schizophrenic disorders).

It was in 1967, then, that the term predominantly ceased to identify a mild form of schizophrenia, when Kernberg [ 5 ] borrowed it to describe one of the possible levels of personality organizations (namely, “psychotic”, “neurotic” and “borderline”). Quite differently from what Stern had stated, Kernberg used it to qualify a disorder not likely to change during time and closer to our understanding, as well [ 6 ].

In the first edition of “A Glossary of Psychoanalytic terms and Concepts” [ 7 ], Moore and Fine defined “borderline” as “a descriptive term referring to a group of conditions which manifest both neurotic and psychotic phenomena without fitting unequivocally into either diagnostic category”. It is probably because of this indefiniteness that, despite the many attempts to classify it, it has always remained vague and hardly harmonized in the psychiatric field.

After a long journey through different schools of thought, where a “Borderline Syndrome” [ 8 ] and a “Borderline Disorder” [ 9 ] were described, in 1979 Spitzer and Endicott theorized the belonging of the “borderline patient” (as it was commonly perceived) either to a Schizotypal Personality Disorder or to an Unstable Personality Disorder [ 10 ]. Indeed, even if the term “borderline” had been misused for decades, there was no official description in any previous diagnostic manual. These two terms referred to the two main uses of the word “borderline”, identifying, on one hand, a group of patients more closely related to schizophrenia, and a group of patients predominantly characterized by “unstable affect, interpersonal relationships, job functioning, and sense of identity” [ 11 ]. Later, the task force who worked at the third edition of the Diagnostic and Statistical Manual of mental disorders (DSM-III), replaced the term “unstable personality disorder” with “borderline personality disorder”, which was clinically much more usual and wasn’t subject to misinterpretation on the actual stability of personality disorders. Despite Spitzer and Endicott [ 10 ] remarked how not mutually exclusive the two diagnoses were, but dimensionally likely to be integrated, psychotic-like features formally ceased to be associated with Borderline Personality Disorder (BPD) (for a brief summary of the history of BPD concept, see Table 1 ) [ 12 , 13 , 14 , 15 ].

Defining psychotic symptoms in BPD

According to the fifth edition of the Diagnostic and Statistical Manual of mental disorders (DSM-5), BPD is described by nine different criteria [ 16 ]. Notably, the ninth point mentions “transient, stress-related paranoid ideation or severe dissociative symptoms”, which somehow recalls the historical ambivalence of BPD psychopathology, considered on the fence between psychotic and neurotic symptoms [ 17 ]. However, psychotic features have not always been this relevant. It was only in 1994, when the DSM-IV was published, that BPD was acknowledged again a reference to potential psychotic experiences, after being strictly set apart from the schizotypal personality disorder in DSM-III [ 18 ].

For the first time in the history of The International Classification of Diseases and Related Health Problems, the 11 th revision (ICD-11) includes a description of psychotic-like symptoms “in situations of high affective arousal”, when identifying a borderline pattern for personality disorders [ 19 ].

Even if what should or should not be included in the description of BPD could seem only a theoretical issue, it is evident how the accuracy of definitions and criteria can affect the quality of diagnosis [ 20 ]. Also, even if the debate around the appropriateness of considering psychotic aspects a core diagnostic feature is still open, it is unarguable that these symptoms can be serious for patients who experience them [ 21 ]. What is needed, then, is an effective effort to address patients’ needs and to improve specific treatments, accordingly.

Evaluating the burden: the data so far

Psychotic symptoms in BPD are often underrated and considered temporary or mainly associated with stress [ 17 ]. Yet, going deeper into the study of their phenomenology and comparing them to the “proper” psychotic features of schizophrenia, similarities and differences depict a very specific pattern of characteristics.

On one hand, psychotic symptoms in BPD seem to be phenomenologically very similar to those experienced by patients with psychosis spectrum disorders [ 17 , 22 ]. As a direct consequence, differential diagnosis can be a challenge, thus leading to potential fluctuations in diagnosis and to mistreatment [ 23 ]. Also, despite the usual underestimation of psychotic experience in BPD, these symptoms can cause an extremely high burden. Among the most distressing psychotic symptoms in BPD, auditory verbal hallucinations (AVH) play a central role [ 21 ] and up to 50% of patients report them [ 24 ]. Indeed, some of the most worrying data suggest that AVH in BPD are associated with increased suicidal ideation, suicide attempts and hospitalizations [ 18 , 22 , 25 ]. If compared to those in schizophrenia, AVH in BPD have not been found to differ in frequency, duration, location, loudness, or conviction [ 17 ]. Coherently, misdiagnosis mostly happens when AVH differ from the common understanding of the diagnostic manuals and either meet criteria for “First Rank Symptoms” (FRS), and are perceived as coming from outside the head or when of lasting duration [ 20 ].

On the other hand, psychotic symptoms differ in some ways between BPD and Psychosis Spectrum Disorders. First, delusions, conceptual disorganization and negative symptoms seem not to be as common as in schizophrenia [ 17 ]. When describing AVH, patients with BPD refer a greater distress and negativity in content, yet they seem to be able to manage them better than patients with schizophrenia can, where commentary voices are also more frequent [ 17 ]. Given that AVH usually appear earlier in BPD (mean age at onset = 16 years) [ 22 ] and that these patients show better resistance, early diagnosis becomes fundamental in preventing the worsening of the symptoms and in aiming at the best possible quality of life.

Interestingly, a recent study [ 22 ] compared psychotic symptoms in adolescents with a full-criteria diagnosis of BPD to those experienced by subthreshold BPD patients. The main differences, concerning psychotic symptoms, psychoticism and occupancy, were observed between the full-threshold group and the subthreshold group. Despite the awareness that psychotic symptoms are always a risk factor for worse functioning, regardless of the diagnosis, this finding suggests that a diagnosis of BPD should be a hint for careful management and monitoring.

After defining the significance of psychotic symptoms in BPD, questions around treatment and management arise. There are many reasons why there is a high need for studies to assess the benefit of psychotherapy and antipsychotics in these specific cases [ 22 ]. One of the most relevant is the understanding that neurocognitive impairment is known to be greater in BPD with psychotic features [ 26 ]. One of the hypotheses is that such impairment can compromise mentalization, which consequently makes social cognition weaker and psychotic symptoms (starting with paranoid phenomena) more likely to arise. The use of antipsychotic drugs, which a recent review [ 27 ] reported to be effective in these patients, should also be furtherly discussed. As analyzed in a review by Beatson [ 20 ], the most studied antipsychotics for AVH in BPD are olanzapine (2.5–10 mg daily), aripiprazole (2.5–10 mg daily) and quetiapine (50–150 mg daily). Additional results about the efficacy of aripiprazole compared to placebo on AVH in young patients (aged 15 to 25 years old) are awaited soon, since a RCT on the topic is on its way to be published [ 28 ].

BPD in at-risk mental states and first-episode psychoses

Given the challenge of differentiating BPD with psychotic features from psychosis spectrum disorders, it is evident that this becomes even more difficult when subtle, subthreshold psychotic symptoms are involved (Table 2 ). Indeed, since transient psychotic symptoms can be present in both BPD and early psychosis, there is a significant overlap between “At-Risk Mental States” (ARMS) and BPD spectrum psychopathology with attenuated psychotic features at presentation [ 23 ].

Starting from this background, the aim of this narrative review was to examine the main findings on BDP in patients with early psychosis reported in the literature to date.

Methodology

The search was conducted on MEDLINE/PubMed and psycInfo, looking for “Borderline personality disorder, First Episode Psychosis, Early Psychosis, Ultra-High Risk AND/OR Clinical High Risk” for psychosis. We specifically analyzed papers written in English and published by May 31, 2023. We found 8 pertinent papers on this topic. Their main findings were reported and discussed (see Table 2 for details) [ 29 , 30 , 31 , 32 , 33 , 34 ].

Clinical similarity on such psychotic features can be possibly explained going deeper into the study of psychopathology. According to a study by Zandersen and Parnas [ 35 ], most patients with BPD (considering different stages of illness) meet criteria for a schizophrenia spectrum disorder (which includes Schizotypal Personality Disorder). This observation gives space to different thoughts. First, as it is known from a historical perspective, the choice to differentiate BPD from SPD has long been debated, since many patients often meet both criteria. All things considered, it is logical to assume that BPD as a concept ends up being over-inclusive [ 36 ]. This comes as a direct consequence of a methodological shift, which comprises the use of an atheoretical diagnostic manual, based on behaviors rather than personality structure and prototypes [ 35 ]. In addition, time should be taken to reflect upon the psychopathological concept of BPD and consider a step “back” to a theoretical understanding of the disorder, which was originally very close to schizophrenia. Specifically, there are some key BPD features, like “identity disturbance” and “feeling of emptiness”, which might resemble other symptoms, nonetheless belonging to the Schizophrenia Spectrum Disorders [ 35 ], like the so-called “disorders of the self”. Given the similarity, it would be helpful to build back awareness around the meaning DSM criteria have on a “narrative level” [ 35 ] and how deeply these concepts can be explored on a “core” psychopathological level. Differential diagnosis would then be easier. Also, this would allow the acknowledgment of those highly severe cases of BPD, who share a common psychopathological ground with schizophrenia. Interestingly, some effort has been made to determine whether different subgroups of BPD could explain its heterogeneity. Smits and co-workers [ 37 ], for instance, identified three clusters of BPD patients sharing common characteristics. Among these, a schizotypal/paranoid type was described as very close to SPD, with introjective and psychotic-like features, which inevitably posed questions around its risk for psychosis. This subgroup was not as represented as the Core BPD and the Extravert/Externalizing subtypes in the study, yet seemed to be more likely to present late at mental health services, thus being more vulnerable to negative outcomes.

So far, when examining ARMS, no predictive meaning towards transition to psychosis has been found in those patients who presented BPD symptoms [ 33 ]. Nonetheless, the severity of BPD psychopathology hasn’t been associated either with clinical higher or lower risk for psychosis, thus suggesting how every patient with BPD having attenuated psychotic symptoms and/or meeting cognitive-perceptive basic symptoms criteria (i.e., COGDIS and COPER) should be monitored, regardless of the scores [ 31 , 33 ] (see also Table 2 , for details on main empirical findings about BPD psychopathology in early psychosis). Then, this is even more important, since it is known that, while keeping in mind that not all people with BPD need to be screened for psychosis, their co-occurrence results in a worse functioning and response to treatment [ 38 ]. Indeed, a possibility of co-occurring diagnoses of BPD and schizophrenia spectrum disorder may also occur. In this respect, Bahorik and Eack [ 38 ] reported that at 1-year follow-up, patients with schizophrenia and comorbid BPD showed significantly less improvement in psychiatric symptomatology (particularly hostility and suspiciousness), as well as global functioning, and were re-hospitalized at significantly higher rates than individuals without BPD. The authors suggested that the co-occurrence of schizophrenia and BPD was not infrequent and that BPD had a significant negative longitudinal impact on the course and outcome of subjects with schizophrenia.

When it comes to analyzing the impact of BPD on First Episode Psychosis (FEP), recent findings suggest how the overlap of the two disorders can lead to an increased risk for depression and self-harm [ 34 ]. Surprisingly, despite a higher severity, this combination is not associated with a major number of hospitalizations. One possible explanation is that patients with BPD may undergo a substantial under-treatment, probably due to a common underestimation of their symptoms.

Considering that, according to Francey and colleagues [ 32 ], the subgroup of patients presenting with FEP and BPD can represent up to a quarter of the total cases of FEP, specific attention should be paid to the treatment. The same study reports how this cluster of patients is more likely to receive a lower dosage of antipsychotics. This finding underlies how specific guidelines would be helpful in avoiding a stigmatizing approach and consequent mistreatment.

BPD psychopathology can be found in patients presenting with early psychosis. Also, psychotic, or psychotic-like symptoms can be the main features already at the first contact of BPD patients with mental healthcare services. These statements lead to two main clinical considerations. First, personality structure and pathology should be explored in people presenting with early psychosis, since it is known personality disorders can hide specific needs and affect the response to treatment. This may also require developing new clinical guidelines and effective treatments for young patients with early psychosis and co-occurring BPD that take into account “premorbid” and interpersonal aspects of their presenting problems. Secondly, special attention should be paid to BPD patients who carry a high burden of disease, with intense psychological suffering and bad functioning. Indeed, the severity of symptoms and functional impairment should alert mental healthcare professionals and lead to a further investigation of basic symptoms and potential psychotic psychopathology (either attenuated or full-blown). In this respect, psychotic symptoms can be viewed as “trans-diagnostic phenomena” [ 39 ], with psychotic experiences in schizophrenia spectrum disorders and BPD sharing similarities, which raises the question of whether they are underlain by the same neural mechanism [ 40 ] and have common risk factors (such as previous traumatic events, family history of psychotic disorder, substance misuse) [ 41 ]. Taking this into account, theoretical questions around how BPD should be defined and perceived inevitably arise. Should BPD meeting psychotic symptoms or ARMS criteria be considered more severe and worthy a personalized approach? If so, should psychotic experiences be reconsidered as core diagnostic criteria? Since definitions do not always meet the reality of everyday clinical practice, what, anyhow, should be achieved is the understanding of the high suffering this kind of patients can go through. Moreover, the evidence that BPD patients with psychotic signs are often at higher risk of developing a wider range of negative outcomes (including suicidal thinking and behavior) cannot be ignored, especially when considering treatment and monitoring.

In conclusion, sometimes understanding this specific vulnerability requires mental health professionals to go beyond narrow diagnostic categories and embrace what is known as a “dimensional approach” to psychopathology and psychiatric disorders. Future studies on early psychosis and BPD should thus recognize both the dimensional and dynamic nature of psychopathological symptoms and evolving phenotypes across the transition from childhood to adulthood by adopting a clinical staging approach [ 42 ]. Such an approach needs to include the measurement of personality pathology, in order to focus on the etiological factors and treatment options for psychotic symptoms in BPD. Also, taking into account a “network approach to psychopathology” [ 43 , 44 ], common risk factors, such as trauma and substance abuse, could be considered as possibly interacting with each other, thus concurring to overlapping psychopathological categories. This could be the first step in the complex path to better understand the relationship between psychosis spectrum disorders and psychotic experiences being found in severe personality disorders.

Availability of data and materials

Not applicable.

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Biancalani, A., Pelizza, L. & Menchetti, M. Borderline personality disorder and early psychosis: a narrative review. Ann Gen Psychiatry 22 , 44 (2023). https://doi.org/10.1186/s12991-023-00475-w

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The lived experience of psychosis: a bottom‐up review co‐written by experts by experience and academics

Paolo fusar‐poli.

1 Early Psychosis: Interventions and Clinical‐detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London UK

2 OASIS service, South London and Maudsley NHS Foundation Trust, London UK

3 Department of Brain and Behavioral Sciences, University of Pavia, Pavia Italy

4 National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley, London UK

Andrés Estradé

Giovanni stanghellini.

5 Department of Psychological, Territorial and Health Sciences, “G. d'Annunzio” University, Chieti Italy

6 Center for Studies on Phenomenology and Psychiatry, Medical Faculty, “D. Portales” University, Santiago Chile

Jemma Venables

7 South London and Maudsley NHS Foundation Trust, London UK

Juliana Onwumere

8 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London UK

9 Bethlem Royal Hospital, South London and Maudsley NHS Foundation Trust, Beckenham UK

Guilherme Messas

10 Mental Health Department, Santa Casa de São Paulo School of Medical Sciences, São Paulo Brazil

Lorenzo Gilardi

11 Como, Italy

Barnaby Nelson

12 Orygen, Parkville VIC, Australia

13 Centre for Youth Mental Health, University of Melbourne, Melbourne VIC, Australia

Vikram Patel

14 Department of Global Health and Social Medicine, Harvard Medical School, Boston MA, USA

15 Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston MA, USA

Ilaria Bonoldi

16 Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London UK

Massimiliano Aragona

17 Roman Circle of Psychopathology, Rome Italy

Ana Cabrera

18 Asociación Española de Apoyo en Psicosis, Madrid Spain

Joseba Rico

19 Young Person's Mental Health Advisory Group (YPMHAG), King's College London, London UK

Jummy Otaiku

Nicholas hunter.

20 NHS South London and Maudsley (SLaM) Recovery College, London UK

Melissa G. Tamelini

21 Institute of Psychiatry, Hospital das Clínicas de São Paulo, São Paulo Brazil

Luca F. Maschião

Mariana cardoso puchivailo.

22 Department of Psychology, FAE University Center, Curitiba Brazil

Valter L. Piedade

Péter kéri.

23 Global Alliance of Mental Illness Advocacy Networks‐Europe (GAMIAN‐Europe), Brussels Belgium

Charlene Sunkel

24 Global Mental Health Peer Network (GMHPN), South Africa

25 Department of Forensic and Neurodevelopment Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London UK

David Shiers

26 Psychosis Research Unit, Greater Manchester Mental Health Trust, Manchester UK

27 Division of Psychology and Mental Health, University of Manchester, Manchester UK

28 School of Medicine, Keele University, Staffordshire UK

Elizabeth Kuipers

Celso arango.

29 Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, IiSGM, CIBERSAM, Complutense University of Madrid, Madrid Spain

30 Department of Psychiatry, University of Campania “L. Vanvitelli”, Naples Italy

Psychosis is the most ineffable experience of mental disorder. We provide here the first co‐written bottom‐up review of the lived experience of psychosis, whereby experts by experience primarily selected the subjective themes, that were subsequently enriched by phenomenologically‐informed perspectives. First‐person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of psychosis as well as family members and carers, representing a global network of organizations. The material was complemented by semantic analyses and shared across all collaborators in a cloud‐based system. The early phases of psychosis (i.e., premorbid and prodromal stages) were found to be characterized by core existential themes including loss of common sense, perplexity and lack of immersion in the world with compromised vital contact with reality, heightened salience and a feeling that something important is about to happen, perturbation of the sense of self, and need to hide the tumultuous inner experiences. The first episode stage was found to be denoted by some transitory relief associated with the onset of delusions, intense self‐referentiality and permeated self‐world boundaries, tumultuous internal noise, and dissolution of the sense of self with social withdrawal. Core lived experiences of the later stages (i.e., relapsing and chronic) involved grieving personal losses, feeling split, and struggling to accept the constant inner chaos, the new self, the diagnosis and an uncertain future. The experience of receiving psychiatric treatments, such as inpatient and outpatient care, social interventions, psychological treatments and medications, included both positive and negative aspects, and was determined by the hope of achieving recovery, understood as an enduring journey of reconstructing the sense of personhood and re‐establishing the lost bonds with others towards meaningful goals. These findings can inform clinical practice, research and education. Psychosis is one of the most painful and upsetting existential experiences, so dizzyingly alien to our usual patterns of life and so unspeakably enigmatic and human.

Psychotic disorders have a lifetime prevalence of 1% 1 , with a young onset age (peak age at onset: 20.5 years) 2 . They are associated with an enormous disease burden 3 , with about 73% of healthy life lost per year 4 .

Psychosis is characterized by symptoms such as hallucinations (perceptions in the absence of stimuli) and delusions (erroneous judgments held with extraordinary conviction and unparalleled subjective certainty, despite obvious proof or evidence to the contrary). The nature of these symptoms makes psychosis the most ineffable experience of mental disorder, extremely difficult for affected persons to comprehend and communicate: “There are things that happen to me that I have never found words for, some lost now, some which I still search desperately to explain, as if time is running out and what I see and feel will be lost to the depths of chaos forever” 5 .

K. Jaspers often refers to the paradigm of “incomprehensibility” with respect to the primary symptoms of psychosis that cannot be “empathically” understood in terms of meaningful psychological connections, motivation, or prior experiences 6 . However, psychotic disorders – especially schizophrenia – have, more than any other mental condition, inspired repeated attempts at comprehension.

In the two‐hundred‐year history of psychosis, numerous med­ical treatises and accurate psychopathological descriptions of the essential psychotic phenomena have been published. However, this top‐down (i.e., from theory to lived experience) approach is somewhat limited by a narrow academic focus and language that may not allow the subjectivity of the lived experience to emerge fully.

Some evidence syntheses have summarized various aspects of the lived experience of psychosis 7 , 8 , 9 , 10 , 11 , 12 , 13 , but again they were written by academics. On the other hand, numerous reports describing the subjective experience of psychosis have been produced by affected individuals 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 (see Table  1 ). Although useful, these reports are often limited by fragmented, contingent and contextual narratives that do not fully advance the broader comprehensibility of the experience.

Selection of publications on the lived experience of psychosis considered for the present review

To our best knowledge, there are no recent studies that have successfully adopted a bottom‐up approach (i.e., from lived experience to theory), whereby individuals with the lived experience of psychosis (i.e., experts by experience) primarily select the subjective themes and then discuss them with academics to advance broader knowledge. Among the various forms of collaboration available in the literature, co‐writing represents an innovative approach that may foster new advances 27 , 28 . It can be defined as the practice in which academics and individuals with the lived experience of a disorder are mutually engaged in writing jointly a narrative related to the condition. Co‐writing is based on the sharing of perspectives and meanings about the individual's suffering. Collaborative writing must honour the challenge of maintaining each subject's diction and narrative style without capturing or formatting them in pre‐established narrative models 29 .

The present paper aims to fill the above‐mentioned gap in the literature by providing a bottom‐up co‐written review of the lived experience of psychosis.

In a first step, we established a collaborative team of individuals with the lived experience of psychosis and academics. This core writing group screened all first‐person accounts published in Schizophrenia Bulletin between 1990 and 2021 30 , and retrieved further personal narratives within and outside the medical field through text reading (e.g., autobiographical books, see Table  1 ) and qualitative research (e.g., narratives from clinical records or service users' magazines or newsletters). The material was included if consisting of primary accounts of the lived experience of psychosis across its clinical stages (premorbid, prodromal, first episode, relapsing, and chronic). Primary accounts of the experience of recovery or of treatments received for psychosis were also included.

We performed automated semantic analyses on Schizophrenia Bulletin first‐person accounts, extracting the list of experiential themes relating to the disorder across its clinical stages and their interconnections, loading them into Gephi software, and building up network maps.

In a second step, the core writing group selected the lived experiences of interest, tentatively clustered them into broader experiential themes, and identified illustrative quotations. The material was stored on a cloud‐based system (i.e., google drive) fully accessible to all members of the group.

In a third step, the initial selection of experiential themes and quotations was collegially shared and discussed in two collaborative workshops, which involved numerous individuals with the lived experience of psychosis as well as family members and carers, to ensure that the most prominent themes were being considered and to collect users' and carers' interpretation of these themes.

The workshops involved representatives from the Global ­Mental Health Peer Network ( https://www.gmhpn.org ); the Glo­bal Alliance of Mental Illness Advocacy Networks (GAMIAN) ‐ Europe ( https://www.gamian.eu ); the South London and Maud­sley NHS Foundation Trust ( https://www.slam.nhs.uk ); the Young Person's Mental Health Advisory Group ( https://www.kcl.ac.uk/research/ypmhag ) ; the Outreach And Support in South‐London (OASIS) ( https://www.meandmymind.nhs.uk ) Service Users Group; the South London and Maudsley NHS Recovery College ( https://www.slamrecoverycollege.co.uk ); the Black and Minority Ethnic Health Forum Croydon ( https://cbmeforum.org ); the UK Mental Health Foundation ( https://www.mentalhealth.org.uk ); the Faces and Voices of Recovery ( https://facesandvoicesofrecovery.org ); and the Asociación Española de Apoyo en Psicosis (AMAFE) ( https://www.amafe.org ).

In a final step, the selection of experiential themes was revised and enriched by adopting a phenomenologically‐informed perspective 31 , 32 , 33 . The revised material was then shared again across all collaborators in google drive and finalized iteratively. All individuals with lived experience and researchers who actively contributed to this work were invited to be co‐authors of the paper. Representatives from service user and family groups were reimbursed for their time according to the guidelines by the UK National Institute for Health Research ( https://www.invo.org.uk ).

In this paper, the words spoken or written by individuals with the lived experience of psychosis are reported verbatim in italics, integrated by co‐authors' comments and phenomenological insights.

THE LIVED EXPERIENCE OF PSYCHOSIS ACROSS ITS CLINICAL STAGES

This section addresses the subjective experience of psychosis across the clinical stages of this condition: premorbid, prodromal, first episode, relapsing, and chronic 34 , 35 , 36 , 37 .

The premorbid stage starts in the perinatal period and is often asymptomatic; it is generally associated with preserved functioning 38 , although delays in milestones may emerge 39 . Accumulation of further risk factors during infancy and young adulthood 40 may lead to the emergence of a clinical high‐risk state for psychosis; this stage is often termed “prodromal” in the retrospective accounts of individuals with the lived experience. The prodromal stage is characterized by attenuated psychotic symptoms that can last years, do not reach the diagnostic threshold for a psychotic disorder, but are typically associated with some degree of functional and cognitive impairment 41 , 42 , 43 , 44 , 45 . These manifestations can then progress to a subsequent stage of fully symptomatic mental disorder (first episode of psychosis) and then persist, especially if treated sub‐optimally, leading to a relapsing stage and, for a proportion of cases, a subsequent chronic stage 38 .

Premorbid stage

An early, inner experience of loneliness and isolation.

“When growing up I was quite a shy child… I was usually uncomfortable around kids of my own age” 46 . Figure  1 shows that the most frequent cluster of lived experiences in the premorbid stage of psychosis is represented by feelings of loneliness and isolation – variably referenced as being “introverted” 47 , “loner” 48 , 49 , 50 or “isolated” 51 – already reported during childhood: “I admitted I was a loner and was probably somewhat backwards socially. I had never had a boyfriend, rarely even dated, and my friendships with girls were limited and superficial” 48 .

Network map of lived experiences of psychosis during the premorbid stage. The nodes represent the experiential themes, and the edges represent the connections between them. The size of each node reflects the number of first‐person accounts addressing that experiential theme. The thickness of the edges reflects the number of connections between the themes.

This weak “attunement” in social interactions during childhood 52 has been captured by Bleuler's 53 concept of “latent schiz­ophrenia” and Kretschmer's 54 definition of “schizothymic” and “schizoid” temperaments. Recent meta‐analyses have confirmed that loneliness is a core experiential domain during subclinical psychosis 55 . Loneliness has been frequently associated with experiences of social anxiety 46 , 56 and recurring fears 51 , 57 , 58 , 59 , 60 , ob­­sessive ruminations 59 , depressed mood 57 , and a heightened sensitivity to social interactions 14 , 60 , 61 : “I was too shy to raise my hand, and although my parents were very sociable and outgoing, I would hide behind my mum when meeting strang­ers” 23 .

These experiences color the emotional life of the individuals before the emergence of attenuated psychotic symptoms 51 , 58 . Loneliness is also frequently associated with early adverse experiences, such as social discrimination 60 , 62 , school bullying 50 , 60 , 63 , 64 , abuse or exposure to prolonged familial conflicts and violence 65 , 66 , which further amplify the sense of subjective alienation, fear and isolation (see Figure  1 ): “The abuse I had in my years of schooling… exacerbated anger and fear, which as I remember had always been there anyway” 60 .

Loss of common sense and natural self‐evidence

“ When I was younger, I used to stare at the words on the pages of a book until they became so unfamiliar that they were practically incomprehensible to me even if I had learnt their meanings before. Then I would wonder, why do words mean anything anyway? They are just letters put together by some unspoken rule… What is this hidden rule? The hidden rules that govern thoughts and behaviors were not transparent to me although others seemed to know them” 67 . Another core experiential theme during the premorbid stage of psychosis is this diminished intuitive grasp of how to naturally conduct natural, everyday tasks like reading a book or interactions: “I was forever making remarks and behaving in a way that would slightly alienate people. This was because I would have to grasp situations by apprehending their parts rather than grasping them intuitively and holistically” 60 .

Common sense is defined by Blankenburg 68 as the tacit (implicit) understanding of the set of “rules of the game” that disciplines and guides human interactions. A “crisis in common sense” 68 is the main root of the premorbid subjective experience of psychosis since childhood, intensifying over the subsequent stages 69 : “Rules about how to deal with others were learnt and memorized instead of being intrinsically felt. What should come naturally, and without effort, became a difficult cognitive task” 67 .

Fragile common sense erodes interpersonal attunement (and vice versa) and may drive individuals towards an eccentric self‐positioning that is marginal to commonsensical reality, situating them at the edges of socially shared beliefs 70 and values 69 , 71 . Fragile common sense relates to the subjective feelings of being “odd” 60 , 72 or “weird” 56 (see Figure  1 ). Individuals may feel ephemeral, lacking a core identity, profoundly (often ineffably) different from others and alienated from the social world, a state that has been termed “diminished sense of basic‐self” 73 , 74 : “ I remember it very precisely. I must have been 4 or 5 years old. I was starting dance class, and I was looking in the mirror. I was standing next to the other kids, and I remember that I looked alien. I felt like I sort of stuck out from that large wall mirror. As if I wasn't a real child. This feeling has been very persistent from very early on ” 75 .

Empirical studies have confirmed that this odd “feeling like a stranger” 62 (see Figure  1 ) and isolated (e.g., schizoid or schizotypal) personality organization may present features qualitatively similar to psychosis 76 , and be associated with an increased risk of later developing the disorder 52 . Detachment from common sense is also related to a pervasive sense of “perplexity” (see Figure  1 ), frequently characterizing the premorbid stage of psychosis 51 , 67 : “A certain perplexity has always been a part of how I experience the world and its inhabitants” 67 .

Abnormal body experiences, such as the sense of being a disembodied self , may also be reported: “ The first disturbing experience I remember was discomfort in my very own body. Because I didn't feel it. I didn't feel alive. It didn't feel mine. I was just a kid, but ever since, I never felt a feeling of fusion or harmony between ‘me ’ and ‘my’ body: it always felt like a vehicle, something I had to drive like a car ” ( personal communication during the workshops ).

Overall, the disconnectedness from common sense translates into real‐world feelings of inadequate social skills 48 , 56 , 60 , 66 , difficulties at school 57 , and problems in mundane daily activities 51 : “It made me inept about mundane things such as washing up, getting a haircut when I needed it, doing the bins, and little things like that – which really have to be done, just to get on with life” 51 . These impairments can be so profound as to disrupt the individual's identity 51 , 58 , 60 (Jaspers' awareness of the identity of the self, or ego‐identity 6 ).

Prodromal stage

A feeling that something important is about to happen.

The subjective experience of the psychosis prodrome is mark­ed by an intense feeling that something very important is “about to happen” 77 , that the individual is on the verge of finding out an important “truth” about the world 78 , 79 (see Figure  2 ). K. Conrad calls this initial expectation phase the Trema (stage fright) 77 . The Trema can last from a few days to months, or even years 6 , and is characterized by delusional mood ( Wahnstimmung in the German tradition): an “uncanny” (“ unheimlich ” in the German tradition), oppressive inner sense of tension, as if something ominous and impending is about to happen (“something seems in the air” 6 ), but the individual is unable to identify what this might be precisely 77 : “Something is going on; do tell me what on earth is going on” 6 .

Network map of lived experiences of psychosis during the prodromal stage. The nodes represent the experiential themes, and the edges represent the connections between them. The size of each node reflects the number of first‐person accounts addressing that experiential theme. The thickness of the edges reflects the number of connections between the themes.

During this experience, time is suspended. Individuals live in an elusive and pregnant “now”, in which what is most important is always about to happen. Premonitions about oneself ( “I felt something good was going happen to me” 60 ) and about the external world ( “Something is going on as if some drama unfolding” 60 ) are common.

Delusional mood, according to Jaspers, marks the irruption of a primary psychotic process (i.e., not due to other conditions) that interrupts the development of personality 81 . As the world transforms, the crisis of common sense of the Trema ­intensifies, and known places or people become strange 57 , 82 and lose their familiarity 83 , often acquiring a “brooding” 47 or threatening connotation 62 , 67 , 82 , 84 : “Suddenly the room became enormous, illuminated by a dreadful electric light that cast false shadows. Everything was exact, smooth, artificial, extremely tense; the chairs and tables seemed models placed here and there. Pupils and teachers were puppets revolving without cause, without objective. I recognized nothing, nobody. It was as though reality, attenuated, had slipped away from all these things and these people. Profound dread overwhelmed me… I heard people talking, but I did not grasp the meaning of the words” 22 .

Individuals feel as if they are the only ones noticing these changes: “I felt I was the only sane person in the world gone crazy” 62 . In contemporary terms, the uncanniness of the delusional mood has been described as “living in the Truman Show”, quoting a movie in which the protagonist, Truman, gradually starts to realize that he has been living his life in a reality television show, becoming increasingly suspicious of his surrounding world 85 , 86 : “All seemed ever more unreal to me, like a foreign country… Then it occurred to me that this was not my former environment anymore. Somebody could have set this up for me as a scenery. Or else someone could be projecting a television show for me… Then I felt the walls and checked if there was really a surface” 67 .

Heightened salience of meanings in the inner and outer world

During the prodromal phase of psychosis, individuals feel assaulted by events personally directed to them 67 , 79 , 82 , 88 , accompanied by a strong need to unravel their obscure meaning 67 , 79 : “A leaf fell and in its falling spoke: nothing was too small to act as a courier of meaning” 69 . Seemingly innocuous everyday events assume new salient meanings 78 , 83 , 89 . Previously irrelevant stimuli are brought to the front of the perceptual field and become highly salient 90 . This perceptual background, until then unnoticed, now takes on a character of its own 77 : “At first, this started with sudden new perspectives on problems I had been struggling with, later the world appeared in a new manner. Even the places and people most familiar to me did not look the same anymore” 83 .

The enhanced salience of the environment can become an overwhelming experience 79 , 89 : “It was shocking the amount of detail I found in this new world. In a day, there are so many things the mind relegates to background information” 79 . There­fore, individuals become increasingly preoccupied with new themes and interests – often involving religion 48 , 91 , the paranormal 59 , 91 , or sciences 49 , 92 – and ideas of reference emerge 46 , 47 , 51 , 62 , 72 , 82 , 84 , 92 , 93 , 94 , 95 (see Figure  2 ).

Perturbation of the sense of self

Another core experience is described as follows: “I thought I was dissolving into the world; my core self was perforated and unstable, accepting all the information permeating from the external world without filtering anything out” 67 . The normal lived experience of the world is intertwined with a stable sense of selfhood 96 ( “core self” 67 ), which demarcates the individuals from the surrounding world. During delusional mood with heightened salience of meanings and paranoid interpretation, the boundaries of the self are “ perforated ” 67 , the self becomes “permeated” 67 by the external world 51 and “unstable” 67 (see Figure  2 ).

A pre‐reflective sense of “mineness” (“ipseity” and Jaspers' awareness of being or existing 6 ) is the necessary structure for all experience to be subjective, i.e. to be someone's experience, instead of existing in a free‐floating state appropriated post‐hoc by the subject via an act of reflection 74 , 97 , 98 . This sense of ownership and agency (sense of “I”) of actions and emotions, that healthy people typically take for granted 99 , is essentially based on self‐presence and immersion in the world. The person's experience of being a vital subject of experience 97 is disrupted in psychosis, leading to experiences of dissolution 67 and losing one's sense of identity 51 , 66 : “ This vacuousness of self… one cannot find oneself or be oneself and so has no idea who one is ” 51 .

A key component of ipseity disturbances is hyper‐reflexiv­ity (exaggerated self‐consciousness and self‐alienation), in which inner mental processes such as thoughts become reified and spatialized, resulting in hallucinatory experiences 97 . During the prodromal phase, these abnormal perceptual experiences are reported as brief and remitting 100 , or intensifying over time 47 , 101 : “At first, hallucinations are often small or momentary and can be as small as the appearance of eyes or a whisper of a voice” 100 . Perceptual experiences include hearing indistinct chatter or distorted sounds 61 , 95 , 101 , voices 61 , 67 , 102 , or visions 78 , 82 , 88 .

The “mineness” of thinking and emotions is gradually compromised (diminished self‐affection 97 ): “Some thoughts didn't seem to be my own. They seemed foreign, as though someone was putting them there” 88 . Individuals complain about intrusive thoughts or impulses 103 , losing control over their emotional and cognitive processes 51 , 79 , 104 , 105 , or feeling under the influence of external forces 82 , although these experiences are typically transient.

Perplexity as lack of immersion in the world

An intense sense of perplexity is the hallmark of the emotional experience during the prodromal stage of psychosis 67 , 77 , 78 : “During that time reality became distant, and I began to wander around in a sort of haze, foreshadowing the delusional world that was to come later” 78 . Perplexity here refers to a lack of immersion in the world, an experience of puzzlement and alienation 106 which may acquire a threatening quality: “The sense of perplexity and feeling threatened by others preceded the fully formed voices by just over two years” 67 .

A pervasive sense of insecurity starts to creep in 82 , 84 , 89 , potentially leading to panic attacks 107 and experiences such as feeling empty, shut‐off, depressed 50 , 62 , 88 , 101 , 108 , angry or frustrated 57 , 105 . Substance use and social withdrawal are typical coping mechanisms (see Figure  2 ) 84 , 101 , 103 .

However, the prodromal phase of psychosis is not always tainted by anxiety 109 . Pleasurable emotional experiences can coexist 49 , 58 , 61 , 110 : “At that time I was working on an entirely new reality… with emotional gratification beyond any reasonable comprehension. In fact, I experienced it, but I also experienced terror and hell” 110 .

Compromised vital contact with reality

During the prodromal phase of psychosis, individuals tend to lose vital contact with the world, experiencing increasing difficulties in interacting and communicating with others 92 , 111 : “People were incomprehensible, as well as the world. I did not understand my peers why they could have so much ‘fun’ just by engaging in gossip or in a party. I much preferred my own company” 67 .

Individuals describe withdrawing from family and friends 62 , 95 from the early years gradually, over a long time 60 , 64 , 112 , and experiencing emotional distress, a sense of isolation 46 , 66 , and impairment of social skills 66 , 82 (see Figure  2 ). They feel out of place or unable to communicate with others 113 or grasp commonsensical implicit social codes 60 , 67 , or feel excluded 46 , 114 as if they were different or inferior 51 , 57 (see Figure  2 ): “I felt different and alone. Seeing so many people in the school halls made me wonder how my life could be significant. I wanted to blend in the classroom as though I were a desk. I never spoke” 57 .

These experiences have been variously linked to the concept of “autism” 115 in psychosis, which has been understood as a “withdrawal to inner life” (Bleuler 53 ), or as the “loss of vital contact with reality” (Minkowski 116 ) and, more recently, quantified by deficits in the related construct of social cognition 117 , 118 , 119 , 120 .

Keeping it secret

During the prodromal phase of psychosis, individuals typically keep their anomalous subjective experiences secret: “These things caused me considerable anguish, but I continued to act as normal as I could for fear that any bizarre behavior would cause me to lose my job” 62 .

Individuals often hide their experiences from family and friends over a very long time 82 , 111 because they feel ashamed 58 , 79 of negative consequences 82 , and fear being labeled as “crazy” or “insane” 51 , 78 , 108 or being laughed at 64 , hoping for their problems to “clear up” 121 : “ At 18, I couldn't study or focus but still kept everything to myself. My behavior looked ‘normal’ to others, as I was always a quiet child, an introvert” ( personal communication during the workshops ). Help‐seeking during the prodromal phase may be hindered by this difficulty of sharing the unusual experiences with others 122 . For children and young adolescents, it is generally harder to conceal their emerging symptoms 123 .

On the other hand, because of the insidious onset of the abnormal experiences, individuals may not realize that something “might be wrong” 67 , 82 . They may believe that it is common for other people to have these experiences 64 , 67 , or consider them “plausible” 49 .

Notably, not all individuals describe a prodromal phase, but some report an abrupt onset of the first episode 89 , 92 , 124 , 125 : “I experienced a great and normal life I was thoroughly enjoying, then I went straight into the first episode phase” ( personal communication during the workshops ).

First episode stage

A sense of relief and resolution associated with the onset of delusions.

The first psychotic episode is characterized by an intensification of abnormal experiences, as visually shown by the increased density of Figure  3 compared to Figures  1 and ​ and2 2 .

Network map of lived experiences of psychosis during the first episode stage. The nodes represent the experiential themes, and the edges represent the connections between them. The size of each node reflects the number of first‐person accounts addressing that experiential theme. The thickness of the edges reflects the number of connections between the themes.

A sense of resolution emerges as a core experiential theme (see Figure  3 ): “It really feels as if I am suddenly capable of putting things in perspective, that the light has suddenly switched on inside of my head and that because of this I am capable of reasoning again” 63 . The pervasive sense of uncanniness and perplexity of the Trema is replaced by Conrad's Apophany (revelation) 77 , an unexpected experience of clarity or insight 60 , 83 , 126 , 127 . The individual suddenly “ puts the pieces together ” 89 , 126 , 127 , be­coming aware of the “truth” in the world 79 or the “essence” of things 83 , discovering a delusional motif behind the abnormal perceptions and distressing experiences 79 , 83 (“ aha experience ” 77 ): “ All of a sudden there came this ‘intuition’: that they had chosen me for the experiment. I was chosen to incarnate myself in one body and come to earth. That explained why I felt a stranger in my body. And a stranger on the earth too” 128 .

Individuals report being unable to shift away from or transcend 77 these new delusional perspectives 83 , 113 , 129 , 130 , 131 : “I told myself that I suddenly saw the real truth of the world as it was and as I had never seen it before” 79 .

The onset of delusions can provide the individual with a newfound role in the world that is more thrilling and meaningful than the uncanny reality of the Trema 60 , 67 , 83 , 89 , 132 , 133 , alongside a sense of excitement 60 , 61 , 126 or relief 67 , 83 , 89 (see Figure  3 ): “A relationship with the world was reconstructed by me that was spectacularly meaningful and portentous even if it was horrific” 60 ; “ My destination after this is a place where everything is vibration, a pure state of consciousness, so elevated that everything is peace” 128 .

However, the sense of relief associated with Apophany is frequently contrasted with a difficult personal situation: “There was going to be a nuclear holocaust that would break up the continental plates, and the oceans would evaporate from the lava… My future wife and I were going to become aliens and have eternal life. My actual situation [however] was a sharp contrast. I was living in a downtown rooming house with only cockroaches for friends” 112 .

Delusions can be understood as new beliefs providing a satisfactory explanation of a strangely altered and uncanny reality and a basis for doing something about it – rather than incomprehensible and meaningless phenomena. Delusional beliefs can alleviate distress by replacing confusion with clarity, or promoting a shift from purposelessness to a sense of identity and personal responsibility 134 , 135 . Delusions can indeed enhance a person's experience of meaning and purpose in life 136 , contribute positively to establishing a “sense of coherence” 137 and partially provide a sense of purpose, belonging and self‐identity 138 .

Feeling that everything relates to oneself

The experience of delusion is often subjectively reported as: “Everything I ‘can’ grasp refers to ‘me’, even the tone of every voice I hear, or the people I see talking in the distance” 139 . In Conrad's model, Anastrophe (“turning back” of meanings) is the third phase following the “ aha experience ” 77 . All events and perceptions are experienced as revolving around the self (the “middle point”) 140 : “ I have the sense that everything turns around me ”, “ I am like a little god, time is controlled by me ”, “ I feel as if I were the ego‐center of society ”, “ I became in a way for God the only human being, or simply the human being around whom everything turns ” 141 .

The increased centrality of the self during a first psychotic episode (see Figure  3 ) is substantiated by the delusional self‐reference of messages on the radio or television 57 , 60 , 88 , the gestures or conversations of people in the street 57 , 100 , 139 , or even the color of people's clothes 130 : “Colors of jeans got more realistic” 142 . This is typically accompanied by a transformation of the experience of the lived space (i.e., the meaningful, practical space of everyday life). Individuals feel they are uncomfortably center‐stage. Other people look at them, spy on them, send them messages, or hide something from them. While in the center of the stage, individuals feel things directed to them bearing personal meanings: “Cat jumping cardboard box signified a spiritual change in me” or “TV, radio, people on buses refer to me” 142 . Individuals eventually become “overwhelmed” 79 , 89 , “flooded” or “swarmed” 139 by these external or internal stimuli, and the subjective experiences become exhausting 60 , 79 , 89 , 139 , 143 .

The self‐referential experiences are frequently associated with grandiose delusions 49 , 57 , 60 , 79 , 89 , 91 , 104 , 124 (“ To feel like I have everyone following me around, whether it's negative or positive, that alone is a force of power… knowing that you can influence people's mind in the right way ” 144 ), or with Truman‐like 49 , 72 delusions 85 , 145 ( “I deduced that I had been on a secret TV show all of my life, similar to the Truman Show” 49 ) (see Figure  3 ).

Losing agency and control of the boundaries between the inner subjective and the outer world

In the Anastrophe stage, the individual's sense of agency and control over the delusional belief is lost (see Figure  3 ): “As my delusional system expanded and elaborated, it was as if I was not ‘thinking the delusion’: the delusion was ‘thinking me’!” 60 ; “My paranoid delusions spun out of control. I was a slave to madness” 79 .

The experience of hallucinations dissolves the boundaries between the self and the surrounding world: “When I am psychotic, I feel as though my awareness is happening to me. It's a passive experience. I'm at the mercy of ‘my’ thoughts and ‘my’ perceptions of people” 139 . Individuals report single or multiple voices 100 , 104 , 146 , 147 , 148 , distorted sounds or whispers 149 or physicalized thinking 150 , visions 104 , 111 , tactile sensations of radiation 65 , electricity 151 or burning 149 on the skin (see Figure  3 ).

Some reported experiences seem to support phenomenologically‐informed models suggesting that hallucinations represent an organization of the inner dialogue 152 emerging from the ipseity disturbances described above 97 : “I avoid the use of ‘voice’ to describe what occurs in my thinking. Instead, I prefer to conceptualize these occurrences by saying it is as if I hear ‘voices’… It's difficult to really concretely define ‘voices’ for someone else. Sometimes it seems they serve as reminders of things I should or shouldn't do – doubts vocalized” 150 .

The sense of agency and ownership 153 and the boundaries of the self are particularly disrupted by commanding voices giving orders 104 , 139 , 146 , warnings 147 , insults 104 , soothing 104 , 150 (more rarely encouraging 66 ): “I felt trapped in a bewildering hole; felt like wreckage on a derailed and deranged alien train; felt like I was about to be destroyed” 64 . The emotional correlates of these experiences are ontological fear 78 , 89 and pervasive terror 84 , 126 , 139 (see Figure  3 ). The word “nightmare” 89 , 126 , 151 is often used to describe such intense anguish. A sense of entrapment is frequently reported 84 , 88 , 89 , along with feelings of guilt, embarrassment 66 , 103 , 151 and self‐blaming 111 , 154 (see Figure  3 ): “My shame at even hearing these words in my head ran deep, but I couldn't make them stop. I tried my best to suppress them, but they welled up like poison in a spring” 79 .

The experience of an increased permeability of ego boundaries or the blending of the internal and the external fields 78 , 155 , 156 , 157 is sometimes explicitly mentioned: “I lost my ego‐boundary which meant everything external and internal seemed like one blend ” 156 (“transitivism” for Bleuler 53 , “loss of ego‐demarcation” for Jaspers 6 ).

A dramatic dissolution of the sense of self and devitalization

The dissolution of the sense of self, already present during the prodromal phase (see Figure  2 ), becomes more intense: “I had the feeling that I was dissolving and that pieces of me were going out into space, and I feared that I would never be able to find them again” 78 . Individuals feel different from the usual self 65 , 101 , 114 ( “I felt distinctly different from my usual self” 114 ; “ I am only a response to other people; I have no identity of my own ” 158 ; “ I am only a cork floating on the ocean ” 158 ), split, divided or scattered into various pieces 57 , 63 , 78 (Jaspers’ loss of awareness of unity of the self, or ego‐consistency and coherence 6 ).

The disorder of the basic sense of self leads to a disruption of the feeling of “mineness” in relation to one's psychic or bodily activity (Jaspers’ awareness of activity of the self, or ego‐activity 6 ) and to experiences of deanimation or devitalization 159 (Scharfet­ter's 160 , 161 loss of awareness of being or existing, or ego‐vitality): “It was not me who was engaging in such behaviors. I was unaware of my actions, observing myself in the third person” 155 ; “ I walk like a machine; it seems to me that it is not me who is walking, talking, or writing with this pencil ” 122 ; “ A feeling of total emptiness frequently overwhelms me, as if I ceased to exist ” 162 .

The experience of dissolution of the self is more marked when the ego‐world boundaries are compromised by passivity phenomena involving feeling under the influence of external forces 114 , 155 ; thoughts being read, inserted or broadcast 88 , 114 , 163 (see Figure  3 ); body boundaries being violated by entities or forc­es ( “Someone cut open my head and inserted a bag”, “Areas of the body where forces enter” 164 ) or parts of the body being displaced (“ Mouth was where hair should be”, “Arms sticking out of chest” 164 ). Some individuals may even feel that their body or parts of it are projected beyond their ego boundaries into outer space (“ Arms disjointed from the body”, “Legs and arms dropped off” 164 ). Altered corporality experiences such as the disembodiment or distancing from one's own body or mental processes 157 often co‐occur, sometimes leading to somatic delusions 78 , 110 , 112 (see Figure  3 ): “ I thought my inner being to be a deeply poisonous substance” 78 .

These experiences are often associated with the sense of the world turning into an unfamiliar place 57 , 65 , at times chaotic and frightening 57 , which can resolve in apocalyptic beliefs about incoming wars 65 , 89 or the inevitable end of the world 88 , 110 , 112 , or nihilistic delusions 114 , 155 : “I had the distinct impression that I did not really exist, because I could not make contact with my kidnapped self” 114 .

The dissolution of the self can result in extreme self‐harm behaviors: “ When one's ego dissolves, it becomes a part of everything surrounding him; but at the same time, this unification entails the annihilation of the self – hence the suicidal ideation ” 155 .

Feeling overwhelmed by chaos or noise inside the head

The disorganization of thoughts is a prominent experiential theme 66 , 84 , 108 , 163 , 165 (see Figure  3 ): “My head is ‘swarming’ with thoughts or ‘flooding’. I become overwhelmed by all the thinking going on inside my head. It sometimes manifests itself as incredible noise” 139 . Words such as “rollercoaster” 124 , “whirlwind” 114 , “vertigo” 79 or “maelstrom” 5 are used by individuals to try to convey an experience of inner chaos and confusion, which is difficult to articulate accurately through language 151 (see Figure  3 ): “Being in a whirlwind is not a very good metaphor for that experience, but I have trouble finding words to describe it” 114 .

As one individual describes, thought disorder can be experienced as a “weakening of the synthetic faculty” . “My thoughts seemed to have lost the power to squeeze things to clear organization” 84 . The weakening of the natural “core self” that organizes the meaning and significance of events 166 can lead to a disturbed “grip” or “hold” on the conceptual field 97 .

Losing trust and withdrawing from the world

During the first episode of psychosis, individuals frequently report losing trust in others (see Figure  3 ): “While I was in hospital, I was frightened, but at the same time I felt safe. I knew the workers were there to help me, but I just couldn't trust anyone” 66 .

Persecutory delusions disrupt the atmosphere of trust that permeates individuals’ social interactions and familiar environments 167 : “For me, it was about losing trust to everyone” ( personal communication during the workshops ). The loss of trust extends to the individual's immediate social network, with suspiciousness towards neighbors, family members, friends or colleagues 78 , 92 , 95 , 107 : “I was afraid of people to the extent that I wouldn't come out of my room when people were around. I ate my meals when my family was either gone or asleep” 78 .

A sense of helplessness 101 , 155 can be associated with these experiences: “You feel very much alone. You find it easier to withdraw than cope with a reality that is incongruent with your fantasy world” 111 . Therefore, the first episode is lived as an intensely isolating and solipsistic experience 60 , 101 , 111 , 155 (see Figure  3 ): “Having no friends to visit and living alone in my apartment… I began to spend weekends sitting on the couch all day” 147 . Individuals frequently withdraw (Figure  3 ) from family and friends 66 , 147 , college or school 79 , 88 , adopting a reclusive lifestyle 104 .

Withdrawal from social life is often associated with the subjective inability to cope with the disrupted sense of self and the world 5 , 111 , the loss of pleasure and interest in social relationships 66 , delusion‐fueled fears 78 , 104 , increasing difficulties in understanding social interactions 79 , or communication difficulties 58 , 91 , 101 , 114 : “I thought that I must be in hell and that part of the meaning of this particular hell was that no one else around understood that it was hell” 78 .

Relapsing stage

Grieving a series of personal losses.

“At the time, my diagnosis was equal to the death sentence. Nothing could have been more devastating. Not even death itself” 62 . During the relapsing phase of psychosis, individuals are frequently confronted with a series of losses, leading to an experience of grief for their pre‐psychotic self 124 , 168 (ego‐identity 6 ) that impacts their confidence and self‐esteem 102 , 169 , 170 (see Figure  4 ): “It's hard to recall the past. Hard to accept things will be like this from now on” ( personal communication during the workshops ).

Network map of lived experiences of psychosis during the relapsing stage. The nodes represent the experiential themes, and the edges represent the connections between them. The size of each node reflects the number of first‐person accounts addressing that experiential theme. The thickness of the edges reflects the number of connections between the themes.

These losses frequently include their past identities, as individuals often feel that they have to assume the new role of “mental patient”: “I entered the hospital as Robert Bjorklund, an individual, but left the hospital three weeks later as a ‘schizophrenic’” 171 . Individuals also grieve their individuality 65 , 171 , as they feel different compared to others 133 : “At first, it made me think that I was weird and different from everyone else. I didn't like feeling that I wasn't a part of the main group of people in life who were healthy and/or “normal” 156 .

Public stigma 94 , 156 , 170 , 172 , 173 towards mental disorders fuels feeling of rejection 50 , 56 , 126 , 156 , 174 , further reducing social networks 50 , 66 , 101 , 130 , 169 , 174 , 175 and personal relationships 105 , 107 , 156 , 169 , 173 (see Figure  4 ): “People would constantly joke about mental illness, and it was difficult for me to deal with” 172 . As a result, individuals typically hide their diagnosis 92 , 94 , 102 , 156 , 173 , 174 , 176 : “I struggled with accepting the diagnosis, and I never told anyone about it” 156 .

Another personal grief is for the premorbid sense of autonomy, as even the most mundane activities can now represent enormous challenges 89 , 94 , 102 (see Figure  4 ): “Something as basic as grocery shopping was both frightening and overwhelming for me. I remember my mom taking me along to do grocery shopping as a form of rehabilitation… Everything seemed so difficult” 94 . Difficulties in completing daily activities, performing at school or work 57 , 58 , 78 , 102 , 110 , 175 , 176 , 177 and maintaining employment 47 , 57 , 94 , 95 , 101 , 110 , 114 , 124 , 174 trigger sentiments of frustration and discouragement 47 , 57 , 59 , 101 , 102 , 169 , 177 (see Figure  4 ).

Individuals also mourn the loss of the sense of meaning or purpose that psychotic symptoms provided during the “ aha ” and Apophany phases 132 , 133 : “In my delusions, I had been a heroine on a mission; now that I was back on medication, I spent most of my days lying in bed, hating myself with a vengeance. Grief? Who knows?” 133 . Commonly, individuals struggle with post‐psychotic depressive mood following the remission of acute symptoms 101 , 108 , 112 , 132 , feeling “flawed” 94 by a lack of accomplishments 169 , leading to feelings of hopelessness and fragility 178 or the belief of being a “failure” 94 (see Figure  4 ).

Feeling split between different realities

Following remission of florid symptoms, individuals can feel “split” between the outer world and the private delusional worlds 78 , 155 , 176 (see Figure  4 ): “A constant during most of these years under psychiatric care and in the three years leading up to them was the existence of an inner reality that was more real to me than the world's outer reality” 78 ; “The difference between normal reality and psychosis feels extraordinarily subtle. It can, in its subtlety, encroach on me without my even noticing… That's why, today, I have a healthy respect for the cunningness of psychosis” 139 . Individuals can also feel split about the diagnosis and the need for ongoing medication: “I find it difficult to accept the continued professional opinion that I should take medication for my ‘condition’ over the long term” 107 .

This phenomenon of “double awareness” 179 , in which the person continues to simultaneously live in two realities 98 (i.e., the real and the delusional world), was originally referred to by Bleuler 53 as “double‐entry bookkeeping”.

An uncertain future

Following remission of acute psychosis, individuals face the task of rebuilding their identities and goals 124 , 154 , 169 : “Eventually, as discharge from my two years of treatment drew close, I was asked the big questions. What did I want to do now?” 154 . In this context, a psychotic relapse can be interpreted as a threat or even the complete abolition of a person's goals and future. Individuals can feel that past aspirations and plans in life are now completely out of reach 94 , 127 , 177 : “In my eyes, my life was over. Everything I had dreamt of doing, and all my aspirations in life, were now nonexistent. I felt completely nullified” 66 .

The sense of uncertainty is enhanced by the lack of a clear roadmap ahead: “That's what getting out of schizophrenia is like: there are no clues, no map, no road signs like ‘wrong way’, ‘turn here’, ‘detour’, ‘straight on’. And it's dark, lonely, and very frightening. You want nothing to do with it, but your return to sanity is at stake” 139 . The unpredictable evolution of the disorder also contributes: “However, now what I want more than anything else is to be sure that the things that I went through will never happen again. Unfortunately, that is not an easy thing to guarantee” 46 .

The acceptance of the diagnosis and the related uncertain future typically begins during this stage, but often requires several years of inner struggles 66 , 88 , 92 , 139 , 156 .

Chronic stage

Coming to terms with and accepting the new self‐world.

During the chronic stage of psychosis, individuals often report feeling more optimistic about the future or believing that the worst is now behind them 47 , 57 , 58 , 59 , 61 , 62 , 78 , 91 , 94 , 95 , 101 , 124 , 129 , 150 , 170 , 177 (see Figure  5 ): “After more than 40 years of psychosis, I can now say, I feel better than I have ever felt in my life” 95 . Individuals may also report feeling more satisfied with their occupational activities than before 47 , 49 , 50 , 59 , 62 , 78 , 82 , 91 , 101 , 112 , 129 , 133 , 173 , 177 , 180 , 181 (see Figure  5 ).

Network map of lived experiences of psychosis during the chronic stage. The nodes represent the experiential themes, and the edges represent the connections between them. The size of each node reflects the number of first‐person accounts addressing that experiential theme. The thickness of the edges reflects the number of connections between the themes.

As the intensity of psychotic symptoms and the associated distress frequently decrease 127 , 147 , they can be more easily dismissed (see Figure  5 ): “I go out among people almost every day and, although I still feel ‘stared at’ and occasionally talked about, I do not believe, even if I am psychic, that I am an agent of God” 91 .

During this stage, individuals have often also learned how to cope more effectively with their symptoms, for instance ignoring the voices and delusional ideas, partially regaining a sense of agency or control 50 , 112 , 127 , 150 (see Figure  5 ): “I think the quality of the thought‐voices evolved as my health evolved. I no longer hear suggestions to run into traffic; if I did, I would refuse. I'm able to judge the appropriateness of the advice” 150 .

All this aids the individuals to come to terms with the diagnosis and its impact: “At 42, I think I'm slowly getting better or at least getting better at dealing with the difficulties that remain. I feel stronger and more stable now than ever before” 58 . Acceptance of psychosis and the new self 60 , 150 , 169 , 170 , 180 , 182 , 183 is a slow process that typically takes several years: “For a long time I searched for a lesson from my experience. What I learned was to build a new life and new dreams based on what I find myself capable of doing today” 89 .

However, a sense of grief and loss for the old self and the life before the disorder can still persist 124 , 133 , 150 , 168 , 175 , 184 : “Though I am working again, I have a pervading sense of loss about my life. This illness has affected all aspects of how I perceive myself and how others perceive me” 184 . This is accentuated when the individuals with lived experience of psychosis compare themselves with healthy peers 108 , feeling worthlessness or inferior 124 , 133 , 185 , 186 (see Figure  5 ).

Persisting inner chaos not visible from the outside

An unstable sense of self and the world can persist in this stage: “The clinical symptoms come and go, but this nothingness of the self is permanently there” 157 . These experiences can include an ongoing sense of unreality of the world 58 , 155 and disorientation 139 , 157 , and disorders of the sense of the self, such as devitalization, disintegration or disconnectedness 155 , 157 , 185 , loss of agency 149 , 187 , and fear of doing something that might have negative consequences 103 , 139 (see Figure  5 ).

A tumultuous inner world may be described, even if it is not “visible” from the outside 5 , with a constant feeling on edge from slipping away from reality: “Although on the outside things seem to have calmed down greatly, on the inside there is a storm raging, a storm that frightens me when I feel that I am alone in it” 5 . The experience may be aggravated by the feeling of not being able to trust one's own mind 5 , 185 , 188 (see Figure  5 ).

Loneliness and a desperate need to belong

While some improvements in socialization may be reported 47 , 49 , 50 , 82 , 101 , 114 , 127 , 133 , 175 , 180 , 181 (see Figure  5 ), social relationships tend to remain a major concern during the chronic stage of psychosis 63 , 112 : “I look at people, and I don't feel like one of them. People are strangers” 185 .

Pervasive feelings of loneliness and isolation 63 , 112 , 133 , 168 , 181 , 183 , 185 , 186 , 188 , including feeling “cut off from humanity” 185 , are commonly reported, and have been confirmed at meta‐analytical level 189 . There is often a strong and desperate call to feel understood, connected and accepted 5 , 133 , 185 (see Figure  5 ): “I need people to accept me enough to want to build a relationship with me… I feel cut off, cut off from humanity… I am already separated… I isolate myself on purpose because when I'm around others, that chasm between me and the world gets more pronounced; at least when I am alone, I can pretend I'm normal” 185 .

This desire for human warmth and closeness can be frustrated by equally intense fears of reaching out to people 5 , difficulties in communicating with others 185 , and not being able to convey the nature of psychotic experiences 5 , 58 (see Figure  5 ): “The more I try to speak, the less you understand me. This is why we stop trying to communicate… Not being able to communicate my basic feelings, not identifying with another human being, and feeling completely alone in my experience are killing me” 185 . Stigma and misunderstandings about mental disorders 58 , 110 , 133 , 139 , 168 , 173 , 180 , 184 , 186 , 188 , 190 and feelings of shame 185 amplify the experience of loneliness 49 , 173 (see Figure  5 ).

Difficulties in establishing and keeping social relationships 108 , 112 reiterate a weak attunement to the shared world of “unwritten” codes of social interactions (see Figure  5 ) 187 : “Making friends is pretty much a mystery to me. Even though I have made some friends in my life, I cannot seem to master or understand the skill” 188 . Individuals express this hypo‐attunement to the social world with statements such as: “I cannot associate with other persons”, “I always felt different, as if I belonged to another race” , or “I lack the backbone of the rules of social life” 191 .

THE LIVED EXPERIENCE OF RECOVERY AND OF RECEIVING TREATMENTS FOR PSYCHOSIS

This section explores the lived experience of recovery and of receiving treatments for psychosis. As the latter is determined by the type of care delivery platform and contexts, we first address the subjective experiences of receiving treatments across different mental health settings and subsequently focus on specific treatments. To reflect the multitude of possible experiences, we emphasize both core positive and negative aspects.

Recovery as a journey towards meaningful goals

Individuals feel that recovery extends beyond symptomatic improvement 192 ( “It is not necessarily the disappearance of symp­toms” 101 ), but rather is about achieving a sense of subjective control and being able to “do something about it” 193 : “Recovery to me means that, even if the delusions are not completely gone, I am able to function as if they are” 72 . Notably, “The road of recovery is totally different for each person and different in each stage and across different ages” ( personal communication during the workshops ).

Recovery from psychosis is commonly experienced as a cyclical and ongoing process that requires active involvement 94 , and is hardly ever “complete” 194 . This recovery “journey” 133 , 192 is filled with back‐and‐forth, rather than being a linear path with a set endpoint: “ a long, solitary journey, with almost as much shock and fear at its outset as with the psychosi s” 133 . It is, therefore, a dialectical process on its own. Or, as described in another account: “Recovery can be a process as well as an end… Recovery means finding hope and the belief that one may have a better future. It is achieving social reintegration. It is finding a purpose in life and work that is meaningful. Recovery is having a clear direction” 101 .

In more practical terms, recovery appears as a deep and protracted struggle to restore meaning and one's sense of self and agency 193 , 195 , 196 , re‐establishing an active relationship with the world 83 , 183 : “As I recover, I am also faced with rebuilding my identity and my life. Making the decision to end my career profoundly affected my sense of identity and self‐worth, and I have been left since searching for meaning and for a means by which I can continue to help others” 183 . As such, recovery is often understood by individuals as the ability to move towards meaningful goals 94 , 183 , 197 : “ Recovery for me means serving a purpose; I think it is important for me because I felt ‘useless’ when I struggled through psychosis” (personal communication during the workshops) .

The recovery process also involves a strengthening of the person's ego‐identity by building a sense of continuity with the past and a projection towards the future. Following a first episode, some young people view recovery as going back to their old selves, to “the way I was” 195 . For others, the recovery process requires a personal transformation of their identity and goals 183 and the acceptance, not only of the disorder 193 , but also of one's limitations: “ For me, recovery has been about admitting something is wrong, about acknowledging my limitations. Recovery language focuses on what the person can do; I had to look at what I couldn't do before I could start to get better” 185 . A such, recovery is not necessarily about returning to the “past self” 192 , but implies assimilation of the experience into a new sense of self and a transformed understanding of the world and the person's role in it 83 .

Some young people feel that the recovery experience lead them to mature or make essential changes in their social relationships 195 , 196 , 198 . Psychosis can also provide new perspectives on life and relationships, including insights into one's life history 183 , increased empathy towards others 94 , 124 , 172 , or a rebalancing of life's priorities 56 , 101 , 169 : “I have more empathy for others and have a deeper understanding of what the human body is capable of. These components that make up my reality, to me, are the essence of life” 66 .

Supportive relationships are critical facilitators of the recovery journey: “The key to recovery for me was having really good supporting relationships that didn't break when everything else was breaking” (personal communication during the workshops) . A relationship is perceived as helpful when it transmits hope for the future 58 , 94 , 105 , 177 , 197 , 199 : “Most importantly, my care team believed in the certainty of my recovery in a period of life when I just wasn't able to” 126 . Supporting relationships also facilitate understanding of the unusual experiences 6 , 200 , 201 in the context of compassionate 139 , 202 and positive attitudes 150 , and realistic expectations 203 .

The lived experience of receiving treatments across different health care settings

Inpatient care: a traumatic experience or a respite.

“The attendants carried me into the dark corridor. A jumble of voices bounced off the walls – harsh bellows, still murmurs, and authoritative orders – but to me, the sounds blended together in a common senselessness” 48 . Admission to a hospital commonly occurs in the context of fear, chaos and confusion 48 , 66 , 84 , fuelled by delusional ideas 49 , 124 , 182 .

Negative experiences of being admitted to inpatient wards can trigger a sense of isolation 132 , hopelessness and uncertainty for the future 49 , 66 , 204 : “I wondered if I was ever going to recover; I wondered if I was ever going to be normal” 66 , and are often more pervasive for young people who are inappropriately admitted to adult mental health services 205 : “There were only a few younger ones in their twenties or thirties… I had heard someone use the term "chronic wards"… It didn't sound like a nice term” 48 .

The subjective experience of compulsory treatment or physical restraint during inpatient care is typically recalled as traumatic: “The first time was very traumatic… I refused medication, and I was held down and injected by six staff. What I feel strongly about is that no one gave me a choice… [this] added to the trauma that I'd already experienced in my home, being yanked out to an ambulance… It was a very nasty experience" 206 . The experience is associated with feeling powerless 108 and lacking privacy 207 , which can be re‐traumatizing for those with previous histories of abuse 206 .

A perceived “lack of compassion” 208 from the staff can lead to a sense of being “dehumanized” 209 : “‘Noncompliant’, passive dependent, passive‐aggressive… they all mean the same thing: you're not really you” 209 . Negative experiences of inpatient care can discourage future attempts to seek help 84 , 151 , 204 and hamper long‐term trust in the health care system: “I think if you don't come out and get a good experience right after that, then that's how you perceive the whole system” 208 .

However, in other cases, hospitalization can bring a much sought‐after sense of safety and relief, particularly during acute psychosis 66 , 78 , 114 : “The hospital was a safe haven” 210 . Hospitalization can also alleviate the personal exhaustion which follows the efforts to maintain a semblance of normalcy: “It was a relief to be in a place where it did not matter if you went off somewhere in the middle of a conversation. It was a relief not to have to fight all the time to maintain a semblance of sanity… It was a relief to be able to be honest” 78 .

The hospital can therefore provide a “respite” from the stress of life outside 205 , at times providing opportunities for recreation and the incorporation of healthy habits 66 , 108 , as well as time to reflect on the past and plan for the future: “It gave me a chance to think about what I really wanted to do with my life. I no longer wanted to continue working at a dull job where I was unhappy… There should be more to life” 57 .

Following discharge, the hospital can remain a safe haven to go back to during times of distress: “At those points in my life, the safety (albeit restrictive safety) offered by an institution was preferable to the responsibilities I felt I could not handle outside” 211 . As such, individuals can develop an ambivalent relationship with hospitalization, given the mixture of negative and positive experiences, especially when compulsory treatment was involved: “It would be a while before I realized hospital was there to help me in crisis rather than to further torture me as the voices had threatened” 84 .

Social relationships in the ward may have a solid positive im­pact on the subjective experience: “I found the staff usually kind, competent, and extremely tolerant of me and my fellow patients” 211 . Positive experiences are also linked to opportunities for in‐ward socialization that counter the sense of isolation 48 , 132 , 172 , 199 . For some individuals, the ward experience provides support networks that can persist after discharge: “Being in hospital is a painful experience, but it's also a personal journey, and for me, it was forming friendships on the ward that pulled me through (and continues to do so)” 172 .

Preventive and early intervention services: promoting and restoring hope

The subjective experience of individuals accessing specialized preventive (e.g., clinical high‐risk) or early intervention services for psychosis is markedly different compared to standard inpatient units. These services provide specialized and youth‐friendly care during a clinical high‐risk state or first episode of psychosis 34 , 212 , 213 . Their focus on recovery is greatly valued by young users 214 , 215 , 216 : “ They get me more active. They encourage me to be interested in things and think that I have a future. I thought my life was coming to an end and they kind of encouraged me to see that there is life after psychosis” 216 .

Individuals value the support with everyday practical challenges – such as social relationships, employment and housing – suited to their actual needs and concerns 215 , 216 , 217 , provided by these services. In addition, when services are located within a youth‐friendly setting outside the “mainstream” psychiatric institutions, they are perceived to reduce the feeling of shame and self‐stigma often attached to accessing mental health care 217 , providing a “ human touch” 214 and high quality of relationships with the care team that are key in the recovery process 208 , 215 , 216 , 217 , 218 .

In particular, individuals appreciate the opportunity to be involved as “partners” in the treatment decisions, as well as the experience of being treated “ as a human being” 214 , 217 , since staff “listen and ask your opinion” 214 , while at the same time being allowed to “describe what I was experiencing” with their own words, rather than over‐relying on diagnostic labels 208 .

In addition, availability of staff 214 , 216 and continuity in care 216 , 218 are emphasized as positive aspects: “I was seeing my key worker every week or two, which was very good” 218 . Continuity in care has been highlighted as a key trust‐enhancing factor 219 : “Opening‐up to the therapist requires trust; it takes time to build up that relationship” (personal communication during the work­shops) .

Young users also value how these services support them in developing a positive sense of self by sharing their experiences with others 216 , 217 , 218 : “I've met quite a few people with similar problems to me, and it's helped because we've discussed how we're different and tried to suggest ways that can sort of help each other or help ourselves” 216 . Preventive and early intervention teams also provide a sense of certainty and safety 215 , 216 : “This is what I've been looking for, somebody who actually knows what they're talking about” 220 .

For young individuals at clinical high‐risk of psychosis, specialized care provides an opportunity to disclose the distressing experiences often kept hidden from family, friends and professionals. Understanding can emerge through a process of shared exploration and creation of links 221 between symptoms and life experiences: “This ‘normalization’ of my difficulties was one of the most helpful elements of therapy, as it very quickly reduced my fear of being ‘mad’, which had been the most disturbing of my worries” 222 .

On the other hand, discontinuity of care due to high staff turnover, whenever present, is felt like an essential source of frustration also within these services, as “ it takes a whole load of time to build up trust in someone” 218 . Furthermore, following symptomatic and functional improvements, individuals can gradually lower their engagement with preventive or early intervention services, that are perceived as an unnecessary and undesired reminder that they are under mental health treatment 218 , 220 : “As I've got better, it's not nice having somebody come in all the time, because it constantly reminds you that you're suffering from an illness” 218 .

Outpatient care: opening the gates to the community

In the lived experience of persons with psychosis, practical and accessible outpatient services promote autonomy and control: “ You can come for the treatment, and the gates are open for you to come” 223 , as well as fostering the sense of feeling welcomed: “ It gives you an idea of home, it does not have that mystification that it is that closed, trapped thing and that you are hospitalized behind closed bars” 223 . As a result, the experiences of receiving outpatient community care can provide an opportunity for strengthening social bonds and networks.

Friendly and easily accessible outpatient multidisciplinary teams are perceived of utmost importance to achieve this: “I feel good, this is a family, if I'm not feeling good, they reach out for me. So here I found the people that really helped me. Every single one of them, from the cleaning mister to the service coordinator" 223 . These positive experiences are also crucial for promoting treatment adherence: "What gets me here is fraternity… They gave me so much fraternity that I end up saying to the doctor that out there, in my first life, second life, third life and present life I never had as much fraternity as I'm having here, I'm not drooling, it is the truth" 223 .

On the contrary, negative experiences of outpatient care result from fragmented services that expose users to repeated assessments and excessive waiting lists due to inter‐professional miscommunication 126 , 224 . Individuals often feel struggling with ever‐changing care teams and limited appointment times that are not enough for professionals to get to know them beyond the diagnostic label: “The various mental health professionals I saw at three separate psychiatric hospitals reinforced my narrowly defined diagnosis. Little effort was made to look beyond the many incongruences of my condition” 171 . In addition, the competing theories about psychosis can cause confusion, as individuals can feel as if “[clinicians] see what they want on your psychosis” (personal communication during the workshops) .

The impersonal nature of some services can lead to an amplification of the inner feeling of objectification characterizing the experience of psychosis: “If you enter the psychiatric business as a patient, then you have a high chance of being reduced to a disturbing object or to the disorder itself. Only that which is significant to the diagnostic examination is seen and heard. We are examined but not really seen; we are listened to but not really heard” 65 . As a result, excessively bureaucratic clinical settings foster stigma and isolation 209 .

Individuals may also feel rejected by the service due to lack of expertise among staff: “There are no guidelines to do that” 65 . Additionally, outpatient services can be perceived as insufficient in their treatment offers when there is a narrow focus on one‐size‐fits‐all approaches 214 .

The lived experience of receiving specific treatments for psychosis

Social interventions: finding one's own space in the world.

“ I finally felt independent again. I was beginning to manage my mental illness. I was responsible again for my own space in the world ” 225 . Social interventions are perceived as supporting individuals in rebuilding their disturbed sense of self by fostering autonomy and independence 96 . As previously discussed, one core component of psychosis is the disruption of the person's natural engagement with the world. Following a first episode, young individuals often view their recovery as being able to feel “normal” again 195 , which essentially means reintegrating into society 192 , re‐entering the workforce or going back to study in socially valuable roles 193 . Therefore, they feel that interventions supporting their study or work help them in regaining their sense of purpose 177 , 202 and confidence 226 : “I waged this war not because I am so brave but because I absolutely had to in order to keep my job” 170 .

Interventions supporting an independent housing are also key in the process of strengthening personal agency, fostering stability, autonomy and independence 224 , 227 : “ Here [in the new house] I met new friends who accepted me. My attention shifted to pleasure and was increased through meeting new friends and enjoying the courses on offer ” 202 .

Social interventions are also essential to reduce the experience of isolation and shame. This applies in particular to peer‐support groups 180 , which “normalize” the psychotic experiences 208 , 217 , allowing the affected individuals to feel “liberated” and hopeful: “They just told me that the fact was, there are other people like you, and you can get better from it” 217 . Peer‐support groups also help individuals to feel connected 228 and more accepted 184 : “[The peer‐support group] allows people to share their experiences, rediscover their emotions, and prepare for new journeys… where we can all support each other toward the goal of recovery and a better life” 228 .

Social interventions are also felt as helpful to overcome the passive role of affected individuals, stimulating a more proactive engagement in their care: “ I feel less like an outsider and more like someone with something to offer ” 229 . The positive experience of receiving these interventions is enhanced by the dialogic co‐responsibility of the partnership established across various social actors, involving the community and the family 230 .

The negative aspects of the experience of social interventions occur when the personal values of affected individuals are not prioritized, becoming purposeless 186 : “ Occupational therapy was supposed to engage me in what the professionals deemed meaningful activity. So I painted, I glued, and I sewed. I was occupied, but where was the meaning ?” 132 . These adverse experiences are widespread when individuals are asked or expected to conform and socially perform like everyone else: “I have to do things differently… It is unfair for others to expect us to finally finish that college degree and finally get that job… It makes us feel ashamed and hopeless and depressed” 185 .

Furthermore, people with chronic psychosis often point out that adequate community integration requires a delicate balance between socially‐promoting activities and having the space for solitary time 78 , 231 , 232 . This feeling has been confirmed by ethnographic studies, indicating that people with psychosis may develop a particular way of feeling integrated within society by keeping “at a distance” (i.e., neither too close nor too distant) 233 , 234 : “I need to be alone… If I were living in the countryside, nobody would care about my solitude, but in the city, no one is allowed to live like a hermit” 234 .

Psychological treatments: sharing and comprehending one's experiences

Psychological treatments are perceived as essential to provide the first channel to open oneself about difficult‐to‐communicate psychotic experiences 226 , 235 : “ I wanted to learn to talk about my psychotic experiences, to communicate about them, and to learn to see their meaning ” 65 .

For many individuals, recovery requires developing a complex and meaningful understanding of their distressing experiences, which re‐establishes a sense of continuity in their life narrative and overcomes the disturbances of the awareness of identity 65 , 183 , 193 , 196 , 236 , 237 , 238 , 239 : “Psychotic episodes don't happen out of nothing. There's always a reason for it. Unless the person is helped to make sense of that, they are not properly recovered” (personal communication during the workshops) .

Given the intense search for explanations during the Trema phase of psychosis onset 240 , finding meaning through a shared collaborative process allows the individuals to feel understood by others 237 , reducing their sense of isolation and loneliness: “So powerful is this desire that I often speak fervently of the wish to place my therapist inside my brain so that he can just know what is happening inside me” 5 . However, not all individuals will necessarily succeed in discovering new meanings for their disorder: “I've never been good at the ‘finding meaning’ thing” (personal communication during the workshops) .

The experience of receiving psychological treatments is valued when it flexibly allows individuals to experiment 241 different approaches and strategies: “ My initial strategy for change was to take a break from the high‐stress activities that have historically triggered symptoms and to instead focus on ‘anchoring activities’ that I find personally meaningful, intellectually challenging, and conducive to ‘connectedness’ with others ” 183 . Therefore, the experience of these treatments is highly personal, as reflected by the range of psychological coping strategies subjectively preferred, including improving mental health literacy and recognizing early warning signs 94 , 151 , 172 , 210 , self‐monitoring 151 , 197 , 242 , 243 , developing meaningful alternative activities 108 , setting a routine 63 , 108 , learning to interact with the voices 150 , 238 , reducing stress or “triggers” 46 , 180 , 183 , 244 , relaxation 151 , 202 or distraction 245 , 246 techniques, sharing and discussing the experience with others 82 , 150 , 172 , 242 , 245 , 246 , or employing reality‐testing and disconfirmation strategies 46 , 88 , 131 , 232 .

On the contrary, psychological treatments are felt unhelpful when they are “forced” upon the individual or deny his/her individuality 186 : “The person needs to identify what psychotherapy works best for them – what works for me does not necessarily work for someone else” (personal communication during the workshops) . Poor attentive listening is also perceived as impeding the affected individuals to speak in their voice and share their meanings appropriately 247 . Moreover, during psychological treatments, individuals feel that voices should be balanced, with no dominant voice, even if there are different views 248 .

Psychotherapeutic relationships are also seen as not valuable if both parts are not allowed to contribute and learn: “Clinicians need to give space to the patient and learn from the patient. There's a lot to learn from the patient” (personal communication during the workshops) . Judgmental, preaching or lecturing attitudes 235 can lead to individuals feeling invalidated, which increases the experience of lacking agency, and feelings of isolation and discrimination: “ When I have been preached or lectured in talk therapy, I felt my thoughts were far less valuable and contributed less to the conversation ” 235 .

An excessive emphasis on a rationalistic (reality‐testing) approach in the psychotherapy of delusions and hallucinations is often perceived to aggravate 146 the sense of self‐alienation, potentially through the intensification of hyper‐reflexivity 249 , 250 . Under these circumstances, the experience of receiving psychotherapy may amplify the ipseity disturbance, perplexity, lack of common sense and sensation of being different from others that have been described above 251 : “My recollections of any professionals challenging my hallucinations or delusions [during psychotherapy] are filled with feelings of hostility and resentment. After that, I would just tell them whatever they wanted to hear about my progress” 146 .

Similarly, a psychotherapeutic attitude that discredits the lived experience of psychosis as “meaningless” aggravates the sense of self‐alienation: “Untold damage can be caused by ignoring or trivializing [the experiences]. When regarded as just bizarre or symptomatic of the illness and not psychologically treated with appropriate validity, the intrinsic states of withdrawal are often exacerbated” 186 .

Medications: struggling with ambivalent feelings

The experience of receiving medication for psychosis, in particular antipsychotics, is often complex and ambivalent: “ The lesson is that psychiatric medications have two sides, on the one hand creating adverse effects and on the other hand alleviating and preventing psychiatric symptoms ” 203 .

Medication is frequently considered helpful in alleviating distressing symptoms 61 , 92 , 127 , 243 or creating the necessary conditions for add‐on psychosocial or psychological interventions 60 , 88 , 252 . Medications are often perceived to rescue the core self from the perturbation of the disorder: “The experience of medication was such that there has never been any feeling that it has turned me into someone I am not; on the contrary, I always have felt that haloperidol removed all the barriers that were preventing me from being who I am” 60 . Medication can provide a sense of being normal, even if it does not wholly restore premorbid functioning: “I consider myself to be normal when I am on medication… And I do function normally when I am medicated, except for my inability to make friends” 188 .

These positive experiences often clash with the distressing side effects, which can impact the person's daily life abilities: “After two weeks, the side effects of risperidone became intolerable. I slept at least 16 hours a night. I had a voracious appetite, akathisia and severe anhedonia” 104 . In particular, for young people during a first episode, side effects are often perceived as severely limiting their social functioning abilities 195 . This is a common reason for medication abandonment or rejection 104 , 130 , 147 .

The person can thus feel conflicted 186 , 203 , due to having to choose between two challenging scenarios: “It is hard realizing that I probably will have to continue taking medications for the rest of my life, but the misery without them is terrible” 147 . The decision becomes then “a question of personal values” 253 : “[The person] must decide what side effects and what degree of symptoms are intolerable” 253 . It is worth emphasizing that shared decision‐making enhances the sense of personal agency and autonomy 61 , 108 , 148 , 150 , 172 , 186 , 210 .

Another negative experience of receiving antipsychotics is the feeling that one has not really recovered 195 or that something is “wrong” with oneself: “During each psychotic episode, my family tried to get me medical help. Medications were prescribed, but I refused to take them. I didn't believe anything was wrong with me… Those pills were for crazy people!” 92 . The associated desire to feel “normal” 48 may be asserted: “ I refused to go to any more doctors or take any more meds. I wanted to live a normal married life; normal people don't have to take pills to think clearly and act appropriately ” 254 .

Antipsychotics may be also perceived as necessary but not sufficient to promote a complete recovery: “ I have found that, although psychiatric medication aids in the management of some of my symptoms, it only treats part of the problem ” 61 . As a result, the combination of medication with other treatments is often regarded as more acceptable 57 , 127 , 243 , 255 , with varying combinations across the different phases of the recovery process: “At the beginning stage, pharmacological treatment was more important for me; it allowed me to be stable and be able to go on with my life. As I started to improve, the psychosocial treatments were more important” (personal communication during the workshops) .

Indeed, while providing symptomatic alleviation, medication may not address the underlying basic‐self disturbances described above that fuel and sustain symptom formation: “Medications can and do help with many of the frightening and distressing symptoms of schizophrenia, but they do not resolve anything beyond the apparent manifestation itself. What lies behind the symptoms is a tormented self, a highly personal experience unchangeable and irreplaceable by any physical treatment” 157 .

This paper is based on the lived experience of individuals who have gone through the semi‐darkness and shadows of a psychotic crisis. We have followed and transcribed the words of these individuals, their emotions and forms of expression, their anguish and despair, their hopes and their silent cry for help. The paper, therefore, belongs to all the individuals with a lived experience of psychosis who have co‐written it with researchers.

This double perspective on psychosis represents an innovative methodological attempt in the existing literature. It is only by following different paths and languages that it is possible to look at psychosis with fresh eyes that can capture the vividness of the subjective experience of suffering. This is best achieved by allowing personal insights to re‐emerge into life and putting ideologies and traditional ways of thinking in brackets.

Such an approach also helps to minimize injustices, especially those related to exclusion and silencing of the affected persons' voices, distortion or misrepresentation of their emotions, meanings, values and understanding of oneself and the other, unfair distribution of power, and unwarranted distrust 256 – i.e., preventing these persons from speaking for themselves about their own views and purposes because of others claiming to know what those views and purposes are.

We attempted to prioritize the patients' first‐person perspective rather than confining ourselves to descriptions of psychosis from a third‐person perspective. Although this paper is dedicated to outlining some of the essential (paradigmatic) ways psychosis expresses itself, there is no assumption that the material presented is necessarily comprehensive or generalizable to all individuals affected. Although psychosis may have a formal framework common to all its clinical expressions, the contents and ways of being manifested in it are personal and idiosyncratic. It is, therefore, evident that is no such thing as a unique experience of psychosis that can be delineated. Instead, a plurality of experiences has been captured, reflecting the intrinsic heterogeneous nature of psychotic disorders. Bleuler himself coined the term “schizophrenias” to acknowledge heterogeneous syndromes characterized by multiple presentations and different possible trajectories 53 , 257 .

Within these limitations, the present paper has first decomposed the experience of psychosis across core clinical stages. We have found that the early phases (i.e., premorbid and prodromal stages) are characterized by core existential themes spanning from loss of common sense, perplexity and lack of immersion in the world with compromised vital contact with reality, heightened salience and feeling that something important is about to happen, perturbation of the sense of self, and need to hide the tumultuous inner experiences. The first episode stage is denoted by some transitory relief associated with the onset of delusions, intense self‐referentiality and permeated self‐world boundaries, tumultuous internal noise and dissolution of the sense of self with social withdrawal. Core lived experiences of the later stages (i.e., relapsing and chronic) involve grieving personal losses, feeling split and struggling to accept the constant inner chaos, the new self, the diagnosis and an uncertain future. While these experiences partially blur across the different stages, the life‐course of psychosis is marked by an inner experience of loneliness, stemming during the premorbid phase and persisting until the chronic stage.

Finally, we analyzed the positive and negative subjective ex­periential aspects of inpatient and outpatient care, social inter­ventions, psychological treatments and medications. The experience of receiving these treatments is determined by the hope of achieving recovery, understood as an enduring journey of reconstructing the sense of personhood and re‐establishing the lost bonds with others towards meaningful goals 258 . Good practices of care for persons with psychosis are first and foremost based on the understanding of what it is like to live with psychosis and receive psychiatric treatments.

Although it is not easy to listen to and understand the human and experiential reality of patients who are about to relive or re‐express their stories, it is not possible to “do” psychiatry and to provide treatments without starting from these inner realities – from these lacerated subjectivities that yearn to be heard and understood. The present paper is a reminder to clinicians not to be afraid to descend in the therapeutic relationship with their patients affected with psychosis to penetrate their subjective world.

By comprehensively improving the understanding of what it is like to live with psychosis, this paper may additionally benefit several other areas. We hope that it will be widely disseminated across clinical networks as well as patient and family organizations, to substantially improve the mental health literacy of individuals affected with the disorder, their families and carers. The paper may also hold an educational potential to train junior doctors in psychiatry, medical students and other health care professionals. Furthermore, health care providers may access this co‐developed source of core subjective experiences to refine the design and delivery of mental health services.

On a research level, this paper resurfaces the psychological and existential essence of psychosis, going against the current tide of a psychiatry “without psyche” 259 , which reifies scientific epistemology silencing the fundamental expression of the human experience of psychosis. This observation is empirically corroborated by the imbalance on top‐ranking scientific journals (with some exceptions) between neuroscientific articles and the field of phenomenology and first‐person accounts. It is not possible to grasp the real and dialectical dimension of psychosis without a deep‐rooted phenomenological approach that goes beyond the categories of natural sciences. The experiences described here may help to unmask the series of prejudices and misunderstandings with which natural sciences often reduce the complexity of psychosis, and to reflect on the limits of knowledge in psychiatry and on the meaning of research in this area.

Overall, this paper reminds us that psychosis is one of the most painful and upsetting existential experiences, so dizzyingly (apparently) alien to our usual patterns of life and so unspeakably enigmatic and human.

A systematic review of postpartum psychosis resulting in infanticide: missed opportunities in screening, diagnosis, and treatment

• Review Article
• Published: 02 September 2024

Cite this article

• Alexandria Y. Alford 1 ,
• Alisha D. Riggins 2 ,
• Joanne Chopak-Foss 2 ,
• Logan T. Cowan 1 ,
• Emmanuela C. Nwaonumah 1 ,
• Tobi F. Oloyede 2 ,
• Sarah T. Sejoro 1 &
• Wendy S. Kutten 1  

Impacting 1 in 1000 women, untreated postpartum psychosis is associated with a 4% infanticide rate. This systematic review aims to identify factors that are associated with infanticide resulting from psychosis in the puerperal period and pinpoint areas of missed opportunity for intervention.

A systematic literature review was conducted in accordance with PRISMA guidelines to identify and synthesize cases of maternal infanticide among perinatal females with evidence of postpartum psychosis. Four independent reviewers screened 231 articles identified in searches of three databases (PsycInfo, PubMed, and Web of Science) for studies conducted from 2013 to 2023.

Twelve studies were included in the final review. Findings indicate that those experiencing puerperal psychosis have increased incidence of infanticide suggesting missed opportunities for intervention and treatment. Common factors in mothers who committed infanticide as a result of delusions and/or hallucinations associated with PMADs were identified, including lack of standardized screening tools, preference for traditional and/or cultural healing practices, and access to care.

The current body of evidence supports developing and evaluating clinical interventions aimed at improving maternal mental health outcomes and infant outcomes in perinatal women experiencing puerperal psychosis.

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Study conceptualization and methodology were primarily designed by Alexandria Alford and Alisha Riggins, with input from Joanne Chopak-Foss and Logan Cowan. Alexandria Alford and Alisha Riggins performed the literature search. All authors contributed to the article screening process. Critical appraisal was completed by Alexandria Alford, Alisha Riggins, Emmanuela Nwaonumah, Tobi Oloyede, and Sarah Sejoro. All authors contributed to the article drafting process. Article revision was completed by Alexandria Alford, Alisha Riggins, Joanne Chopak-Foss, and Logan Cowan.

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Alford, A.Y., Riggins, A.D., Chopak-Foss, J. et al. A systematic review of postpartum psychosis resulting in infanticide: missed opportunities in screening, diagnosis, and treatment. Arch Womens Ment Health (2024). https://doi.org/10.1007/s00737-024-01508-3

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Impacts of pfas exposure on neurodevelopment: a comprehensive literature review.

1. Introduction

2. materials and methods, 2.1. data sourcing, 2.2. exposure assessment, 2.3. outcomes, 2.4. covariates, 2.5. data extraction, 3.1. the intelligence quotient (iq), 3.2. attention-deficit hyperactivity disorder (adhd), 3.3. autism spectrum disorder (asd), 4. discussion, 5. conclusions, author contributions, conflicts of interest.

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Currie, S.D.; Wang, J.-S.; Tang, L. Impacts of PFAS Exposure on Neurodevelopment: A Comprehensive Literature Review. Environments 2024 , 11 , 188. https://doi.org/10.3390/environments11090188

Currie SD, Wang J-S, Tang L. Impacts of PFAS Exposure on Neurodevelopment: A Comprehensive Literature Review. Environments . 2024; 11(9):188. https://doi.org/10.3390/environments11090188

Currie, Seth D., Jia-Sheng Wang, and Lili Tang. 2024. "Impacts of PFAS Exposure on Neurodevelopment: A Comprehensive Literature Review" Environments 11, no. 9: 188. https://doi.org/10.3390/environments11090188

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Borderline personality disorder and early psychosis: a narrative review

Affiliations.

• 1 Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, Università Di Bologna, Via Zamboni 33, 40106, Bologna, BO, Italy.
• 2 Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, Università Di Bologna, Via Zamboni 33, 40106, Bologna, BO, Italy. [email protected].
• PMID: 37919718
• PMCID: PMC10623785
• DOI: 10.1186/s12991-023-00475-w

Background: The purpose of the present review was to summarize the main literature contribution on the relationship between borderline personality disorder (BPD) and early psychosis. While retracing the historical path of the term "borderline", specific attention was paid to psychotic and psychotic-like symptoms in BPD. Its relationship with At Risk Mental State was evaluated, as well.

Methods: This search was conducted on PUBMED/MEDLINE and PsycInfo, looking for "Borderline personality disorder, First Episode Psychosis, Early Psychosis, Ultra-High Risk AND/OR Clinical High Risk" for psychosis.

Results: Eight pertinent papers were identified on this topic. Their main findings were then discussed. The term "borderline" has undergone different changes in meaning and use, despite always referring to states considered on the fence between neurosis and psychosis. However, considering the history of psychopathology and its relationship with diagnostic manuals, little attention has been given to its psychotic features. Being those symptoms highly burdensome, this neglect has often led to misdiagnosis and under-treatment.

Conclusions: Psychotic symptoms in BPD can be severe and distressing. Nonetheless they can be easily neglected, and when found they challenge clinicians in defining a differential diagnosis to distinguish between BPD and Psychosis Spectrum Disorders. Given specific needs and interventions for these different conditions, a dimensional, rather than categorical, approach should be considered, as well as specific care pathways and monitoring should be advised.

Keywords: Borderline personality disorder; Diagnosis; Early detection; Early intervention; Early psychosis; First episode psychosis; Psychopathology; Schizophrenia spectrum disorder.

© 2023. The Author(s).

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Conflict of interest statement

The authors declare no competing interests.

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Palatal groove associated with periodontal lesions: a systematic review illustrated by a decisional tree for management

• Yvan Gaudex 1 , 2 ,
• Vianney Gandillot 1 , 2 , 7 ,
• Isabelle Fontanille 3 ,
• Philippe Bouchard 1 , 2 ,
• Stephane Kerner 1 , 2 , 4 , 5 &
• Maria Clotilde Carra 1 , 2 , 6  

BMC Oral Health volume  24 , Article number:  1037 ( 2024 ) Cite this article

Metrics details

Palatal groove represents a relatively uncommon developmental root anomaly, usually found on the palatal aspect of maxillary incisors. While its origin is controversial, its presence predisposes to severe periodontal defects.

This study aimed to provide a systematic review of the literature focusing on the varied diagnostic techniques and treatment modalities for periodontal lesions arising from the presence of palatal groove. Based on the existing evidence and knowledge, the study also provides a comprehensive decisional tree, guiding clinicians in the challenging decision-making process face to a palatal groove.

The literature search was conducted on Medline and Cochrane databases by two independent reviewers, who also performed the screening and selection process, looking for English written articles reporting on diagnosis and management (all treatment approaches) of periodontal lesion(s) associated with a palatal groove. Based on this literature, a comprehensive decisional tree, including a standardized palatal groove evaluation and tailored treatment approaches, is proposed. Moreover, a clinical case is described to demonstrate the practical application of the developed decisional tree.

Over a total of 451 articles initially identified, 34 were selected, describing 40 patients with 40 periodontal lesions associated with palatal grooves. The case report illustrates a deep, large, circumferential intra-bony defect on the palatal side of the tooth #22 associated with a shallow, moderately long palatal groove in an 18-year-old male patient. Following reevaluation, a single flap surgery was deemed necessary, combined with a regenerative procedure. At 2 years post-treatment, the tooth #22 is healthy, in a functional and esthetic position. The decision-making process, based on local and systemic patient’s conditions, should allow an early and precise diagnosis to prevent further complications and undertake an adequate treatment.

Palatal grooves are relatively rare; however, they are frequently associated with severe periodontal defects. The identification, diagnosis, prompt, and tailored management of the associated lesion is essential to mitigate potential periodontal and endodontic complications related to the presence of palatal groove.

Systematic Review Registration

[ https://www.crd.york.ac.uk/prospero/ ], identifier [C CRD42022363194].

Peer Review reports

Introduction

Palatal groove (PG) is defined as an anatomic anomaly characterized by the presence of a developmental groove on a dental root that, when present, is usually found on the palatal aspect of maxillary incisors [ 1 ]. Over the years, several terms have been used to describe this anomaly, including palatal or palate-gingival groove [ 2 , 3 ], developmental radicular anomaly [ 4 ], distolingual groove [ 5 ], radicular lingual groove [ 6 , 7 ], palatoradicular groove [ 8 , 9 ], radicular groove [ 10 ], and cinguloradicular groove [ 11 ].

The origin of the PG is controversial, but it is assumed to be related to the infolding of the enamel organ or Hertwig epithelial root sheath during the tooth development [ 12 ]. Additional hypogenetic root formation [ 13 , 14 ] as well as an altered genetic mechanism [ 15 ] have also been suggested.

PG is relatively rare. Everett et al. [ 5 ] reported a prevalence of PG on 2.8% of lateral incisors whereas Withers et al. [ 16 ] observed a PG on 2.3% of maxillary incisors (4.4% of maxillary laterals and 0.28% of maxillary centrals). Kogon et al. [ 8 ] examined 3168 extracted maxillary central and lateral incisors and found PG on 4.6% of them (3.4% of maxillary centrals and 5.6% of maxillary lateral incisors), with over half of the PG extending more than 5 mm apical to the cementoenamel junction leading to a localized periodontal lesion. The most recent study by Mazzi-Chevez et al. [ 17 ] observed 150 maxillary central incisors, lateral incisors, and canines with a micro-CT and found that PG affected 2% of central incisors and 4% of lateral incisors. In 100% of cases, the PG originated in the enamel.

As the term implies, PG is formed around the cingulum of the tooth and continues apically down from the cementoenamel junction, terminating at various depths and length along the root [ 18 ]. In contrast to maxillary bicuspids, incisors generally display a U-shaped groove.

This anatomic anomaly is frequently associated with a breakdown of the periodontal attachment involving the groove; a self-sustaining localized periodontal pocket can develop [ 4 ], where the PG itself provides a site for bacterial accumulation. The subsequent progressive inflammation along the PG and its apical portion may lead to periodontal and endodontic pathologic conditions [ 19 ]. Furthermore, there may be communication between the pulp canal system and the periodontium through the pulp cavity and/or accessory canals, which may also lead to combined endodontic-periodontal lesions [ 20 ]. According to the 2017 classification of periodontal and peri-implant diseases and conditions [ 21 ], PG can be classified as a localized tooth-related factor that modifies or predisposes to plaque-induced gingival diseases/periodontitis [ 22 ], and can be associated with periodontal abscess in non-periodontitis patients.

The prognosis for teeth with PG extending apically is often poor [ 12 ], highlighting the critical need for prompt and accurate diagnosis to avert further periodontal and endodontic complications, ultimately preventing tooth extraction. This study is fundamentally motivated by the scarcity of consolidated guidelines for managing such complex dental conditions. Hence, the objective of this study was to conduct a systematic review of the existing literature, focusing on the diagnosis and management of periodontal lesions linked to PG. Based on this review, the goal was to develop a comprehensive decisional tree, thereby proposing a standardized treatment protocol to aid in the clinical decision-making. This study also includes a clinical case report to demonstrate the practical application of the developed decisional tree, reinforcing its clinical relevance and utility.

Material and methods

Development of the systematic review protocol.

A protocol covering all aspects of the systematic review methodology was developed before starting the review. The protocol included the definition of: a focused question; the literature search strategy; the study selection criteria; the outcome measures; the screening methods; the data extraction; and the data synthesis. The protocol was registered in PROSPERO (CRD42022363194).

Defining the focused question

The research question was formulated according to the PICOS (Population, Intervention, Comparison, Outcome, Study) strategy, which identify the search and selection criteria as follows:

P: Patients with periodontal lesion(s) associated with a PG

I: PG identification (diagnosis) and management. All treatment approaches (non-surgical, surgical, with or without the adjunctive use of potentially regenerative materials, i.e. barrier membranes, grafting materials, growth factors/proteins and combinations thereof) were considered.

C: alternative treatment approach or no comparison.

O: periodontal parameters, including clinical attachment level (CAL, measure in mm), probing pocket depth (PPD, measured in mm), recession (REC, measured in mm), plaque index (PI, any validated clinical score), bleeding on probing (BOP) or other inflammatory indexes, radiographic bone loss.

S: Any type of human studies including case reports, with a minimum of 6 weeks follow-up after treatment. Only studies published in English were considered. Studies written in languages other than English, review articles, cell and/or animal studies, letters, editorials, conference summaries, commentaries, and studies considering PG with only an endodontic involvement or that used self-report assessment of treatment outcomes were not considered.

So, the focused question was formulated as follows: what is the efficacy of treatments for periodontal lesions associated with PG?

Search strategy

The literature was searched for articles published up to June 2022 on MEDLINE and Cochrane databases. Multiple combinations of pertinent search terms were employed (Supplemental Table 1). The reference lists of the included studies were also evaluated in order to identify additional articles. To ensure its reproducibility, the PRISMA guidelines were followed [ 23 ], and the PRISMA flowchart was filled [ 24 ] (Fig.  1 ).

PRISMA flow diagram on the selection process of the studies included in the systematic review

Literature screening and data extraction

The titles and abstracts of the initially identified studies were screened by two independent reviewers (Y.G. and V.G.). Then, the pre-selected studies underwent a full text evaluation to assess the final inclusion or not. All records for which inclusion was obtained “uncertain” for on reviewer, disagreement was solved by discussion between authors. Whenever needed, the authors of the selected studies were contacted to provide missing data.

Study screening and selection was carried out by using the Rayyan online software [ 25 ], which assisted the reviewers in the different step of the literature review process. Duplicate references were removed automatically using Mendeley software. Data extraction was carried out on a dedicated excel spreadsheet. The risk of bias assessment was carried out by using the Joanna Briggs Institute (JBI) scale [ 26 , 27 ].

The literature search resulted in 451 potentially relevant publications (Fig.  1 ). After the first selection step, based upon the title and abstract, 88 articles were pre-selected. After full-text evaluation, 34 articles were included and analyzed. All of them were case series and case reports. A total of 40 patients were described, of which 23 women (57.5%). The characteristics of the selected studies are presented in Table  1 . Their quality assessment is reported in Table  2 .

Qualitative synthesis of the literature

Among those 40 clinical cases, 12 cases report failed to provide a clinical description of the PG. Four studies described the PG depth alone, 17 studies described the PG length alone, and 7 studies provided a combined description of depth and length of the PG. From a periodontal point of view, the periodontal lesion morphology was correctly described (depth and width) in only 4 cases, 2 of which also reported the number of bony walls. Among the 22 cases reporting a diagnosis, 17 (77.3%) described combined endo-periodontal lesions, whereas 5 were purely periodontal lesions.

Endodontic involvement was present in 29 cases: 22 cases presented with a pulp necrosis, and 7 cases with an endodontic treatment. Pulp vitality was present in 10 cases and 1 case failed to report the endodontic status.

The endodontic treatment consisted in either a temporary filling (calcium hydroxide) later replaced by a definitive filling (gutta percha), or directly with a definitive filling (gutta percha) when indicated. Among those 29 endodontically treated teeth, 9 underwent an apicoectomy (using mineral trioxyde aggregate) at the surgical phase.

PG sealing was performed in 16 cases using mainly glass-ionomer cement but also mineral trioxide aggregate (MTA), tricalcium silicate cement, composite flow and amalgam. In 5 cases, an extra-oral filling of the groove was performed before the tooth reimplantation. In all cases, radiculoplasty was performed either for groove removal when it was shallow or by saucerization to allow a proper filling when grooves were deep.

To treat the PG associated periodontal defect, several different intervention types were described, using: allogenic bone, xenogeneic bone, alloplastic materials, barriers, growth factors and biological factors (and combinations thereof). These surgical regenerative procedures were reported in 25 cases. Only 2 cases [ 3 , 40 ], justified the use of biomaterials and flap designs in relation to the analysis of the associated periodontal lesion after PG management.

All cases reported clinical healing except for 2 cases of failures following tooth reimplantation due to external root resorption leading to tooth removal after 36 months [ 33 ] and 2 failures after 6 months following a surgery without regeneration or root filling [ 29 ]. The case with the longest follow-up (324 months) indicated that following an endodontic treatment with a periodontal regeneration and an orthodontic treatment, a recurrent periodontal breakdown occurred 11 years, leading to tooth extraction and implant placement [ 35 ].

Case-report

We describe the case of an 18-year-old male patient referred to the periodontics department of the Rothschild Hospital (AP-HP) in Paris. Written informed consent was obtained for the publication of clinical data and images included in this article. The patient was experiencing pain due to the inflammation on the palatal side of tooth #22 with intermittent suppuration. The clinical examination revealed a central, shallow, and of moderate length (up to 70% of the root length) PG on the tooth #22, with a probing pocket depth of 12 mm on the palatal side associated with a tooth mobility 3 (Mühlemann 1951). The tooth responded positively to electrical test. At the radiographic evaluation, bone loss could be noted mesially and distally of #22 (Fig.  2 ).

Case report. Clinical and radiographical initial situation of the tooth #22 presenting with a palatal groove. The periodontal charting showed deep periodontal pockets on the palatal probing sites associated with bleeding and plaque accumulation

A slight bony bridge could be distinguished between #21 and #22 in the coronal portion. Thus, a localized periodontal defect due to the presence of subgingival PG was diagnosed.

The periodontal treatment first consisted in a non-surgical debridement performed in one session. Tooth splinting was performed from #21 to #23 to minimize mobility (Fig.  3 ).

Root planning and flattening of PG on tooth #22: initial occlusal view of #22 ( a ); Manual scaling 22 ( b ); flattening of PG 22 in the coronal part ( c )

At the re-evaluation 8 weeks later, the tooth presented no superficial inflammation, but a persistent periodontal pocket of 12 mm deep on the palatal side. Surgery was indicated due to the presence of a large, deep, 3-wall intra-bony defect around tooth #22 (Fig.  4 ).

Regenerative therapy: view at the periodontal re-evaluation, 2-months after the initial treatment ( a ); large and deep 3-walls intra-bony defect ( b ); application of EMD ( c ); application of DBBM (soft tissue support, osteoconductive) ( d ); sutures ( e ); radiographic image at the 2-month follow-up ( f )

A SFA (Single Flap Approach) was designed with a surgical access limited on the palatal side for esthetic reason and optimal visualization. A full periosteal flap was raised, and the granulation tissue was removed. The aberrant local anatomy was corrected up to the most apical part and a regenerative procedure combining enamel matrix derivates with a bone substitute was applied to avoid soft tissue shrinkage and collapse. Sutures with a non-resorbable monofilament 6/0 were made using U-crossed and single points. A postoperative radiograph was taken (Fig.  4 f). An antibiotic therapy with amoxicillin (1 g twice a day for 7 days) was administered. Paracetamol was prescribed as a painkiller and a mouthwash containing 0.12% chlorhexidine gluconate were prescribed for 2 weeks postoperatively. Healing was uneventful and sutures were removed 10 days postoperatively.

At the 6 months reevaluation, the periodontal pocket was no deeper than 4 mm on the palatal side with no bleeding on probing. A recession of 1 mm was observed. Radiographically, a mineralized tissue could be observed up to both bony peaks mesially and distally to #22 (Fig.  5 ).

Re-evaluation at 6 months ( a ); 18 months ( b ) and 30 months ( c )

At the 1-year follow-up, periodontal health was maintained and an orthodontic treatment was undertaken. After 2 years of treatment, tooth #22 is still healthy with a CAL gain of 7 mm, a functional and esthetic position resulting in the patient’s satisfaction. These results support that periodontal regeneration can be effectively carried out also for deep intra-bony defect associated with PG, once the local risk factor has been adequately managed.

The results of the present systematic review indicate that PG are relatively uncommon root anomaly, but they are frequently associated with periodontal lesion that require treatment. The selected studies showed that PG can be managed concomitantly with periodontal regeneration, with or without associated endodontic treatment. It must be noted that the presence of a PG may play a significant role in exacerbating periodontal lesions. This could be explained, at least partly, by the mediation role of inflammatory factors like the TGF-B1, which is involved in the regulation of the inflammatory response and in the remodeling of periodontal tissues, as highlighted by recent studies [ 58 , 59 ]. These findings necessitate a nuanced and well-defined diagnostic and therapeutic approach, which should consider not only on the anatomical challenges linked to the presence of a PG but also on the underlying inflammatory mechanisms, in order to ensure an effective treatment and prevent potential endodontic complications.

A variety of treatments approaches has been described in case reports and case series and summarized in the present review. The appreciation of the morphology and origin of PG on maxillary incisors may be challenging and thus delay the diagnosis and treatment planning. Therefore, developing a standardized approach based on the available literature is advisable.

A PG can be classified according to its location, length along the root, and depth of the groove towards the pulp cavity [ 60 ]. The analysis of the associated periodontal lesion is also a key parameter to consider. Based on the work of Kim et al. [ 60 ], a simplified version including the groove description and the periodontal parameters has been suggested. Such a classification (Table  3 ) would provide the clinician with precise criteria to justify the therapeutic approach.

Groove location was disregarded in most cases, only one case [ 40 ] reported a distal location of the PG. It can be explained by the fact that this parameter will not affect the prognosis or the treatment sequence. In the latest study done on extracted teeth, PG appeared to originate in the distal area of the cingulum margin in most cases (65%), followed by the central fossa (25%), and the mesial area of the cingulum margin (10%) [ 61 ].

In terms of depth, only 7 cases reported a shallow PG (50%) and 7 cases reported a deep PG (50%) and no closed tube has been described. This finding is in accordance with Kogon’s study [ 8 ] where 44% percent of the PG were described as shallow depressions, 42% as deep depressions, and 4% as closed tubes.

Considering the groove length, 4 cases reported an extension in the cervical third of the groove (17%), 6 in the middle third (25%) and 14 cases in the apical third (58%). According to Pinheiro’s study [ 61 ], those grooves extended rarely only to the cervical third (5%), followed by the middle thirds (45%) and the apical thirds of the root in most cases (50%). It is of paramount importance for clinicians to understand the combination of both variations of groove depth along with their length to adapt an adequate treatment considering the fact that PG with deeper grooves and greater degree of extension are the determinants and predictors of poor prognosis periodontally and endodontically wise [ 5 , 31 , 42 ].

Considering the groove description in the selected studies, most of them failed to adequately report it. Only 7 of the 40 cases described the depth and length of the PG. This lack of analysis might result in an inadequate treatment highlighting the need for a classification.

Considering the periodontal approach of the associated intra-bony defect, the selection of the regenerative biologic principle (or material) to use with the soft tissue surgical approach dependeds on the morphology of the intra- bony defect (width, depth, and number of residual bony walls) and on the amount (and quality) of the soft tissues available to cover it [ 62 ]. As a general rule, deep and wide defects with only one residual bony wall require a mechanical stabilizer of the blood coagulum (membrane and/or bone filler), whereas in defects with lower defect angles and a greater number of bony walls, biologic mediators of the healing process (e.g. enamel matrix derivates) are indicated [ 62 ]. In the present study, only 2 cases [ 3 , 40 ] succeeded in justifying the use of their regenerative procedure based on the description and analysis of the associated intra-bony lesion. As for PG anatomy, this lack of description of the associated periodontal lesion morphology could mislead the diagnosis and result in a non-optimal treatment. The PG issue had mostly been a concern for endodontist based on those case reports coming from endodontic journals, which might explain the few periodontal parameters reported and the lack of a clear description of the intra-bony defect associated to justify the different management of the periodontal defect. Moreover, the selected case reports do not cover all potentially applicable regenerative techniques, which continue to evolve [ 63 , 64 , 65 ] and should be further investigated in the particular context, from the microbiological and inflammatory perspectives, of PG-associate lesions.

Based on the presented literature review and in order to guide clinicians towards a comprehensive and complete evaluation of PG associated lesion, we suggested a decisional tree (Fig.  6 ) that introduces the periodontal parameter in the PG assessment, after evaluating the endodontic status. Indeed, the successful management of a tooth with a PG is firstly dependent on endodontic status, which should be systematically assessed. In cases of negative pulp response and periapical lesions, an endodontic treatment has to be undertaken in the first place [ 66 ]. But, the periodontal evaluation is also cardinal to obtain a successful and long-lasting management of PG.

Decisional tree. This graph proposes a decision-making process for the management of PG-associated lesions that takes into account the endodontic status, the characteristics of the palatal groove, and the presence of intra-bony defect

The recognition and management of PG for tooth survival has been reported in details in a study done by Kim et al. [ 60 ] in 2017. In the rest of the considered literature, half of the treatments described were made without a clear initial diagnosis or proper description of the associated lesions to justify the type of regenerative strategy and flap design approached. Another interesting observation made in this review is that in the case of intentional replantation, among the 5 reported cases, 2 resulted in a failure necessitating the tooth removal [ 33 ]. This suggests that replantation strategy should be used as a the latest resort for complex cases involving a PG to the apex with a deep groove.

It must be acknowledged that the available literature and thus the present systematic review present several limitations. Firstly, as mentioned above, there is a lack of standardization in the diagnostic and treatment processes, with a high heterogeneity among the selected articles, most of the times case reports or case series. Secondly, the follow-up time was mostly set between 6 and 24 months, which may be too short to assess treatment outcomes or observed complications and relapse. Indeed, after a 36 months follow-up, failures have been reported [ 33 ] and after 10 years, a periodontal breakdown occurred on a treated tooth [ 35 ] and both resulted in the tooth removal. No re-entry surgery and/or histologic evaluations were described and no prospective longitudinal studies evaluating the stability of the clinical and radiographic parameters and the absence of the recurrence of disease were found. Thus, any conclusion about the success achieved with the treatments described in the present review should be drawn with caution as the long-term prognosis of the treatment of PG-associated lesions of teeth remains to be determined. Updates of case series and case reports that could describe results after 5, 10 and 15 years from the initial PG diagnosis are advocated. Finally, the level of the body of evidence on PG is considered as low. Although the nature of PG as rare condition may explain why mainly case reports or case series are published, future clinical and comparative studies should be designed to investigate PG management and treatment success at long term. Nonetheless, based on the currently available literature, a decisional tree (Fig.  6 ) has been proposed to guide clinicians and create a reference for PG management to respond to a patient’s health condition. This should be periodontally updated as new evidence emerges but in the meantime, it can be useful to provide a clinical guidance as well as a model for the standardization of the diagnostic and treatment processes in clinical cases dealing with PG management.

Teeth with PG represent a challenge for clinicians. Despite their rarity (2% of maxillary lateral incisors), the complexities associated with PG, such as diverse anatomical features and clinical scenarios, underscore the necessity for accurate diagnosis and tailored treatment approaches. This study provides a systematic review of pertinent literature, consisting mainly in case reports, and culminates in the proposal of a decision tree, which aims to assist clinicians in the decision-making process through a structured evaluation of the PG characteristics guiding the treatment approach. The ultimate goal is to mitigate potential periodontal and endodontic complications of PG while providing a successful management. In parallel, the present study highlights the need of future research on this topic, particularly with clinical studies with a sufficiently long follow-up to monitor the treatment outcomes and their stability over time. Indeed, further evidence is needed to develop standardized diagnostic and treatment protocols for PG.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

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Service of Odontology, Rothschild Hospital (AP-HP), 5 Rue Santerre, Paris, 75012, France

Yvan Gaudex, Vianney Gandillot, Philippe Bouchard, Stephane Kerner & Maria Clotilde Carra

Department of Periodontology, UFR of Odontology, Université Paris Cité, 5 Rue Garanciere, Paris, 75006, France

Service of Odontology, CH Eure Seine Hospital, Evreux, France

Isabelle Fontanille

Cordeliers Research Centre, Laboratory of Molecular Oral Physiopathology, Paris, France

Stephane Kerner

Department of Periodontology, Loma Linda University School of Dentistry, Loma Linda, CA, USA

INSERM- Sorbonne Paris Cité Epidemiology and Statistics Research Centre, Paris, France

Maria Clotilde Carra

Institution Nationale Des Invalides, Paris, France

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Y.G. and V.G. drafted the manuscript text, and were involved in the literature review, data acquisition, analysis, and interpretation. Y.G. and V.G. prepared Tables 1 and 2 . Y.G., P.B. and I.F. Contributed the case report and Figs.  2 , 3 , 4 and 5 M.C.C and S.K. prepared Table  3 and Fig.  6 . M.C.C., P.B. and S.K revised the draft of the manuscript and contributed to the general criticism. All authors reviewed and approved the manuscript.

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Gaudex, Y., Gandillot, V., Fontanille, I. et al. Palatal groove associated with periodontal lesions: a systematic review illustrated by a decisional tree for management. BMC Oral Health 24 , 1037 (2024). https://doi.org/10.1186/s12903-024-04771-z

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DOI : https://doi.org/10.1186/s12903-024-04771-z

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