The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Psychosocial functioning in the balance between autism and psychosis: evidence from three populations.

Functional impairment is a core feature of both autism and schizophrenia spectrum disorders. While diagnostically independent, they can co-occur in the same individual at both the trait and diagnostic levels. The effect of such co-occurrence is hypothesized to worsen functional impairment. The diametric model, however, suggests that the disorders are etiologically and phenotypically diametrical, representing the extreme of a unidimensional continuum of cognition and behavior. A central prediction of this model is that functional impairment would be attenuated in individuals with mixed symptom expressions or genetic liability to both disorders. We tested this hypothesis in two clinical populations and one healthy population. In individuals with chronic schizophrenia and in individuals with first episode psychosis we evaluated the combined effect of autistic traits and positive psychotic symptoms on psychosocial functioning. In healthy carriers of alleles of copy number variants (CNVs) that confer risk for both autism and schizophrenia, we also evaluated whether variation in psychosocial functioning depended on the combined risk conferred by each CNV. Relative to individuals with biased symptom/CNV risk profiles, results show that functional impairments are attenuated in individuals with relatively equal levels of positive symptoms and autistic traits-and specifically stereotypic behaviors-, and in carriers of CNVs with relatively equal risks for either disorder. However, the pattern of effects along the "balance axis" varied across the groups, with this attenuation being generally less pronounced in individuals with high-high symptom/risk profile in the schizophrenia and CNV groups, and relatively similar for low-low and high-high individuals in the first episode psychosis group. Lower levels of functional impairments in individuals with "balanced" symptom profile or genetic risks would suggest compensation across mechanisms associated with autism and schizophrenia. CNVs that confer equal risks for both disorders may provide an entry point for investigations into such compensatory mechanisms. The co-assessment of autism and schizophrenia may contribute to personalized prognosis and stratification strategies.

Relationship between perceived coercion and perceived justification of coercive measures - secondary analysis of a randomized-controlled trial.

BACKGROUND: Subjective perception of coercion has gained attention as an important outcome. However, little is known about its relation to patients' appraisal of the justification of coercive measures. The present study aims to analyze the relationship between patients' appraisal of the justification of coercive measures and their level of perceived coercion. METHODS: This study presents a secondary analysis of the results of a multi-center RCT conducted to evaluate the effects of post-coercion review. Patients who experienced at least one coercive measure during their hospital stay were included in the trial. Participants' appraisal of the justification of coercive measures was categorized into patient-related and staff-related justifications. Subjective coercion was assessed using the Coercion Experience Scale (CES) and used as dependent variable in a multivariate regression model. RESULTS: 97 participants who completed the CES were included in the analysis. CES scores were significantly associated with the perception of the coercive measure as justified by staff-related factors (B = 0,540, p < 0,001), as well as with higher level of negative symptoms (B = 0,265, p = 0,011), and with mechanical restraint compared to seclusion (B=-0,343, p = 0,017). CONCLUSIONS: Patients' perceptions of coercive measures as justified by staff-related factors such as arbitrariness or incompetence of staff are related to higher levels of perceived coercion. Multiprofessional efforts must be made to restrict the use of coercive measures and to ensure a transparent and sustainable decision-making process, particularly with patients showing high levels of negative symptoms. Such key elements should be part of all coercion reduction programs.

Exploring the Latent Structure and Convergent and Incremental Validity of the Metacognition Assessment Scale - Abbreviated in a Sample of Patients with Non-Affective Psychosis.

Synthetic metacognition is a heterogeneous construct related to psychotic disorders. One important tool to assess this construct is the Metacognition Assessment Scale - Abbreviated (MAS-A). In this study, we investigated the latent structure as well as the interrater reliability and convergent and incremental validity of the MAS-A in a sample of patients with non-affective psychosis. Analyses indicated that the scale might be one-dimensional. Interrater reliability of the MAS-A total score was good. In terms of convergent validity, correlational analyses showed significant associations of MAS-A metacognition with the Operationalized Psychodynamic Diagnosis Level of Structural Integration Axis (OPD-LSIA) and the Levels of Emotional Awareness Scale (LEAS). In terms of construct validity, a significant association was observed between MAS-A metacognition and a short version of the International Classification of Functioning, Disability and Health (MINI-ICF), which persisted after self-report measures of impairments in structural capacities (Structure Questionnaire of Operationalized Psychodynamic Diagnosis [OPD-SQS]) and mentalizing abilities (Mentalization Questionnaire [MZQ]) were included as covariates, but not after symptom dimensions were included. There was a significant correlation with the current living situation, but not with other external criteria like diagnosis or duration of illness. Future studies should explore alternative outcomes and replicate results in longitudinal designs.

Multisensory Processing Can Compensate for Top-Down Attention Deficits in Schizophrenia.

Studies on schizophrenia (SCZ) and aberrant multisensory integration (MSI) show conflicting results, which are potentially confounded by attention deficits in SCZ. To test this, we examined the interplay between MSI and intersensory attention (IA) in healthy controls (HCs) (N = 27) and in SCZ (N = 27). Evoked brain potentials to unisensory-visual (V), unisensory-tactile (T), or spatiotemporally aligned bisensory VT stimuli were measured with high-density electroencephalography, while participants attended blockwise to either visual or tactile inputs. Behaviorally, IA effects in SCZ, relative to HC, were diminished for unisensory stimuli, but not for bisensory stimuli. At the neural level, we observed reduced IA effects for bisensory stimuli over mediofrontal scalp regions (230-320 ms) in SCZ. The analysis of MSI, using the additive approach, revealed multiple phases of integration over occipital and frontal scalp regions (240-364 ms), which did not differ between HC and SCZ. Furthermore, IA and MSI effects were both positively related to the behavioral performance in SCZ, indicating that IA and MSI mutually facilitate bisensory stimulus processing. Multisensory processing could facilitate stimulus processing and compensate for top-down attention deficits in SCZ. Differences in attentional demands, which may be differentially compensated by multisensory processing, could account for previous conflicting findings on MSI in SCZ.

Effect of standardized post-coercion review session on symptoms of PTSD: results from a randomized controlled trial.

OBJECTIVE: Post-coercion review is increasingly regarded as a mean to reduce the negative consequences of coercive interventions, including the development of posttraumatic symptoms. However, the efficacy of this intervention in preventing posttraumatic symptoms or PTSD has not been sufficiently studied. The objective of this study is to examine the influence of a single, standardized post-coercion review session on the development or exacerbation of PTSD symptoms in patients with psychotic disorders. METHODS: In a multi-center, two-armed, randomized controlled trial, patients who experienced coercive interventions during current hospitalization were either randomized to standard treatment or an intervention group receiving a guideline-based, standardized reflecting review session. Factorial MANCOVA and subsequent ANCOVAs investigated the effects of the post-coercion reflecting review session on post-traumatic symptoms as measured by the subscales of the Impact of Events Scale-Revised (IES-R). Similarly, the effect of the intervention on the intensity of the peritraumatic reactions measured by the Peritraumatic Distress Inventory (PDI) was analyzed by conducting a factorial ANCOVA. RESULTS: N = 82 patients were included in an intention-to-treat analysis. MANCOVA and post hoc ANCOVAs revealed a significant main effect of the intervention for the IES-R subscales intrusion and hyperarousal, when controlling for levels of peritraumatic distress, whereby intervention group participants presented lower respective mean scores. There was no significant difference regarding the intensity of the peritraumatic reaction. CONCLUSION: Standardized post-coercion review contributes to a reduction of the burden of PTSD symptoms in patients with psychotic disorders experiencing coercive interventions in acute settings and shall be recommended as a measure of trauma-informed care. The trial was registered at ClinicalTrials.gov (ID NCT03512925) on 01/30/2018 (retrospectively registered).

Correction to: Migration and schizophrenia: meta-analysis and explanatory framework.

In the original article, the reference number #36 is listed with the wrong list of authors. The first author was unfortunately omitted. The correct reference #36 should read: Lasalvia A, Bonetto C, Tosato S, Cristofalo D, Salazzari D et al (2014) First-contact incidence of psychosis in north-eastern Italy: influence of age, gender, immigration and socioeconomic deprivation. Br J Psychiatry 205:127-134. https://doi.org/10.1192/bjp.bp.113.134445 .Additionally, this reference is cited in Table 1 and Fig. 2 as "Bonetto (2015)" and the correct citation is "Lasalvia (2014)".

Migration and schizophrenia: meta-analysis and explanatory framework.

Systematic reviews and meta-analyses suggest that there are increased rates of schizophrenia and related psychoses in first- and second-generation migrants and refugees. Here, we present a meta-analysis on the incidence of non-affective psychotic disorders among first- and second-generation migrants. We found substantial evidence for an increased relative risk of incidence among first- and second-generation migrants compared to the native population. As heterogeneity of included studies was high, effect estimates should be interpreted with caution and as guiding values rather than exact risk estimates. We interpret our findings in the context of social exclusion and isolation stress, and provide an explanatory framework that links cultural differences in verbal communication and experienced discrimination with the emergence of psychotic experiences and their neurobiological correlates. In this context, we discuss studies observing stress-dependent alterations of dopamine neurotransmission in studies among migrants versus non-migrants as well as in subjects with psychotic disorders. We suggest that social stress effects can impair contextualization of the meaning of verbal messages, which can be accounted for in Bayesian terms by a reduced precision of prior beliefs relative to sensory data, causing increased prediction errors and resulting in a shift towards the literal or "concrete" meaning of words. Compensatory alterations in higher-level beliefs, e.g., in the form of generalized interpretations of ambiguous interactions as hostile behavior, may contribute to psychotic experiences in migrants. We thus suggest that experienced discrimination and social exclusion is at the core of increased rates of psychotic experiences in subjects with a migration background.

Between a rock and a hard place: Associations between Mentzos' "dilemma", self-reported interpersonal problems, and psychosocial functioning in individuals with non-affective psychoses.

Primary aim of this study was to determine the extent and type of self-reported interpersonal problems in patients with non-affective psychoses and their impact on psychosocial functioning. Furthermore, we aimed to explore potential links with the psychodynamic construct of Stavros Mentzos' "psychotic dilemma", which describes an insufferable inner tension caused by an individual's struggle of being torn between "self-oriented" and "object-oriented" tendencies. In a cross-sectional study among 129 patients with non-affective psychoses, measures of cognition, symptom load and social functioning as well as a tentative, psychodynamic assessment of Mentzos' "dilemma" were obtained during a clinical research visit. Self-report data on interpersonal problems were gathered using the Inventory of Interpersonal Problems (IIP-64D) and compared with a German representative standard sample. Second, IIP-64D scores were compared between groups with or without Mentzos' "dilemma". Hierarchical regression analyses were performed to test for the impact of interpersonal problems on psychosocial functioning, while controlling for cognitive deficits and psychopathology. Results showed that IIP-64D scores differed significantly from healthy controls, except for "self-centred" and "intrusive" interpersonal styles. Participants with a potential "psychotic dilemma" scored significantly higher on the subscales: "domineering", "self-centred", "cold", and "socially avoidant" than the group without a "psychotic dilemma". The total amount of interpersonal problems, and particularly high scores on the IIP-64D "socially avoidant" subscale, predicted psychosocial dysfunction, whereas a "cold" interpersonal style had an opposite effect. In conclusion, specific interpersonal problems may predict psychotherapeutic outcome measures like psychosocial functioning and are partly compatible with the psychodynamic construct of Stavros Mentzos' "psychotic dilemma".

[Therapeutic attitudes and structures in (open) acute psychiatry: the Wedding model]. / Therapeutische Haltung und Strukturen in der (offenen) Akutpsychiatrie: das Weddinger Modell.

The Wedding model is a recovery-orientated treatment model that was implemented in 2010 as part of a complex change project in the Department of Psychiatry of the Charité at the St. Hedwig Hospital (PUK-SHK). According to this model, all ward structures were changed in order to promote transparency, participation, trialogue and multiprofessional work. A strong focus was also laid on therapeutic attitudes and the opening of acute psychiatric wards. The relevance of the Wedding model as a possible tool to implement a recovery-orientated, person-centered approach of care and its possible role in the reduction of coercion are the subject of this article.

[Contributions to reduce coercion in psychiatric care]. / Beiträge zur Vermeidung von Zwang in der Akutpsychiatrie.

Reduction in coercion in psychiatric treatment requires successful interaction between changes in structural preconditions and therapeutic processes, as well as in individual therapeutic skills and attitudes. The article gives an overview of current approaches and possibilities to minimize the use of coercive interventions and to create non-violent and participative therapeutic settings. These opportunities are discussed against the background of structural and staff resources, social and legal aspects, as well as subjective experience of patients and their right to protection and treatment in phases when freedom of will and self- determination are compromised.

The influence of coercive measures on patients' stances towards psychiatric institutions.

OBJECTIVE: To examine the impact of coercive interventions (CI) on patients' evaluations of psychiatric hospitals as adversaries versus allies. METHODS: Self-constructed interviews were conducted relating to quantitative and subjective aspects of coercion and the attitude towards psychiatry of 79 patients with psychotic and bipolar disorders. The Coercion Experience Scale (CES) and the Admission Experience Survey (AES) were used to establish the subjective impact of CI. Instruments measuring psychopathological symptoms and the Global Assessment of Functioning (GAF) were applied alongside the Schedule for the Assessment of Illness (SAI) and the Beck Cognitive Insight Scale (BCIS). Using a logistic regression approach, considered influencing factors such as number, type and patients' subjective experiences of CI, cognitive and clinical insight, psychopathological symptoms and patients' global perceptions of their hospitalisation were analysed for their predictive value of patients' attitudes towards psychiatry. RESULTS: Binary logistic regression revealed that the subjective experience of CI and the perception of fairness and effectiveness during the treatment process predict patients' attitudes towards psychiatry to a greater extent than symptom-related measures or the quantity of CI. Patients presenting a higher degree of self-reflectiveness perceive psychiatric institutions more likely as allies. CONCLUSIONS: The manner in which coercion is subjectively experienced has direct influence on patients' perceptions of psychiatry.

Attentional dysfunction in abstinent long-term cannabis users with and without schizophrenia.

Long-term cannabis use may confer cognitive deficits and increased risk of psychosis. However, the relationship between cannabis use and schizophrenia is complex. In particular, little is known about the effects of chronic cannabis use on the attention-related electric brain response in schizophrenia. We investigated auditory novelty and oddball P300 evoked potentials in a mixed sample of first-episode and chronic schizophrenic patients and healthy controls with (SZCA, n = 20; COCA, n = 20, abstinence ≥28 days) or without (SZ, n = 20; CO, n = 20) chronic cannabis use. Duration of regular cannabis use was 8.3 ± 5.6 (SZCA) and 9.1 ± 7.1 (COCA) years. In general, schizophrenic patients showed reduced P300 amplitudes. Cannabis use was associated with both a reduced early and late left-hemispheric novelty P300. There was a significant 'diagnosis × cannabis' interaction for the left-hemispheric late novelty P300 in that cannabis use was associated with a reduced amplitude in the otherwise healthy but not in the schizophrenic group compared with their relative control groups (corrected p < 0.02; p > 0.9, respectively). The left-hemispheric late novelty P300 in the otherwise healthy cannabis group correlated inversely with amount and duration of cannabis use (r = -0.50, p = 0.024; r = -0.57, p = 0.009, respectively). Our study confirms attentional deficits with chronic cannabis use. However, cannabis use may lead to different cognitive sequelae in patients with schizophrenia and in healthy controls, possibly reflecting preexisting alterations in the endocannabinoid system in schizophrenia.

Adding a Piece to the Puzzle? The Allocation of Figurative Language Comprehension into the CHC Model of Cognitive Abilities.

The study aimed to investigate the allocation of figurative language comprehension (FLC) within the Cattell-Horn-Carroll (CHC) model of cognitive abilities, using three newly developed tests: the Reverse Paraphrase Test (RPT), the Literal Paraphrase Test (LPT), and the Proverb Test (PT). The analysis of a sample of 909 participants revealed that the RPT and LPT measured a unidimensional construct of FLC, while the PT was excluded due to insufficient fit. Combining RPT and LPT items, various models were evaluated, with a bifactor S-1 model showing the best fit, indicating the influence of a general factor (representing FLC) and test-specific method factors. The study explored FLC allocation within the CHC model, supporting its consideration as a distinct factor under the g factor. Examining the nomological network, significant correlations emerged between the Intellectual Curiosity and Aesthetic Sensitivity facets of Openness and FLC, which were comparable in size to the relation with general ability. In conclusion, the study enhances the understanding of FLC within the CHC model, advocating its recognition as a distinct factor. Correlations with Openness facets suggest valuable insights into the interplay between cognitive abilities and personality, necessitating further research for a deeper exploration of this relation.

Level of structural integration in people with schizophrenia and schizoaffective disorders - applicability and associations with clinical parameters.

Introduction: The psychic structure of people with psychosis has been the subject of theoretical and qualitative considerations. However, it has not been sufficiently studied quantitatively. Therefore, the aim of this study was to explore the structural abilities of people diagnosed with schizophrenia and schizoaffective psychosis using the Levels of Structural Integration Axis of the Operationalized Psychodynamic Diagnosis System (OPD-2-LSIA). The study aimed to determine possible associations between the OPD-2-LSIA and central parameters of illness. Additionally, possible structural differences between people diagnosed with schizophrenia and schizoaffective psychosis were tested. Methods: This cross-sectional study included 129 outpatients with schizophrenia or schizoaffective disorders. Measures of structural integration, symptom load, severity of illness, cognition, and social functioning were obtained. Descriptive statistics were used to analyze the overall structural level and the structural dimensions. Correlation coefficients were computed to measure the associations between OPD-2-LSIA and variables regarding the severity of illness and psychosocial functioning. Regression models were used to measure the influence of illness-related variables on OPD-2-LSIA, and the influence of OPD-2-LSIA on psychosocial functioning. Participants diagnosed with schizophrenia and schizoaffective disorders were examined with regard to possible group differences. Results: The results of the OPD-2-LSIA showed that the overall structural level was between 'moderate to low' and 'low level of structural integration'. Significant correlations were found between OPD-2-LSIA and psychotic symptoms (but not depressive symptoms), as well as between OPD-2-LSIA and psychosocial functioning. It was found that variables related to severity of illness had a significant impact on OPD-2-LSIA, with psychotic, but not depressive symptoms being significant predictors. OPD-2-LSIA was found to predict psychosocial functioning beyond symptoms and cognition. No significant differences were found between participants with schizophrenia and schizoaffective psychosis. There was also no correlation found between OPD-2-LSIA and depressive symptomatology (except for the subdimension Internal communication). Discussion: Contrary to theoretical assumptions, the results of the study show a heterogenous picture of the psychic structure of people with psychosis. The associations between OPD-2-LSIA and severity of illness, particularly psychotic symptomatology, as well as the influence of OPD-2-LSIA on psychosocial functioning, are discussed.

Linguistic findings in persons with schizophrenia-a review of the current literature.

Introduction: Alterations of verbalized thought occur frequently in psychotic disorders. We characterize linguistic findings in individuals with schizophrenia based on the current literature, including findings relevant for differential and early diagnosis. Methods: Review of literature published via PubMed search between January 2010 and May 2022. Results: A total of 143 articles were included. In persons with schizophrenia, language-related alterations can occur at all linguistic levels. Differentiating from findings in persons with affective disorders, typical symptoms in those with schizophrenia mainly include so-called "poverty of speech," reduced word and sentence production, impaired processing of complex syntax, pragmatic language deficits as well as reduced semantic verbal fluency. At the at-risk state, "poverty of content," pragmatic difficulties and reduced verbal fluency could be of predictive value. Discussion: The current results support multilevel alterations of the language system in persons with schizophrenia. Creative expressions of psychotic experiences are frequently found but are not in the focus of this review. Clinical examinations of linguistic alterations can support differential diagnostics and early detection. Computational methods (Natural Language Processing) may improve the precision of corresponding diagnostics. The relations between language-related and other symptoms can improve diagnostics.

Mentalizing in the context of Mentzos' dilemma-on the use of implicit work in the treatment of non-affective psychosis.

Current approaches to the treatment of non-affective psychosis include elements of mentalization-based treatment and the potential in enhancing mentalizing capacity in this patient group has been widely emphasized. This article presents the "psychotic identity dilemma", a concept by Stavros Mentzos, and a therapeutic approach considering this concept as a valuable complementary addition to these treatments. The idea of a dilemma between closeness and distance, which in itself cannot be represented mentally at first, helps to respond to specific needs of patients with psychotic disorders by placing the treatment focus on fundamental interpersonal processes. Following this train of thought, this article attempts to shed light on the importance of the "real relationship" between therapist and patient as well as the exploration of the "here and now", especially at the beginning of psychotherapeutic treatment. Two treatment modes are suggested, one characterized by the experience of interpersonality within the therapeutic relationship and a second one characterized by the reflection of interpersonal phenomena. These modes are framed by Stavros Mentzos' concept of an identity dilemma. We describe how mentalizing first needs to be addressed implicitly in a tolerable, exemplary relationship in which closeness and distance are regulated based on the therapist's countertransference, then explicitly. A series of interventions are described, which allow for moments of shared attention, promote intentionality and contingency and, later in the course of therapy, help to integrate experiences into narratives.

Validation of natural language processing methods capturing semantic incoherence in the speech of patients with non-affective psychosis.

Background: Impairments in speech production are a core symptom of non-affective psychosis (NAP). While traditional clinical ratings of patients' speech involve a subjective human factor, modern methods of natural language processing (NLP) promise an automatic and objective way of analyzing patients' speech. This study aimed to validate NLP methods for analyzing speech production in NAP patients. Methods: Speech samples from patients with a diagnosis of schizophrenia or schizoaffective disorder were obtained at two measurement points, 6 months apart. Out of N = 71 patients at T1, speech samples were also available for N = 54 patients at T2. Global and local models of semantic coherence as well as different word embeddings (word2vec vs. GloVe) were applied to the transcribed speech samples. They were tested and compared regarding their correlation with clinical ratings and external criteria from cross-sectional and longitudinal measurements. Results: Results did not show differences for global vs. local coherence models and found more significant correlations between word2vec models and clinically relevant outcome variables than for GloVe models. Exploratory analysis of longitudinal data did not yield significant correlation with coherence scores. Conclusion: These results indicate that natural language processing methods need to be critically validated in more studies and carefully selected before clinical application.

Predicting psychotic relapse following randomised discontinuation of paliperidone in individuals with schizophrenia or schizoaffective disorder: an individual participant data analysis.

BACKGROUND: Predicting relapse for individuals with psychotic disorders is not well established, especially after discontinuation of antipsychotic treatment. We aimed to identify general prognostic factors of relapse for all participants (irrespective of treatment continuation or discontinuation) and specific predictors of relapse for treatment discontinuation, using machine learning. METHODS: For this individual participant data analysis, we searched the Yale University Open Data Access Project's database for placebo-controlled, randomised antipsychotic discontinuation trials with participants with schizophrenia or schizoaffective disorder (aged ≥18 years). We included studies in which participants were treated with any antipsychotic study drug and randomly assigned to continue the same antipsychotic drug or to discontinue it and receive placebo. We assessed 36 prespecified baseline variables at randomisation to predict time to relapse, using univariate and multivariate proportional hazard regression models (including multivariate treatment group by variable interactions) with machine learning to categorise the variables as general prognostic factors of relapse, specific predictors of relapse, or both. FINDINGS: We identified 414 trials, of which five trials with 700 participants (304 [43%] women and 396 [57%] men) were eligible for the continuation group and 692 participants (292 [42%] women and 400 [58%] men) were eligible for the discontinuation group (median age 37 [IQR 28-47] years for continuation group and 38 [28-47] years for discontinuation group). Out of the 36 baseline variables, general prognostic factors of increased risk of relapse for all participants were drug-positive urine; paranoid, disorganised, and undifferentiated types of schizophrenia (lower risk for schizoaffective disorder); psychiatric and neurological adverse events; higher severity of akathisia (ie, difficulty or inability to sit still); antipsychotic discontinuation; lower social performance; younger age; lower glomerular filtration rate; benzodiazepine comedication (lower risk for anti-epileptic comedication). Out of the 36 baseline variables, predictors of increased risk specifically after antipsychotic discontinuation were increased prolactin concentration, higher number of hospitalisations, and smoking. Both prognostic factors and predictors with increased risk after discontinuation were oral antipsychotic treatment (lower risk for long-acting injectables), higher last dosage of the antipsychotic study drug, shorter duration of antipsychotic treatment, and higher score on the Clinical Global Impression (CGI) severity scale The predictive performance (concordance index) for participants who were not used to train the model was 0·707 (chance level is 0·5). INTERPRETATION: Routinely available general prognostic factors of psychotic relapse and predictors specific for treatment discontinuation could be used to support personalised treatment. Abrupt discontinuation of higher dosages of oral antipsychotics, especially for individuals with recurring hospitalisations, higher scores on the CGI severity scale, and increased prolactin concentrations, should be avoided to reduce the risk of relapse. FUNDING: German Research Foundation and Berlin Institute of Health.

Investigating the relationship between negative symptoms and metacognitive functioning in psychosis: An individual participant data meta-analysis.

PURPOSE: Negative symptoms are a persistent, yet under-explored problem in psychosis. Disturbances in metacognition are a potential causal factor in negative symptom development and maintenance. This meta-analysis uses individual participant data (IPD) from existing research to assess the relationship between negative symptoms and metacognition treated as summed scores and domains. METHODS: Data sets containing individuals with negative symptoms and metacognition data, aged 16+ with psychosis, were identified according to pre-specific parameters. IPD integrity and completeness were checked and data were synthesized in two-stage meta-analyses of each negative symptoms cluster compared with metacognition in seemingly unrelated regression using restricted maximum likelihood estimation. Planned and exploratory sensitivity analyses were also conducted. RESULTS: Thirty-three eligible data sets were identified with 21 with sufficient similarity and availability to be included in meta-analyses, corresponding to 1301 participants. The strongest relationships observed were between summed scores of negative symptoms and metacognition. Metacognitive domains of self-reflectivity and understanding others' minds, and expressive negative symptoms emerged as significant in some meta-analyses. The uncertainty of several effect estimates increased significantly when controlling for covariates. CONCLUSIONS: This robust meta-analysis highlights the impact of using summed versus domain-specific scores of metacognition and negative symptoms, and relationships are not as clear-cut as once believed. Findings support arguments for further differentiation of negative symptom profiles and continued granular exploration of the relationship between metacognition and negative symptoms.