Obsessive-compulsive symptoms relating to psychosocial functioning for people with schizophrenia, schizoaffective disorder, or bipolar disorder.

To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25-1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22-1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22-1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.

Long-Term Changes in Cognition Among Patients With Schizophrenia Spectrum Disorders and Different Durations of Illness: A Meta-Analysis.

Objective: In this meta-analysis, we evaluated changes in cognition for patients with schizophrenia spectrum disorders (SSD) with different durations of illness (DOIs).Data Sources: Records were identified through searches in PubMed, PsycINFO, CINAHL, and Cochrane until December 2021. We used terms related to SSDs, chronicity, course, and recovery.Study Selection and Data Extraction: We included 57 longitudinal studies, with a follow-up length of at least 1 year, investigating changes in 10 domains of cognition of patients who are all diagnosed with SSD. Changes in cognition were analyzed through effect sizes of change between baseline and follow-up assessments within each study. These changes were evaluated in different subgroups of studies including patients with a DOI <5 years, 5-10 years, or >10 years. We also investigated the influence of 19 potential moderators on these changes in cognition.Results: We found marginal improvements in overall cognition (d =0.13), small improvements in verbal memory (d = 0.21), processing speed (d = 0.32), marginal improvements in visual memory (d = 0.17), executive functioning (d = 0.19), and language skills (d = 0.13), and no significant improvements in the other cognitive domains. The largest improvements were achieved for patients with a DOI <10 years. Changes are more favorable for patients with a younger age, no schizophrenia diagnosis, female gender, higher education level, and low negative symptom severity.Conclusions: We observed only modest cognitive improvement in SSD almost exclusively in patients with early psychosis. Future research should focus on optimizing interventions targeting cognition in specific subgroups and the interrelationships with other life domains.

Multivariable prediction of functional outcome after first-episode psychosis: a crossover validation approach in EUFEST and PSYSCAN.

Several multivariate prognostic models have been published to predict outcomes in patients with first episode psychosis (FEP), but it remains unclear whether those predictions generalize to independent populations. Using a subset of demographic and clinical baseline predictors, we aimed to develop and externally validate different models predicting functional outcome after a FEP in the context of a schizophrenia-spectrum disorder (FES), based on a previously published cross-validation and machine learning pipeline. A crossover validation approach was adopted in two large, international cohorts (EUFEST, n = 338, and the PSYSCAN FES cohort, n = 226). Scores on the Global Assessment of Functioning scale (GAF) at 12 month follow-up were dichotomized to differentiate between poor (GAF current < 65) and good outcome (GAF current ≥ 65). Pooled non-linear support vector machine (SVM) classifiers trained on the separate cohorts identified patients with a poor outcome with cross-validated balanced accuracies (BAC) of 65-66%, but BAC dropped substantially when the models were applied to patients from a different FES cohort (BAC = 50-56%). A leave-site-out analysis on the merged sample yielded better performance (BAC = 72%), highlighting the effect of combining data from different study designs to overcome calibration issues and improve model transportability. In conclusion, our results indicate that validation of prediction models in an independent sample is essential in assessing the true value of the model. Future external validation studies, as well as attempts to harmonize data collection across studies, are recommended.

Psychiatrists effect on positive symptom severity and daily functioning during pharmacotherapy for first-episode psychosis patients.

Clinical outcomes after a first-episode of psychosis (FEP) are heterogeneous. Many patient-related factors such as gender and comorbidity have been studied to predict symptomatic outcomes. However, psychiatrist-related factors such as prescription behaviour and gender have received little attention. We assessed the relationship between patients' psychiatrists, psychosis severity and daily functioning in 201 patients remitted from an FEP for a duration of one year, treated by 18 different psychiatrists. We controlled for baseline severity, dose and type of antipsychotic medication, frequency of visits, and patients' education. Symptom severity, daily functioning, and antipsychotic drug use were assessed at baseline and at 3, 6, and, 12 months follow-up. We found that psychiatrists accounted for 9.1% of the explained variance in patients' symptom severity and 10.1% of the explained variance in daily functioning.These effects persisted even when controlling for factors such as baseline severity and the prescribed dose. The effect of prescribed dose on symptom severity and daily functioning differed between psychiatrists. Treatment centre, session frequency, and medication nonadherence were not related to symptom severity. Our results emphasize the importance of individual psychiatrist factors in symptomatic outcomes after an FEP. Further identification of psychiatrist-related factors such as the quality of therapeutic alliances and shared decision-making, may optimize psychiatrists' training with the goal of improving patient outcomes.

Methylomic signature of current cannabis use in two first-episode psychosis cohorts.

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.

Exploring the Interactions Between Psychotic Symptoms, Cognition, and Environmental Risk Factors: A Bayesian Analysis of Networks.

BACKGROUND AND HYPOTHESIS: Psychotic disorders (PDs) have huge personal and societal impact, and efforts to improve outcomes in patients are continuously needed. Environmental risk factors (ERFs), especially modifiable risk factors, are important to study because they pose a target for intervention and prevention. No studies have investigated ERFs, cognition, and psychotic symptoms together in a network approach. STUDY DESIGN: We explored interactions between 3 important ERFs (tobacco smoking, cannabis use, and childhood trauma), 6 cognitive domains, and 3 dimensions of symptoms in psychosis. From the Genetic Risk and Outcome of Psychosis (GROUP) cohort, we used data from patients, siblings, and healthy controls to construct networks using Bayesian analyses of all 12 variables. We constructed networks of the combined sample and of patients and siblings separately. STUDY RESULTS: We found that tobacco smoking was directly associated with cognition and psychotic symptoms. The cognitive variable processing speed was the most central node, connecting clusters of psychotic symptoms and substance use through the variables of positive symptoms and tobacco smoking. Comparing the networks of patients and siblings, we found that networks were relatively similar between patients and siblings. CONCLUSIONS: Our results support a potential central role of processing speed deficits in PDs. Findings highlight the importance of integrating tobacco smoking as potential ERFs in the context of PDs and to broaden the perspective from cannabis discontinuation to smoking cessation programs in patients or people at risk of PDs.

Development and temporal validation of a clinical prediction model of transition to psychosis in individuals at ultra-high risk in the UHR 1000+ cohort.

The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets have now been integrated into the UHR 1000+ cohort, consisting of a sample of 1,245 UHR individuals with a follow-up period ranging from 1 to 16.7 years. This paper describes the cohort, presents a clinical prediction model of transition to psychosis in this cohort, and examines how predictive performance is affected by changes in UHR samples over time. We analyzed transition to psychosis using a Cox proportional hazards model. Clinical predictors for transition to psychosis were investigated in the entire cohort using multiple imputation and Rubin's rule. To assess performance drift over time, data from 1995-2016 were used for initial model fitting, and models were subsequently validated on data from 2017-2020. Over the follow-up period, 220 cases (17.7%) developed a psychotic disorder. Pooled hazard ratio (HR) estimates showed that the Comprehensive Assessment of At-Risk Mental States (CAARMS) Disorganized Speech subscale severity score (HR=1.12, 95% CI: 1.02-1.24, p=0.024), the CAARMS Unusual Thought Content subscale severity score (HR=1.13, 95% CI: 1.03-1.24, p=0.009), the Scale for the Assessment of Negative Symptoms (SANS) total score (HR=1.02, 95% CI: 1.00-1.03, p=0.022), the Social and Occupational Functioning Assessment Scale (SOFAS) score (HR=0.98, 95% CI: 0.97-1.00, p=0.036), and time between onset of symptoms and entry to UHR service (log transformed) (HR=1.10, 95% CI: 1.02-1.19, p=0.013) were predictive of transition to psychosis. UHR individuals who met the brief limited intermittent psychotic symptoms (BLIPS) criteria had a higher probability of transitioning to psychosis than those who met the attenuated psychotic symptoms (APS) criteria (HR=0.48, 95% CI: 0.32-0.73, p=0.001) and those who met the Trait risk criteria (a first-degree relative with a psychotic disorder or a schizotypal personality disorder plus a significant decrease in functioning during the previous year) (HR=0.43, 95% CI: 0.22-0.83, p=0.013). Models based on data from 1995-2016 displayed good calibration at initial model fitting, but showed a drift of 20.2-35.4% in calibration when validated on data from 2017-2020. Large-scale longitudinal data such as those from the UHR 1000+ cohort are required to develop accurate psychosis prediction models. It is critical to assess existing and future risk calculators for temporal drift, that may reduce their utility in clinical practice over time.

Electroconvulsive Therapy Versus Aripiprazole Addition to Clozapine in Patients with Clozapine-Resistant Symptoms (EMECLO): A Protocol of a Single-Blind, Multicenter, Randomized-Controlled Feasibility Trial.

BACKGROUND: Currently, guidance on the most effective treatment for patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is lacking. While augmentation strategies to clozapine with aripiprazole and electroconvulsive therapy (ECT) have been demonstrated to be effective in patients with clozapine-resistant schizophrenia spectrum disorders (CRS), head-to-head comparisons between these addition strategies are unavailable. We therefore aim to examine the feasibility of a larger randomized, single-blind trial comparing the effectiveness, cost-effectiveness, and safety of aripiprazole addition vs. ECT addition in CRS. METHODS: In this multi-center, randomized, single-blind feasibility study, the feasibility of recruiting 20 participants with CRS who will be randomized to either aripiprazole or bilateral ECT addition will be assessed. The main endpoint is the number of patients willing to be randomized. The number of screened individuals and reasons to decline participation will be recorded. Effects will be estimated for the benefit of the foreseen larger trial. To that end, differences between both arms in symptom severity will be assessed using blinded video assessments. In addition, tolerability (e. g., cognitive functioning), safety, quality of life, recovery, and all-cause discontinuation will be compared. The follow-up period is 16 weeks, after which non-responders will be given the option to switch to the other treatment. DISCUSSION: Strengths of this feasibility trial include maintaining blinding with video assessment, a possibility to switch groups in case of non-response, and a broad set of outcome measures. Identification of factors contributing to non-participation and drop-out will generate valuable information on trial feasibility and may enhance recruitment strategies in a follow-up RCT. TRIAL REGISTRATION: The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Center, location AMC, and was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under the trial name 'EMECLO' (2021-006333-19).

The association of tobacco smoking and metabolite levels in the anterior cingulate cortex of first-episode psychosis patients: A case-control and 6-month follow-up 1H-MRS study.

Tobacco smoking is highly prevalent among patients with psychosis and associated with worse clinical outcomes. Neurometabolites, such as glutamate and choline, are both implicated in psychosis and tobacco smoking. However, the specific associations between smoking and neurometabolites have yet to be investigated in patients with psychosis. The current study examines associations of chronic smoking and neurometabolite levels in the anterior cingulate cortex (ACC) in first-episode psychosis (FEP) patients and controls. Proton magnetic resonance spectroscopy (1H MRS) data of 59 FEP patients and 35 controls were analysed. Associations between smoking status (i.e., smoker yes/no) or cigarettes per day and Glx (glutamate + glutamine, as proxy for glutamate) and total choline (tCh) levels were assessed at baseline in both groups separately. For patients, six months follow-up data were acquired for multi-cross-sectional analysis using linear mixed models. No significant differences in ACC Glx levels were found between smoking (n = 28) and non-smoking (n = 31) FEP patients. Smoking patients showed lower tCh levels compared to non-smoking patients at baseline, although not surving multiple comparisons correction, and in multi-cross-sectional analysis (pFDR = 0.08 and pFDR = 0.044, respectively). Negative associations were observed between cigarettes smoked per day, and ACC Glx (pFDR = 0.02) and tCh levels (pFDR = 0.02) in controls. Differences between patients and controls regarding Glx might be explained by pre-existing disease-related glutamate deficits or alterations at nicotine acetylcholine receptor level, resulting in differences in tobacco-related associations with neurometabolites. Additionally, observed alterations in tCh levels, suggesting reduced cellular proliferation processes, might result from exposure to the neurotoxic effects of smoking.

Clozapine levels and outcomes in Serbian patients with treatment-resistant psychotic disorders previously treated without measuring clozapine levels (CLOSER).

Clozapine remains the only pharmacological treatment option for treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) of clozapine is recommended, although evidence for the therapeutic range of 350-600 ng/ml is limited. In various countries including Serbia, TDM of clozapine is not routinely performed. This study evaluated the distribution of clozapine levels and their relationship with clinical outcomes in Serbian patients who had not undergone prior TDM. 140 Patients with treatment-resistant schizophrenia and schizo-affective disorder were enrolled. Clozapine levels were measured by dried blood spot (DBS) analysis. Side effects were evaluated by GASS-c, severity of symptoms and functional impairment with WHODAS, CGI-S and GAF. Of the patients, 51.2% had subtherapeutic levels, 24.8% were in the therapeutic window, and 24% had supratherapeutic levels. Clozapine levels showed no association with side effects and a weak positive association with symptom severity and functional impairment. No serious side effects were observed in patients with clozapine levels surpassing 1000 ng/ml (n = 8). Based on these findings, we propose that the upper limit of the therapeutic range should not be regarded as an absolute barrier, and guidelines should allow for a personalized approach when prescribing clozapine.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Do Cognitive Subtypes Exist in People at Clinical High Risk for Psychosis? Results From the EU-GEI Study.

BACKGROUND AND HYPOTHESIS: Cognition has been associated with socio-occupational functioning in individuals at Clinical High Risk for Psychosis (CHR-P). The present study hypothesized that clustering CHR-P participants based on cognitive data could reveal clinically meaningful subtypes. STUDY DESIGN: A cohort of 291 CHR-P subjects was recruited through the multicentre EU-GEI high-risk study. We explored whether an underlying cluster structure was present in the cognition data. Clustering of cognition data was performed using k-means clustering and density-based spatial clustering of applications with noise. Cognitive subtypes were validated by comparing differences in functioning, psychosis symptoms, transition outcome, and grey matter volume between clusters. Network analysis was used to further examine relationships between cognition scores and clinical symptoms. STUDY RESULTS: No underlying cluster structure was found in the cognitive data. K-means clustering produced "spared" and "impaired" cognition clusters similar to those reported in previous studies. However, these clusters were not associated with differences in functioning, symptomatology, outcome, or grey matter volume. Network analysis identified cognition and symptoms/functioning measures that formed separate subnetworks of associations. CONCLUSIONS: Stratifying patients according to cognitive performance has the potential to inform clinical care. However, we did not find evidence of cognitive clusters in this CHR-P sample. We suggest that care needs to be taken in inferring the existence of distinct cognitive subtypes from unsupervised learning studies. Future research in CHR-P samples could explore the existence of cognitive subtypes across a wider range of cognitive domains.

Making Sense of Recovery From First Psychosis With Antipsychotic Medication: A Qualitative Phenomenological Study.

BACKGROUND AND HYPOTHESIS: Recovering from a first psychosis is a highly individual process and requires the person to make sense of their experiences. Clinicians, in turn, need to comprehend these first-person perspectives, creating a mutual sense-making dynamic. Antipsychotic medication is a substantial part of psychosis treatment. Providing insight in the lived experience of recovery with antipsychotics could improve the mutual understanding and help bridge the gap between the perspective of the clinician and that of the person recovering from psychosis. STUDY DESIGN: 14 persons in recovery from a first psychosis with the use of antipsychotics were interviewed. Their narratives were analyzed using Interpretative Phenomenological Analysis (IPA). STUDY RESULTS: Five overarching themes were found, representing important and meaningful experiences in recovering with antipsychotic medication. Theme 1: antipsychotics as external dampening (4 subthemes); Theme 2: shifting of realities; Theme 3: pace of recovery; Theme 4: antipsychotics' influence on identity; and Theme 5: is it truly the antipsychotics? CONCLUSIONS: Our findings show that recovery from psychosis with antipsychotics is an all-encompassing, multi-faceted, and ambivalent experience. The themes found in this research could inspire clinicians to discuss less obvious aspects of the experience of recovering with antipsychotics. Even more so, paying attention to the first-person perspective could lead to a more thorough understanding and benefit therapeutic relationships.

The Association Between Chronic Tobacco Smoking and Brain Alterations in Schizophrenia: A Systematic Review of Magnetic Resonance Imaging Studies.

BACKGROUND AND HYPOTHESIS: The high co-occurrence of tobacco smoking in patients with schizophrenia spectrum disorders (SSD) poses a serious health concern, linked to increased mortality and worse clinical outcomes. The mechanisms underlying this co-occurrence are not fully understood. STUDY DESIGN: Addressing the need for a comprehensive overview of the impact of tobacco use on SSD neurobiology, we conducted a systematic review of neuroimaging studies (including structural, functional, and neurochemical magnetic resonance imaging studies) that investigate the association between chronic tobacco smoking and brain alterations in patients with SSD. STUDY RESULTS: Eight structural and fourteen functional studies were included. Structural studies show widespread independent and additive reductions in gray matter in relation to smoking and SSD. The majority of functional studies suggest that smoking might be associated with improvements in connectivity deficits linked to SSD. However, the limited number of and high amount of cross-sectional studies, and high between-studies sample overlap prevent a conclusive determination of the nature and extent of the impact of smoking on brain functioning in patients with SSD. Overall, functional results imply a distinct neurobiological mechanism for tobacco addiction in patients with SSD, possibly attributed to differences at the nicotinic acetylcholine receptor level. CONCLUSIONS: Our findings highlight the need for more longitudinal and exposure-dependent studies to differentiate between inherent neurobiological differences and the (long-term) effects of smoking in SSD, and to unravel the complex interaction between smoking and schizophrenia at various disease stages. This could inform more effective strategies addressing smoking susceptibility in SSD, potentially improving clinical outcomes.

Paralytic ileus in a patient on clozapine therapy showing an inverted clozapine/norclozapine ratio after switching valproic acid to carbamazepine: a case report.

This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case of a 42-year-old patient diagnosed with schizoaffective disorder undergoing clozapine therapy. Despite intensive treatment with clozapine, haloperidol, valproic acid and biweekly electroconvulsive therapy sessions for over a year, florid psychotic symptoms and fluctuating mood swings persisted. Therefore, valproic acid was replaced by carbamazepine, a potent inducer of several CYP450-enzymes. To maintain clozapine plasma levels, fluvoxamine, a CYP1A2-inhibitor, was introduced at a dose of 25 mg before this switch. After addition of carbamazepine, there was a significant decline in clozapine levels, necessitating an increase in fluvoxamine dosage to 50 mg. Five weeks later the patient was admitted to a general hospital with a diagnosis of paralytic ileus. Treatment with enemas proved effective. Drug concentration analysis revealed a 2.5-fold increase in norclozapine levels in the weeks preceding hospital admission, resulting in an inverted clozapine/norclozapine ratio. Treatment with clozapine, carbamazepine and fluvoxamine was continued as the patient demonstrated clinical improvement on carbamazepine. Concurrently, an intensive laxative regimen was initiated. Two weeks later, the patient was readmitted to the general hospital due to suspected paralytic ileus and faecal vomiting, once again displaying an inverted clozapine/norclozapine ratio. We discuss potential mechanisms contributing to the occurrence of the paralytic ileus in this patient, including the antagonism of muscarinic M3 receptors by both clozapine and norclozapine, as well as the agonism of delta-opioid receptors by norclozapine. This case highlights the potential significance of both the clozapine/norclozapine ratio and absolute norclozapine levels as risk factors for constipation and paralytic ileus in patients on clozapine therapy.

The Role of Social Deprivation and Cannabis Use in Explaining Variation in the Incidence of Psychotic Disorders: Findings From the EU-GEI Study.

BACKGROUND AND HYPOTHESIS: Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings. STUDY DESIGN: We used incidence data in people aged 18-64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group. STUDY RESULTS: Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61-0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55-0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02-2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings. CONCLUSIONS: Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders.

Response to psychotic experiences: Impact of personality traits on perceived levels of distress.

BACKGROUND: This study examined the influence of personality traits on (subclinical) positive symptom distress in patients with a psychotic disorder, their unaffected siblings and healthy controls. METHODS: Data were obtained from the Genetic Risk and Outcome of Psychosis study (GROUP), a Dutch longitudinal multicenter cohort study. Data from 140 patients, 216 unaffected siblings and 102 healthy controls was available for baseline levels of Five Factor Model personality traits and frequency and distress due to psychotic experiences three years later, assessed with the Community Assessment of Psychic Experience questionnaire. Main effects of all five personality traits on symptom distress were investigated as well as moderating effects of Neuroticism, Extraversion and Openness on positive symptom frequency and positive symptom distress. Age, gender, symptom frequency and IQ were controlled for. RESULTS: In both patients and siblings, the observed main effects of Neuroticism and Openness on (subclinical) positive symptom distress three years later either lost significance or had a very small effect size when controlling for covariates, mainly due to the correction for the effect of positive symptoms on personality traits at baseline. In both groups, levels of Openness at baseline moderated the association between positive symptom frequency and positive symptom distress three years later, in the direction that higher levels of Openness were associated with weaker associations between positive symptom frequency and - distress, even when covariates were controlled for. DISCUSSION: The level of Openness to Experiences influences the perceived distress from (subclinical) positive symptoms in both patients and siblings.

Long-term Changes in Personal Recovery and Quality of Life Among Patients With Schizophrenia Spectrum Disorders and Different Durations of Illness: A Meta-analysis.

BACKGROUND AND HYPOTHESIS: In schizophrenia spectrum disorders (SSD) personal recovery and subjective quality of life (S-QOL) are crucial and show conceptual overlap. There is limited knowledge about how these outcomes change over time. Therefore, we investigated changes in personal recovery or S-QOL for patients with SSD. We specifically focused on the influence of the patients' durations of illness (DOI) on changes in personal recovery and S-QOL. STUDY DESIGN: We included 46 studies investigating longitudinal changes in quantitative assessments of personal recovery or S-QOL for patients with SSD. Outcomes were categorized in overall personal recovery, overall S-QOL connectedness, hope and optimism, identity, meaning in life, and empowerment. We evaluated effect sizes of change between baseline and follow-up assessments. We also evaluated potential moderating effects, including DOI on these changes in outcomes. STUDY RESULTS: We found small improvements of overall personal recovery and S-QOL, but marginal or no improvement over time in the other more specific outcome domains. Patients without a schizophrenia diagnosis, a younger age, and more recent publications positively influenced these changes. We found no significant influence of DOI on the changes in any outcome domain. CONCLUSIONS: Improvement in personal recovery or S-QOL of people with SSD is modest at best. However, these studies did not fully capture the personal narratives or nonlinear process of recovery of an individual. Future research should focus on how to shift from a clinical to more person-oriented approach in clinical practice to support patients in improving their personal process of recovery. REVIEW PROTOCOL REGISTRATION: CRD42022377100.