Brief admission by self-referral as an add-on to usual care for individuals with self-harm at risk of suicide: cost-effectiveness and 4-year health-economic consequences after a Swedish randomized controlled trial.

BACKGROUND: Brief Admission by self-referral (BA) is a crisis-management intervention standardized for individuals with self-harm at risk of suicide. We analyzed its health-economic consequences. MATERIALS AND METHODS: BA plus treatment as usual (TAU) was compared with TAU alone in a 12-month randomized controlled trial with 117 participants regarding costs for hospital admissions, coercive measures, emergency care and health outcomes (quality-adjusted life years; QALYs). Participants were followed from 12 months before baseline to up to five years after. RESULTS: Over one year BA was associated with a mean annual cost reduction of 4800 or incremental cost of 4600 euros, depending on bed occupancy assumption. Cost-savings were greatest for individuals with >180 admission days in the year before baseline. In terms of health outcomes BA was associated with a QALY gain of 0.078. Uncertainty analyses indicated a significant QALY gain and ambiguity in costs, resulting in BA either dominating TAU or costing 59 000 euros per gained QALY. CONCLUSION: BA is likely to produce QALY gains for individuals living with self-harm and suicidality. Cost-effectiveness depends on targeting high-need individuals and comparable bed utilization between BA and other psychiatric admissions. Future research should elaborate the explanatory factors for individual variations in the usage and benefit of BA.

Psychiatry Nurses' Experiences of Patient-Initiated Brief Admission from Inpatient and Outpatient Perspectives: A Qualitative Exploratory Study.

Patient-initiated brief admission (PIBA) allows patients to decide when admission to psychiatric care is necessary. This may prevent long-term hospitalisation and promote patient participation. Research on psychiatric nurses' experiences with PIBA is lacking, therefore 11 nurses were interviewed and data analysed using content analysis. Prominent categories were: improved personal development for the patient, more equal nurse-patient relationship, rapid access to a safe environment and strengthened professional collaboration. PIBA is a helpful intervention for patients in crisis, giving both patients and nurses a sense of security. Future studies should explore how this impacts nurses' work environment and job satisfaction.

Patient-Initiated Brief Admission for Individuals with Emotional Instability and Self-Harm: An Evaluation of Psychiatric Symptoms and Health-Related Quality of Life.

Patient-initiated brief admission (PIBA) was developed for patients with emotional instability and self-harm, to cope with crises. The hypothesis was that psychiatric symptoms would decrease, and health-related quality of life (HRQoL) increase, after 1-3 days at hospital. One hundred and thirteen patients were recruited from a psychiatric clinic in Stockholm during 2016-2020. At admission and discharge, the patients completed the Hospital Anxiety and Depression Scale (HADS) and the EuroQoL-5 Dimension Questionnaire (EQ-5D). The patients also evaluated PIBA as a crisis intervention. A significant decrease in symptoms of anxiety and depression was found. HRQoL increased significantly assessed with EQ-5D and 95.2% of the participants found PIBA to be a constructive intervention.

Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia.

Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.

Effects of Patient-Initiated Brief Admissions on Psychiatric Care Consumption in Borderline Personality Disorder: ARegister-Based Study.

Previous studies have reported that patients with borderline personality disorder (BPD) often have negative experiences in psychiatric inpatient care. To address this issue, a novel intervention known as patient-initiated brief admission (PIBA) has been developed. PIBA offers a constructive approach to crisis management in situations of heightened anxiety, as well as during instances of self-harm and suicidal ideation. The intervention allows patients to directly contact the psychiatric ward to initiate a brief admission lasting 1-3 days. This easily accessible care option during a crisis has the potential to prevent harm to the patient and reduce the need for prolonged hospital stays. The aim of the present study is to investigate the effects of PIBA on psychiatric care consumption among patients diagnosed with BPD. This retrospective register-based study includes data from both inpatient and outpatient care registries for patients diagnosed with BPD. Data were extracted from the National Board of Health and Welfare in Sweden. The study period encompasses 2013-2020, with the PIBA intervention occurring between 2016 and 2019. The sample included 107 patients in the PIBA group and 5659 matched controls. Data were analysed using a difference-in-differences (DiD) approach through ordinary least squares (OLS) regression and ordinal logistic regression. Throughout the 3-year follow-up, both groups exhibited a reduction in the number of days of utilisation of psychiatric inpatient care services. The DiD analysis indicated an additional decrease of 1.5 days at the 6-month mark for the PIBA group (ß = -1.436, SE = 1.531), expanding to 3 days fewer at the 12-month follow-up (ß = -3.590, SE = 3.546), although not statistically significant. For outpatient care, the PIBA group displayed an increase in the number of visits, averaging to half a visit more every 6 months (ß = 0.503, SE = 0.263) compared with the controls. Statistically significant differences were observed for two out of six measurements at the 12-month (ß = 0.960, SE = 0.456) and 18-month follow-up period (ß = 0.436, SE = 0.219). The PIBA group had a statistically significant lower odds of experiencing extended lengths of inpatient care days after the index date than the controls (OR 0.56, 95% CI: 0.44-0.72). In conclusion, PIBA was associated with a significant reduction in the length of individual hospital stays, but not in the overall number of inpatient care days. PIBA may be linked to a shift from longer inpatient care utilisation to outpatient care utilisation. These findings suggest that PIBA may reduce the risk of prolonged hospitalisations for patients who have access to the intervention. Future research should explore the impact of PIBA on healthcare costs and cost-effectiveness, both in relation to health care for the individual and cost-effectiveness in relation to recovery and health.

What are the effects of implementing patient-controlled admissions in inpatient care? A study protocol of a large-scale implementation and naturalistic evaluation for adult and adolescent patients with severe psychiatric conditions throughout Region Stockholm.

INTRODUCTION: Patient-controlled admissions (PCAs) represent a change in psychiatric inpatient care where patients are allowed to decide for themselves when hospitalisation might be required. Prior research has demonstrated that PCA increase the number of admissions, but decrease days in inpatient care, while both the admissions to and days in involuntary care decrease. However, investigations have been restricted to specific patient groups and have not examined other possible benefits, such as effects on symptoms, quality of life and autonomy. METHODS AND ANALYSIS: This study explores the implementation process and effects of PCA in Region Stockholm, who is currently introducing PCA for all patients with severe psychiatric conditions and extensive healthcare utilisation. In total, the study comprises approximately 45 inpatient wards, including child and adolescent psychiatry. In a naturalistic evaluation, patients assigned PCA will be followed up to 36 months, both with regard to hospitalisation rates and self-reported outcomes. In addition, qualitative studies will explore the experiences of patients, caregivers of adolescents and healthcare providers. ETHICS AND DISSEMINATION: Approval has been granted by the Swedish Ethical Review Authority (Dnr: 2020-06498). The findings from this study will be disseminated via publications in international peer-reviewed journals, at scientific conferences, as part of two doctoral theses, and through the Swedish Partnership for Mental Health. TRIAL REGISTRATION NUMBER: NCT04862897.

No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis.

Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [11C]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (ß = 0.013-0.074, partial r = -0.037-0.273, p = 0.131-0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3-8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.

Plasma bilirubin levels are reduced in first-episode psychosis patients and associates to working memory and duration of untreated psychosis.

Schizophrenia is a severe mental disorder and one of its characteristics is cognitive impairments. Findings regarding levels of the heme metabolite and plasma antioxidant bilirubin in schizophrenia are inconclusive. However, a recently published study indicate that low levels of bilirubin may be implicated in the memory impairments seen in the disorder. The aim of this cross-sectional study was to investigate the levels of bilirubin in individuals with a first-episode psychosis (FEP) and to examine if bilirubin levels were associated to cognitive impairments, symptoms and duration of untreated psychosis (DUP). Bilirubin levels were reduced in 39 individuals with FEP compared with 20 HC (median [IQR]: 11.0 [9.0-13.0] µM vs. 15.0 [11.5-18.5] µM). In individuals with FEP, bilirubin levels were also positively correlated to two working memory tests (r = 0.40 and r = 0.32) and inversely correlated to DUP (r = - 0.36). Findings were not influenced by confounding factors. The results confirm the antioxidant deficit previously seen in schizophrenia, but also indicate that these changes may be related to DUP. The study also confirms that bilirubin may be implicated in the cognitive deficits that accompanies the disorder, here for the first time presented in individuals with FEP.

Undetected depression in primary healthcare: occurrence, severity and co-morbidity in a two-stage procedure of opportunistic screening.

BACKGROUND: Depression often remains undetected in primary healthcare, and a two-stage screening procedure has been recommended for future research on the recognition, management and outcome of these patients. The aim of this study was to analyse the occurrence and the severity of depression, as well as gender, age and psychiatric co-morbidity in patients with previously undetected depression using a screening questionnaire followed by a diagnostic interview for detecting depression among patients visiting primary healthcare. METHODS: All patients visiting a primary healthcare centre during a period of 10 days were asked to fill in the self-rating version of the Montgomery-Åsberg Depression Rating Scale. Patients with a score of 12 or more were invited to participate in a structured diagnostic interview based on the Primary Care Evaluation of Mental Disorders. RESULTS: Out of 221 (=N) participants, 45 (20.4%) patients showed signs of depression (scores of 12 or more). Of these 45 patients, 31 consented to the structured interview, and of those, 28 (12.7%) fulfilled the criteria for depression, 17 (7.7%) had a major depression and 11 (5.0%) had a mixed depression-anxiety condition. CONCLUSIONS: The rate of undetected depression in primary healthcare was considerable. The majority of these patients had a major depression. Psychiatric co-morbidity among depressed patients was almost universal. The two-stage procedure of opportunistic screening with the Montgomery-Åsberg Depression Rating Scale and the Primary Care Evaluation of Mental Disorders seems to be a feasible method for detecting these patients in primary healthcare.

Brief admission for patients with emotional instability and self-harm: A qualitative analysis of patients' experiences during crisis.

Previous studies report that individuals diagnosed with borderline personality disorder have been met by negative attitudes from healthcare professionals and their care needs have often been neglected during hospitalizations. When symptoms of emotional instability are combined with self-harm, the resulting crisis often becomes difficult to handle for patients and healthcare professionals. To meet their care needs during these crises, an intervention called 'brief admission' (BA) has been developed. The purpose of BA is to provide a timeout, in situations of increased stress and threat, in order to foster self-management in a safe environment. In the present study, we explored the following research questions: What are patients' experiences with BA? What do patients consider to be the key components of BA? What improvements are considered relevant by patients? A qualitative design was employed, and 15 patients (13 females, 2 males; mean age 38.5 ± 12.9, range 20-67 years) were interviewed using a semi-structured interview guide. Thematic analyses were performed, which yielded four themes related to the patients' experiences: 'a timeout when life is tough', 'it is comforting to know that help exists', 'encouraged to take personal responsibility', and 'it is helpful to see the problems from a different perspective'. Four themes also described the key components: 'a clear treatment plan', 'a smooth admission procedure', 'a friendly and welcoming approach from the staff', and 'daily conversations'. Lastly, three themes described areas for improvements: 'feeling guilty about seeking BA', 'room occupancy issues', and 'differences in staff's competence'. Collectively, the findings indicate that BA constructively supports patients with emotional instability and self-harm during a period of crisis.

Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts. METHODS: We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18-94 years of age) and applied the models to the test sets including 648 patients with SZ (18-66 years of age), 185 patients with BD (18-64 years of age), and 990 HC subjects (17-68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results. RESULTS: Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen's d = -0.29) and patients with BD (Cohen's d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy-based models showed larger group differences than the models based on other DTI-derived metrics. CONCLUSIONS: Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.

The genetic architecture of human brainstem structures and their involvement in common brain disorders.

Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.

Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Brief admission (BA) for patients with emotional instability and self-harm: nurses' perspectives - person-centred care in clinical practice.

Purpose: Emotional instability and self-harm pose major problems for society and health care. There are effective interventions in outpatient care, but when patients need inpatient care, nurses often struggle meeting their patient's needs. Brief admission (BA) is a newly implemented crisis intervention and novel form of inpatient care. The aim of this study is to describe nurses' experiences working with BA related to patients with emotional instability and self-harm. Methods: Eight nurses were interviewed according to a semi-structured interview guide. The data was analysed using qualitative content analysis. Results: Four main categories emerged regarding nurses' experiences with BA: provides security and continuity, fosters caring relationships, shifts focus towards patient's health and empowers the patient. The nurse's role shifted from "handling problems" to establishing caring relationships with a focus on the person's health and possibilities for recovering instead of psychiatric symptoms. Conclusions: Previous studies on patients' perspective of BA describe positive experiences such as increased autonomy and participation in the healthcare process. This study supports those findings, albeit from the perspective of nurses. Our findings suggest that BA may reduce work-related stress experienced by nurses while caring for persons with emotional instability and self-harm. BA may also support nurses in their ability to provide more meaningful and constructive psychiatric inpatient care.

[New national guidelines for the treatment of schizophrenia in Sweden]. / Nya nationella riktlinjer för vård och stöd vid schizofreni - Lyfter fram ¼återhämtningsperspektivet«: Rehabilitering i kombination med läkemedel kan ge bättre livskvalitet.

Schizophrenia affects about 0.7 % of the population and is characterized by hallucinations, delusions and reduced functioning affecting the ability to study, work and socialize. Life expectancy for patients with schizophrenia is approximately 15-20 years shorter mostly due to cardiovascular disease. Stigmatization is  common despite the fact that it is a treatable disorder with a combination of medication and psychosocial interventions. Case management, psycho-education and supported employment are proven strategies, but less than half of individuals with schizophrenia are adequately treated. The National Board of Health and Welfare is currently launching updated National Guidelines (2018). The aim is to provide an overview of evidence-based interventions enabling patients with schizophrenia to live a fairly normal life. An evaluation has revealed that previous guidelines for antipsychotic medications have been satisfactorily implemented, but not those for psychosocial interventions. These will now be emphasized as ¼central recommendations« and will be followed up with specific indicators based on data from national registers.

Effect of Brief Admission to Hospital by Self-referral for Individuals Who Self-harm and Are at Risk of Suicide: A Randomized Clinical Trial.

Importance: To our knowledge, there is no consensus regarding when individuals who repeatedly self-harm and are at risk of suicide should be hospitalized. To evaluate a new alternative, we examined the effects of brief admission (BA) to hospital by self-referral. Objectives: To determine the effects of BA on inpatient service use and on secondary outcomes of daily life functioning, nonsuicidal self-injuries, and attempted suicide among individuals who self-harm and are at risk of suicide. Design, Setting, and Participants: The single-masked Brief Admission Skåne Randomized Clinical Trial was conducted from September 2015 to June 2018 at 4 psychiatric health care facilities in southern Sweden. Data were collected 6 months retrospectively at baseline and at 6-month and 12-month follow-ups. Participants were randomized to either BA and treatment as usual (BA group) or treatment as usual (control group). The sample was a referral population, with the most important inclusion criteria being current episodes of self-harm and/or recurrent suicidality, at least 3 diagnostic criteria for borderline personality disorder, and hospitalization in the last 6 months. Interventions: Self-referred BA was offered for 12 months, with standard limits for duration and frequency, after the negotiation of a contract outlining the intervention. Main Outcomes and Measures: Prespecified main outcome measures were days admitted to the hospital, including voluntary admission, BA, and compulsory admission. Results: The 125 participants had a mean (SD) age of 32.0 (9.4) years, 106 (84.8%) were women, and 63 were randomized to the BA group and 62 to the control group. No significant advantage was observed in the number of days in the hospital for the BA group compared with the control group. Within-group analyses demonstrated significant decreases in both groups regarding days admitted to the hospital (BA group: χ2 = 22.71; P < .001; control group: χ2 = 23.01; P < .001) and visits to the emergency department (BA group: χ2 = 13.95; P < .001; control group: χ2 = 21.61; P < .001), but only the BA group showed a reduction in days with compulsory admission (χ2 = 7.67; P = .02) and nonsuicidal self-injuries (χ2 = 6.13; P = .047). The BA group showed significantly greater improvements in the mobility domain of daily life functioning (z = -2.39; P = .02) and significant within-group improvements in 3 other domains (cognition: F = 9.02; P < .001; domestic responsibilities: F = 3.23; P = .049; and participation: F = 3.79; P = .03). Conclusions and Relevance: Brief admission appears no more efficacious in reducing use of inpatient services than usual care for individuals who self-harm and are at risk of suicide. Future studies should explore other possible beneficial effects. Trial Registration: ClinicalTrials.gov identifier: NCT02985047.

Increased peripheral levels of TARC/CCL17 in first episode psychosis patients.

BACKGROUND: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drug-naïve or short-time medicated first episode psychosis (FEP) patients. METHOD: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. RESULTS: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in >50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. CONCLUSION: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exact mechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest.

Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk.

Importance: Between-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. Objectives: To compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and Participants: This case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and Measures: Mean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. Results: A comparison of 1151 patients with schizophrenia (mean [SD] age, 33.8 [10.6] years; 68.6% male [n = 790] and 31.4% female [n = 361]) with 2010 healthy controls (mean [SD] age, 32.6 [10.4] years; 56.0% male [n = 1126] and 44.0% female [n = 884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t = 3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age, 55.9 [7.5] years; 48.2% male [n = 6025] and 51.8% female [n = 6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t = -3.00) but was not significantly associated with dispersion. Conclusions and Relevance: This study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.