Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Mental health recovery and physical health outcomes in psychotic illness: Longitudinal data from the Western Australian survey of high impact psychosis catchments.

OBJECTIVE: There is a dearth of longitudinal data on outcomes in prevalent cases of psychotic illness across a range of ages and levels of chronicity. Our aim was to describe changes over time in mental and physical health outcomes, as well as patterns of service utilisation that may have influenced outcomes, in a representative prevalence sample of 641 Western Australians with a psychotic illness who, at Wave 1, were part of the National Survey of High Impact Psychosis. METHODS: In Wave 1 (2010, 2012), a two-phase design was employed to ensure representativeness: Phase 1 psychosis screening took place in public mental health and non-government organisation services, while, in Phase 2, a randomised sample was interviewed. In Wave 2, 380/641 (59%) of participants were re-interviewed, with interviews staggered between 2013 and 2016 (follow-up time: 2.3-5.6 years). Data collection covered mental and physical health, functioning, cognition, social circumstances and service utilisation. Mental health outcomes were categorised as symptomatic, functional and personal recovery. Physical health outcomes covered metabolic syndrome and its component criteria. RESULTS: In mental health, there were encouraging improvements in symptom profiles, variable change in functional recovery and some positive findings for personal recovery, but not quality of life. Participants ranked physical health second among challenges. Metabolic syndrome had increased significantly. While treatment for underlying cardiovascular risk conditions had improved, rates of intervention were still very low. More people were accessing general practices and more frequently, but there were sharp and significant declines in access to community rehabilitation, psychosocial interventions and case management. CONCLUSION: Although we observed some positive outcomes over time, the sharp decline in access to evidence-based interventions such as community rehabilitation, psychosocial interventions and case management is of great concern and augurs poorly for recovery-oriented practice. Changes in service utilisation appear to have influenced the patterns found.

A comparison of trajectories of offending among people with psychotic disorders, other mental disorders and no mental disorders: Evidence from a whole-of-population birth cohort study.

BACKGROUND: Trajectory analysis has been used to study long-term offending patterns and identify offender subgroups, but few such studies have included people with psychotic disorders (PDs) and these have been restricted to adult offenders. AIMS: To compare offending trajectories among 10-26-year-olds with PDs with those with other mental disorders (OMDs) or none (NMD) and identify associated risk factors. METHODS: This is a record-linkage study of 184,147 people born in Western Australia (WA) 1983-1991, drawing on data from WA mental health information system, WA corrective services and other state-wide registers. Group-based trajectory modelling was used to identify offending trajectories. RESULTS: Four offender groups were identified in each mental health status group: G1-no/negligible offending; G2-early onset, adolescent, desisting by age 18; G3-early onset, low rate, offending into early adulthood; and G4-very early onset, high rate, peaking at age 17, continuing into early adulthood. The PDs group had the lowest proportion of individuals with no or negligible offending histories-84% compared with 88.5% in the OMDs group and 96.6% in the no mental disorder group. Within mental health status offender groups, the PDs group was characterised by early or very early onset offending persisting into adulthood, accounting for 5.4% and 3.7% of the group respectively (OMD: 3.8%, 1.5%; NMD: 1.0%, 0.5%). Gender, indigenous status, substance use problems, childhood abuse and parental offending were generally associated with trajectory group membership, although among those with PDs childhood abuse and parental offending were only significant in the early onset-life-course-persistent group. CONCLUSIONS: While most people with PDs never offend, some are disproportionately vulnerable from a particularly early age. If the offending subgroup is to be helped away from criminal justice involvement, interventions must be considered in childhood.

Rediscovering the value of families for psychiatric genetics research.

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.5% or less, very large samples of unrelated individuals are necessary to unambiguously associate a locus with an illness. Unfortunately, such large samples are often cost prohibitive. However, by using alternative analytic strategies and studying related individuals, particularly those from large multiplex families, it is possible to reduce the required sample size while maintaining statistical power. We contend that using whole genome sequence (WGS) in extended pedigrees provides a cost-effective strategy for psychiatric gene mapping that complements common variant approaches and WGS in unrelated individuals. This was our impetus for forming the "Pedigree-Based Whole Genome Sequencing of Affective and Psychotic Disorders" consortium. In this review, we provide a rationale for the use of WGS with pedigrees in modern psychiatric genetics research. We begin with a focused review of the current literature, followed by a short history of family-based research in psychiatry. Next, we describe several advantages of pedigrees for WGS research, including power estimates, methods for studying the environment, and endophenotypes. We conclude with a brief description of our consortium and its goals.

Wnt receptor gene FZD1 was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort.

OBJECTIVES: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories. METHODS: We performed a case-control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome. RESULTS: The strongest finding (p = 2.01 × 10-6, odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance (p = 2.78 × 10-6). CONCLUSION: The identification of FZD1, as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development.

Impact of substance use and other risk factor exposures on conviction rates by people with a psychotic illness and other mental disorders.

PURPOSE: To examine the impact of substance use and other risk factors on conviction rates in people with a psychotic illness (PI) and other mental disorders (OMD) compared to those with no mental illness (NMI). METHODS: This research is part of a longitudinal record-linked whole-population study of 467,945 children born in Western Australia (WA) between 1980 and 2001. This cohort was identified through linkages between the WA psychiatric case register, WA corrective services data and other state-wide registers. We assessed 184,147 individuals born during 1983-1991 to explore the impact of exposure to a variety of risk factors on conviction rates. RESULTS: People with PI and OMD had higher conviction rates than those with NMI, with unadjusted incidence rate ratios (IRR) of 3.98 (95% CI 3.67-4.32) for PI and 3.18 (95% CI 3.03-3.34) for OMD. Adjusting for substance use reduced the rates by 60% in PI and 30% in OMD: IRRs 1.59 (95% CI 1.45-1.74) and 2.24 (2.12-2.37), respectively. Minimal change was seen when adjusting for other potential risk factors (including socio-demographics, victimisation and parental offending), with adjusted IRRs 1.58 (95% CI 1.43-1.74) for PI and 1.90 (95% CI 1.80-2.02) for OMD. CONCLUSIONS: Our analysis shows people with a mental illness have higher rates of conviction than those with NMI. Substance use has a major impact on this rate. Results suggest the need for a greater investment in programs addressing the issue of comorbid substance use with a view to reduce the rate of convictions in this population.

Use of the Communication Checklist - Self Report (Cc-Sr) in Schizophrenia: Language Impairments Correlate with Poor Premorbid Social Adjustment.

BACKGROUND: The present study reports preliminary results from the multicentre project on the approbation of the Russian language version of the "The Communication Checklist-Self Report" (RL-CC-SR) and its first use in schizophrenia (SZ), aiming to evaluate the contribution of language disturbances in the pathogenesis of this heterogeneous disorder. SUBJECTS AND METHODS: The study evaluated patients' clinical state with the Diagnostic Interview for Psychoses (DIP), and assessed language and communication disturbances (LCD) with the RL-CC-SR in all participants (213 healthy controls (HC), 83 SZ patients, 31 SZ first-degree relatives). Data from the current sample of SZ (n=50), and HC (n=213) was analysed to calculate the relationships between LCD, social and clinical variables using descriptive statistics methods, T-test and Pearson's correlations (SPSS-26, 2019). RESULTS: The quotient scores (<6) and raw scores on all three CC-SR subscales demonstrated prominent LCD in SZ: (i) language structure (LS) (SZ:11.92±8.01, HC:7.54±5.91; p<0.001), (ii) pragmatic skills (PS) (SZ:11.30±10.07, HC:8.71±7.39; p=0.040), (iii) social engagement (SE) (SZ:31.94±11.76, HC:19.42±10.35; p<0.001). In SZ, Pearson correlations of LS scores were significant for the DIP-items Odd Speech (p=0.033), and Social Engagement - Blunted Affect (p=0.042). PS was related to early disease onset (p=0.027), poor premorbid work adjustment (p=0.003), along with LS (p=0.005), and was also linked to poor premorbid social adjustment (p=0.005). CONCLUSIONS: SZ patients are aware of their LCD at all levels of language structure, pragmatics, and nonverbal communication, but are unable to compensate. Disturbances of LS and PS in SZ patients relate to their poor social adjustment and functioning, and may prove to be associated with the primary negative symptoms domain of the disorder and its generally poor outcome.

Are familial liability for schizophrenia and obstetric complications independently associated with risk of psychotic illness, after adjusting for other environmental stressors in childhood?

OBJECTIVE: The interplay between genetic and environmental factors on risk for psychotic illness remains poorly understood. The aim of this study was to estimate independent and combined effects of familial liability for schizophrenia and exposure to obstetric complications on risk for developing psychotic illness, covarying with exposure to other environmental stressors. METHODS: This whole-population birth cohort study used record linkage across Western Australian statewide data collections (midwives, psychiatric, hospital admissions, child protection, mortality) to identify liveborn offspring (n = 1046) born 1980-1995 to mothers with schizophrenia, comparing them to offspring of mothers with no recorded psychiatric history (n = 298,370). RESULTS: Both maternal schizophrenia and pregnancy complications were each significantly associated with psychotic illness in offspring, with no interaction. Non-obstetric environmental stressors significantly associated with psychotic illness in offspring included the following: being Indigenous; having a mother who was not in a partnered relationship; episodes of disrupted parenting due to hospitalisation of mother, father or child; abuse in childhood; and living in areas of greatest socioeconomic disadvantage and with elevated rates of violent crime. Adjustment for these other environmental stressors reduced the hazard ratio for maternal schizophrenia substantially (from hazard ratio: 5.7, confidence interval: 4.5-7.2 to hazard ratio: 3.5, confidence interval: 2.8-4.4), but not the estimate for pregnancy complications (hazard ratio: 1.1, confidence interval: 1.0-1.2). The population attributable fraction for maternal schizophrenia was 1.4 and for pregnancy complications was 2.1. CONCLUSION: Our finding of a substantial decrease in risk of psychotic illness associated with familial liability for psychosis following adjustment for other environmental stressors highlights potentially modifiable risk factors on the trajectory to psychotic illness and suggests that interventions that reduce or manage exposure to these risks may be protective, despite a genetic liability.

Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders.

BACKGROUND: There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.AimsTo investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls. METHOD: Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls. RESULTS: Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest. CONCLUSIONS: Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.Declaration of interestR.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.

A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains.

This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the Ray Auditory Verbal Learning Task (N = 2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p = 0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p = 0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p = 0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.

The 2016 Royal Australian and New Zealand College of Psychiatrists guidelines for the management of schizophrenia and related disorders.

INTRODUCTION: The Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines for the management of schizophrenia and related disorders provide evidence-based recommendations for optimising treatment and prognosis. This update to the 2005 RANZCP guidelines has a greater emphasis on psychosocial treatments, physical health comorbidities and vocational rehabilitation. Main recommendations: The guidelines advise a clinical staging approach and deliver specific recommendations for:•comprehensive treatment using second generation antipsychotic agents continuously for 2-5 years;•early treatment of comorbid substance use;•community treatment after initial contact, during crises and after discharge from hospital;•physical health monitoring and management of comorbidities, particularly metabolic health;•interventions to optimise recovery of social function and return to study or work; and•management of schizophrenia in specific populations and circumstances. Changes in management as a result of the guidelines: The guidelines provide benchmarks against which the performance of services and clinical teams can be assessed. Measuring treatment response and clinical outcome is essential. General practitioners have an important role, particularly in monitoring and reducing the high cardiovascular risk in this population. Clinical services focusing on early detection, treatment and recovery need continuous funding to be proactive in implementing the guidelines and closing the gap between what is possible and what actually occurs.

Impact of social disadvantage and parental offending on rates of criminal offending among offspring of women with severe mental illness.

OBJECTIVE: Children of parents with severe mental illness have an increased risk of offending. Studies suggest that risk factors such as parental offending and social disadvantage may be associated with the increased risk. This paper assesses the impact of these risk factors on offending rates in the offspring of women with severe mental illness compared to offspring of unaffected women. METHODS: This is part of a longitudinal record-linked whole-population study of 467,945 children born in Western Australia from 1980 to 2001 to mothers with severe mental illness and mothers with no recorded psychiatric illness. These data were linked to Western Australia corrective services data producing a dataset of 12,999 people with at least one offence (3.7% of birth cohort). Cox proportional hazard was used to calculate incidence rate ratios of offspring offending. RESULTS: The offending rate for offspring of mothers with severe mental illness (cases) was almost three times the rate for offspring of unaffected mothers (comparison) with an unadjusted incidence rate ratio of 2.75 (95% confidence interval: [2.58, 2.93]). Adjusting for sex, indigenous status, socio-economic status and geographical remoteness reduced the rate ratio by 24% to incidence rate ratio 2.10, 95% confidence interval: [1.97, 2.23]. Adjusting for parental offending further reduced the rate ratio by 23% to incidence rate ratio 1.62, 95% confidence interval: [1.52, 1.72]. The mean age at first recorded offence was significantly lower for cases compared to comparison offspring. CONCLUSION: Children of mothers with a severe mental illness have a higher rate of offending than children of unaffected mothers, and social disadvantage and parental offending have a major impact on this rate. Services supporting these vulnerable children need to focus on improving the social environment in which they and their families live in.

Responding to challenges for people with psychotic illness: Updated evidence from the Survey of High Impact Psychosis.

OBJECTIVE: The objective is to summarise recent findings from the 2010 Australian Survey of High Impact Psychosis (SHIP) and examine their implications for future policy and planning to improve mental health, physical health and other circumstances of people with a psychotic disorder. METHODS: Survey of High Impact Psychosis collected nationally representative data on 1825 people with psychotic illness. Over 60 papers have been published covering key challenges reported by participants: financial problems, loneliness and social isolation, unemployment, poor physical health, uncontrolled symptoms of mental illness, and lack of stable, suitable housing. Findings are summarised under the rubric of participant-ranked top challenges. RESULTS: The main income source for the majority (85%) of participants was a government benefit. Only one-third was employed, and the most appropriate employment services for this group were under-utilised. High rates of loneliness and social isolation impacted mental and physical health. The rate of cardiometabolic disease was well above the general population rate, and associated risk factors were present from a very young age. Childhood abuse (30.6%), adult violent victimisation (16.4%) and alcohol and substance abuse/dependence (lifetime rates of 50.5% and 54.5%, respectively) complicated the clinical profile. Treatment with medication was suboptimal, with physical health conditions undertreated, a high rate of psychotropic polypharmacy and underutilisation of clozapine in chronic persistent psychotic illness. Only 38.6% received evidence-based psychosocial therapies. In the previous year, 27.4% had changed housing and 12.8% had been homeless, on average for 155 days. CONCLUSION: Money, social engagement and employment are the most important challenges for people with psychotic illness, as well as good physical and mental health. An integrated approach to recovery is needed to optimise service delivery and augment evidence-based clinical practice with measures to improve physical health and social circumstances. Meeting these challenges has the potential to reduce costs to government and society, as well as promote recovery.

The 2016 RANZCP Guidelines for the Management of Schizophrenia and Related Disorders - what's next?

OBJECTIVES: The recently published RANZCP guidelines for schizophrenia and related disorders reviewed recent scientific evidence, and, where lacking, referred to clinical expertise to supply a template for raising the standard of care. This paper builds on the guidelines and recommends how they might be used to improve outcomes. METHODS: The guidelines call for evidence-based mental health policies, inclusive of mobilising affected families, communities and the public in support of policies that ensure better care and protect the wellbeing of people with severe mental disorders. The process of preparing the guidelines highlighted the limits of our scientific understanding of schizophrenia and shortcomings in the care currently provided. RESULTS: Writing the guidelines evinced the need for a culture of measuring outcomes and response to treatment, and harnessing such data to monitoring and optimising patient care. CONCLUSIONS: We recommend creation of a national case cohort for mental health research involving a collaborative network of clinical research centres, using the guidelines and generating scientific evidence for translation into clinical practice protocols that enable personalised treatment plans for patients and criteria for the performance of clinical services.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders.

OBJECTIVES: This guideline provides recommendations for the clinical management of schizophrenia and related disorders for health professionals working in Australia and New Zealand. It aims to encourage all clinicians to adopt best practice principles. The recommendations represent the consensus of a group of Australian and New Zealand experts in the management of schizophrenia and related disorders. This guideline includes the management of ultra-high risk syndromes, first-episode psychoses and prolonged psychoses, including psychoses associated with substance use. It takes a holistic approach, addressing all aspects of the care of people with schizophrenia and related disorders, not only correct diagnosis and symptom relief but also optimal recovery of social function. METHODS: The writing group planned the scope and individual members drafted sections according to their area of interest and expertise, with reference to existing systematic reviews and informal literature reviews undertaken for this guideline. In addition, experts in specific areas contributed to the relevant sections. All members of the writing group reviewed the entire document. The writing group also considered relevant international clinical practice guidelines. Evidence-based recommendations were formulated when the writing group judged that there was sufficient evidence on a topic. Where evidence was weak or lacking, consensus-based recommendations were formulated. Consensus-based recommendations are based on the consensus of a group of experts in the field and are informed by their agreement as a group, according to their collective clinical and research knowledge and experience. Key considerations were selected and reviewed by the writing group. To encourage wide community participation, the Royal Australian and New Zealand College of Psychiatrists invited review by its committees and members, an expert advisory committee and key stakeholders including professional bodies and special interest groups. RESULTS: The clinical practice guideline for the management of schizophrenia and related disorders reflects an increasing emphasis on early intervention, physical health, psychosocial treatments, cultural considerations and improving vocational outcomes. The guideline uses a clinical staging model as a framework for recommendations regarding assessment, treatment and ongoing care. This guideline also refers its readers to selected published guidelines or statements directly relevant to Australian and New Zealand practice. CONCLUSIONS: This clinical practice guideline for the management of schizophrenia and related disorders aims to improve care for people with these disorders living in Australia and New Zealand. It advocates a respectful, collaborative approach; optimal evidence-based treatment; and consideration of the specific needs of those in adverse circumstances or facing additional challenges.

Sociodemographic, clinical and childhood correlates of adult violent victimisation in a large, national survey sample of people with psychotic disorders.

PURPOSE: Our aim was to establish the 12-month prevalence of violent victimisation in a large sample of adults with psychotic disorders (N = 1825), compare this to population estimates, and examine correlates of violent victimisation. METHODS: The Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders. Interview questions included psychopathology, cognition, sociodemographics, substance use, criminality, and childhood and adult victimisation. Multivariable logistic regression models were used to examine the independent contributions of known risk factors, clinical profile and childhood abuse, on risk of violent victimisation. Differences between men and women were examined. RESULTS: Among adults with psychotic disorders, 12-month prevalence of any victimisation was 38.6% (males 37.4%, females 40.5%), and of violent victimisation was 16.4% (males 15.2%; females 18.3%). Violent victimisation was 4.8 times higher than the population rate of 3.4% (6.5 times higher for women; 3.7 times higher for men). Significant correlates of violent victimisation were established sociodemographic and behavioural risk factors predicting victimisation in the general community: younger age, residence in the most disadvantaged neighbourhoods, homelessness, lifetime alcohol abuse/dependence, and prior criminal offending. Among clinical variables, only mania and self-harm remained significant in the multivariable model. Childhood abuse was independently associated with violent victimisation. CONCLUSIONS: Rates of violent victimisation are high for people with psychotic disorders, especially women, compared to population rates. Greater exposure to sociodemographic and behavioural risks may render them particularly vulnerable to victimisation. Social cognition as a valuable treatment target is discussed.

Cortical similarities in psychiatric and mood disorders identified in federated VBM analysis via COINSTAC.

Structural neuroimaging studies have identified a combination of shared and disorder-specific patterns of gray matter (GM) deficits across psychiatric disorders. Pooling large data allows for examination of a possible common neuroanatomical basis that may identify a certain vulnerability for mental illness. Large-scale collaborative research is already facilitated by data repositories, institutionally supported databases, and data archives. However, these data-sharing methodologies can suffer from significant barriers. Federated approaches augment these approaches by enabling access or more sophisticated, shareable and scaled-up analyses of large-scale data. We examined GM alterations using Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation, an open-source, decentralized analysis application. Through federated analysis of eight sites, we identified significant overlap in the GM patterns (n = 4,102) of individuals with schizophrenia, major depressive disorder, and autism spectrum disorder. These results show cortical and subcortical regions that may indicate a shared vulnerability to psychiatric disorders.

Does accumulating exposure to illicit drugs bring forward the age at onset in schizophrenia?

OBJECTIVE: Whilst cannabis has been associated with an earlier age at onset in schizophrenia, the impact of amphetamine and/or cocaine plus cannabis consumption on age at onset remains unclear. The present study was designed to test the hypothesis that consumption of amphetamine and/or cocaine in addition to cannabis would lead to an earlier age at onset of schizophrenia than that seen for cannabis consumption alone. A secondary objective was to determine what kind of effect additional substance use exerted (e.g. additive, multiplicative). METHOD: Patients with a diagnosis of schizophrenia were recruited from consecutive admissions to the inpatient and outpatient services of a large psychiatric hospital in Perth, Australia and 167 participants were assessed using the Diagnostic Interview for Psychosis, which included detailed inquiry into illicit drug use in the 12 months prior to the onset of psychiatric symptoms. Participants were categorized into four groups: no illicit substance use (n = 65), cannabis use (n = 68), cannabis plus amphetamine use (n = 25), and cocaine plus cannabis/cocaine plus cannabis plus amphetamine use (n = 9). Analysis of variance was performed to detect trends, and linear regression used to analyze the consumption of each additional substance as a predictor of age at onset. RESULTS: We observed a linear trend for mean age at onset: 23.34 (SD = 6.91) years for no illicit substance use, 22.51 (SD = 5.27) years for cannabis use, 20.84 (SD = 3.48) years for cannabis plus amphetamine use, and 19.56 (SD = 3.54) years for cocaine plus cannabis/cocaine plus cannabis plus amphetamine use; the variation in the means between groups was statistically significant: F(1,163) = 5.66, p = 0.008, Cohen's d = 0.38. For the consumption of each additional substance, age at onset was earlier by 1.2 years: R (2) = 0.034, F(1,165) = 5.72, p = 0.018. CONCLUSIONS: Whilst preliminary, these findings suggest that additional consumption of each substance predicted an earlier age at onset by approximately 1 additional year.

Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression.

BACKGROUND: Recent evidence points to partially shared genetics of neuropsychiatric disorders. AIMS: We examined risk of intellectual disability and other neuropsychiatric outcomes in 3174 children of mothers with schizophrenia, bipolar disorder or unipolar major depression compared with 3129 children of unaffected mothers. METHOD: We used record linkage across Western Australian population-based registers. The contribution of obstetric factors to risk of intellectual disability was assessed. RESULTS: Children were at significantly increased risk of intellectual disability with odds ratios (ORs) of 3.2 (95% CI 1.8-5.7), 3.1 (95% CI 1.9-4.9) and 2.9 (95% CI 1.8-4.7) in the maternal schizophrenia, bipolar disorder and unipolar depression groups respectively. Multivariate analysis suggests familial and obstetric factors may contribute independently to the risk. Although summated labour/delivery complications (OR = 1.4, 95% CI 1.0-2.0) just failed to reach significance, neonatal encephalopathy (OR = 7.7, 95% CI 3.0-20.2) and fetal distress (OR = 1.8, 95% CI 1.1-2.7) were independent significant predictors. Rates of rare syndromes in children of mothers with mental disorder were well above population rates. Risk of pervasive developmental disorders, including autism, was significantly elevated for children of mothers with bipolar disorder. Risk of epilepsy was doubled for children of mothers with unipolar depression. CONCLUSIONS: Our findings provide epidemiological support for clustering of neuropsychiatric disorders. Further larger epidemiological studies are warranted.