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MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness., This review discusses the major challenges facing neuroimaging research of bipolar disorder and highlights the major accomplishments, ongoing challenges and future goals of the ENIGMA Bipolar Disorder Working Group.

Limited empirical evidence is available regarding the uptake and effectiveness of school-based mental health and wellbeing programs implemented in Australian schools. This study aimed to characterise the delivery of programs in primary (elementary) schools across New South Wales, Australia, and to assess this information against published ratings of program effectiveness. Delivery of programs in four health-promoting domains—creating a positive school community; teaching social and emotional skills; engaging the parent community; and supporting students experiencing mental health difficulties—were reported by 597 school principals/leaders via online survey. Although three quarters of principals reported implementing at least one program, many of these programs were supported by little or no evidence of effectiveness. There was also variability in the use of evidence-based programs across the four domains. Findings indicate a need to provide educators with improved support to identify, implement, and evaluate effective evidenced-based programs that promote student mental health.

There is known to be considerable overlap among the victims and perpetrators of crime. However, the extent of this overlap early in life among children and young adolescents is not clear. We examined the sociodemographic profiles of young people who had early contact with police regarding a criminal incident as a person of interest, victim and/or witness, as well as the patterns of multiple police contact types from birth to 13 years of age. Data were drawn from a longitudinal, population-based sample of 91,631 young people from New South Wales, Australia. Among the 10.6% (n = 9677) of young people who had contact with police, 14.4% (n = 1393) had contact as a person of interest and as a victim and/or witness on two or more separate occasions. The most common first contact type was as a victim/witness, but those children with a first contact as a person of interest were most likely to have at least one further contact. Young people with both types of police contact were younger at first police contact, were more likely to reside in a socioeconomically disadvantaged area, and to be recorded as having an Aboriginal and/or Torres Strait Islander background. Our findings demonstrate that, by 13 years of age, 1 in 10 young people had been in early contact with police and that a minority have contact with the police as both a person of interest and a victim/witness. These young people may represent a particularly disadvantaged group in the community who are likely to be at risk of future adversity, including repeated contact with the criminal justice system.

Children with disabilities are known to have high rates of contact with child protection services. However, little is known about child protection contacts for a broader group of children with special healthcare needs (SHCN; i.e., special needs or other impairments of concern that affect learning). This study examined the characteristics of contact with child protection services (prior to the age of 6 years) for children with SHCN identified at school entry using the 2009 Australian Early Development Census, using administrative data from more than 65,000 children in the New South Wales Child Development Study. Child protection contacts prior to age 6 years were more prevalent among children with SHCN compared with those without; in particular, children with SHCN had higher odds of a history of exposure to neglect and physical abuse, and higher odds of being placed in out-of-home care, compared with their typically developing peers. Understanding the characteristics of child protection contacts among children with SHCN, with consideration of factors that may influence their patterns of contact with these and other human services agencies, will inform the development of appropriate social policy initiatives to fulfil Australia’s obligations under the United Nations Convention on the Rights of the Child.

Adult psychosocial difficulties, including psychiatric disorders, are often preceded by childhood psychosocial vulnerabilities, presenting critical windows of opportunity for preventative intervention. The present study aimed to identify longitudinal patterns (representing transitions between profiles) of childhood socio-emotional and cognitive vulnerability in the general population from early to middle childhood, in relation to key risk factors (e.g. parental mental illness and offending). Data were drawn from the New South Wales Child Development Study, which combines intergenerational multi-agency administrative records with cross-sectional assessments using data linkage methods. We analysed data from childhood assessments of socio-emotional and cognitive functioning at two time points (ages 5-6 and 10-11 years) that were linked with administrative data from government departments of health, child protection, and education for 19,087 children and their parents. Latent profile analyses were used to identify socio-emotional and cognitive profiles at each time point, and latent transition analyses were used to determine the probability and potential moderators of transition between profiles at each age. Three developmental profiles were identified in early childhood, reflecting typically developing, emotionally vulnerable, and cognitively vulnerable children, respectively; two profiles were identified in middle childhood, reflecting typically developing and vulnerable children. Child's sex, child protection services contact, parental mental illness, and parental offending influenced children's transitions between different vulnerability profiles, with the strongest effects for parental mental illness and child protection contact. Early detection of vulnerable children and factors promoting resilience are important steps in directing future health and social policy, and service planning for vulnerable children.

Contact with the police, as the first contact with the criminal justice system for young people and children, may signify individuals who are vulnerable to later adverse social and health outcomes. However, little is known about how often children have contact with police or for what reason. In this paper, we provide a demographic profile of the prevalence and reasons for police contact among a representative, longitudinal, population-based sample of 91,631 young people in New South Wales, Australia. By 13 years of age, almost one in six (15.6%) children had contact with police as a victim, person of interest and/or witness on at least one occasion. The most common reason for contact with police was in relation to an assault. There was considerable overlap among children who had been in contact with police on more than one occasion for different reasons, with those having police contact as a person of interest or witness being seven times more likely to have also been in contact with police as a victim in a separate incident, than children not known to police. We show that contact with the police is surprisingly common among children and suggest that early interventions for children in contact with police might prevent a range of adverse outcomes not limited to criminal offending.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = −0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = −0.690, pspin = 0.006), BD (rho = −0.672, pspin = 0.009), and MDD (rho = −0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

The processes facilitating resilience are likely to be influenced by individual, familial and contextual factors that are dynamic across the life-course. These factors have been less studied in relation to resilience profiles evident in the developmental period between early to middle childhood, relative to later periods of adolescence or adulthood.This study examined factors associated withFactors associated with resilience profiles included being female, and personality characteristics of openness and extraversion; other factors associated withResilience processes appear to involve a complex interplay between individual, family, and community characteristics requiring interagency support.

Objectives Risk for psychosis in the general population is characterized by a set of multidimensional traits that are referred to as schizotypy. Higher levels of schizotypy are associated with socioeconomic disadvantage and childhood trauma, just as these risk factors are associated with schizophrenia and bipolar disorder. Here, we set out to investigate whether cumulative sociodemographic disadvantage mediates associations between childhood trauma and schizotypy in adulthood. Methods A sociodemographic cumulative risk (SDCR) score was derived from six risk indices spanning employment, education, income, socioeconomic status, marital, and living circumstances for 197 participants that included both healthy (n = 57) and clinical samples with schizophrenia or schizoaffective disorder (n = 65) or bipolar disorder (n = 75). A series of multiple linear regressions was used to examine the direct and indirect associations among childhood trauma (measured with the Childhood Trauma Questionnaire), the SDCR index, and levels of schizotypy (measured with the Schizotypal Personality Questionnaire). Results Schizotypy was independently associated with trauma and the SDCR index. In addition, the SDCR index partially mediated associations between trauma and schizotypy. Conclusions These findings in a mixed sample of healthy and clinical participants represent the full spectrum of schizotypy across health and illness and suggest that effects of childhood trauma on schizotypal personality organization may operate via cumulative socioeconomic disadvantage in adulthood. Practitioner points The strong associations between trauma and schizotypy suggest that systematic health screening of children exposed to early life trauma may assist to identify those at risk of developing psychosis. Clinicians should pay attention to various indicators of sociodemographic disadvantage in patients prone to psychosis, in addition to any exposure to trauma during childhood.

The delineation of cognitive subtypes of schizophrenia and bipolar disorder may offer a means of determining shared genetic markers and neuropathology among individuals with these conditions. We systematically reviewed the evidence from published studies reporting the use of data-driven (i.e., unsupervised) clustering methods to delineate cognitive subtypes among adults diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. We reviewed 24 studies in total, contributing data to 13 analyses of schizophrenia spectrum patients, 8 analyses of bipolar disorder, and 5 analyses of mixed samples of schizophrenia and bipolar disorder participants. Studies of bipolar disorder most consistently revealed a 3-cluster solution, comprising a subgroup with 'near-normal' (cognitively spared) cognition and two other subgroups demonstrating graded deficits across cognitive domains. In contrast, there was no clear consensus regarding the number of cognitive subtypes among studies of cognitive subtypes in schizophrenia, while four of the five studies of mixed diagnostic groups reported a 4-cluster solution. Common to all cluster solutions was a severe cognitive deficit subtype with cognitive impairments of moderate to large effect size relative to healthy controls. Our review highlights several key factors (e.g., symptom profile, sample size, statistical procedures, and cognitive domains examined) that may influence the results of data-driven clustering methods, and which were largely inconsistent across the studies reviewed. This synthesis of findings suggests caution should be exercised when interpreting the utility of particular cognitive subtypes for biological investigation, and demonstrates much heterogeneity among studies using unsupervised clustering approaches to cognitive subtyping within and across the psychosis spectrum.

Schizophrenia (SZ) and bipolar I disorder (BD) share common functional and structural brain abnormalities, as well as various degrees of social cognitive deficits, suggesting shared brain mechanisms. This study examined the relationship between social cognitive skills and structural brain integrity in 60 cases with SZ, 65 cases with psychotic BD, and 61 healthy controls (HCs). All participants underwent structural MRI and completed The Awareness of Social Inference Test (TASIT). Associations between social cognitive performance on each task of the TASIT (Emotion Recognition, Theory of Mind [ToM], and Complex ToM) and indices of gray matter volume and cortical thickness were investigated within three separate groups comprising (a) all cases with a history of psychosis (independently of their diagnostic status), (b) each diagnostic category separately, and (c) an HC group. Cases with psychosis showed worse social cognitive performance compared to the HC group, and SZ cases performed worse than BD on all ToM tasks, but not the Emotion Recognition subtest. Poor ToM performance was associated with thinner anterior temporal lobe in the combined group of cases with psychosis, and with decreased volume of the left fusiform gyrus/cerebellum in the HC group. In the BD group alone, poor ToM performance was associated with similar pattern of thinner anterior temporal lobe, as well as with increased volume in the mid- and posterior cingulate cortex/precuneus. However, there were no associations between brain morphometry and social cognition in the SZ group when considered alone. Taken together, ToM behavioral deficits were associated with thinner right anterior temporal lobe, a critical region from a larger affective ToM network among all cases with psychosis, but aberrant morphology of brain regions key for self-processing were specific to the BD group. These findings may have important implications for targeted interventions for the affective social brain network in BD.

Recent advances in human genomics have renewed interest in identifying the extent to which genetic variation contributes to antisocial and aggressive behaviours, including criminal acts; alongside this, the debate about how such scientific findings could affect criminal law and potentially mitigate criminal responsibility has re-emerged. However, the heritability of impulsive aggression and antisocial criminal behaviours is far from established, and there is little evidence to suggest that a genetic predisposition toward aggression and/or violence should mitigate moral or legal liability during criminal sentencing. There is thus a danger that any (even partial) attribution of biological causes to criminal acts will be misinterpreted as reductionist determinism. It is imperative that simplistic causal relationships between genetic variants and aggressive or violent behaviour are avoided. Genetic susceptibility is probabilistic in nature: there are no such things as ’criminal genes’, but rather there appear to be common genetic variants that interact with other biological and environmental exposures to potentially increase or decrease risk for impulsive, aggressive, or violent behaviours. In parallel, complex ethical dilemmas regarding the use of genomic data housed in both medical and forensic DNA biobanks for use in criminal proceedings continue to be debated in this era of big data.

Background Maltreated children are at risk of poor educational outcomes, but also experience greater individual, family, and neighbourhood adversities that may obscure an understanding of relationships between child protection involvement and educational attainment. Objective To examine associations between child protection involvement and 3rd- and 5th-grade reading and numeracy attainment, while controlling multiple other adversities. Participants and Setting Participants were 56,860 Australian children and their parents from the New South Wales Child Development Study with linked multi-agency records. Methods Multinomial logistic regressions examined associations between level of child protection involvement (Out-Of-Home Care [OOHC] placement; substantiated Risk Of Significant Harm [ROSH]; unsubstantiated ROSH; non-ROSH; and no child protection report) and standardised tests of 3rd- and 5th-grade reading and numeracy. Fully adjusted models controlled demographic, pregnancy, birth, and parental factors, and early (kindergarten) developmental vulnerabilities on literacy and numeracy, and other developmental domains (social, emotional, physical, communication). Results All children with child protection reports were more likely to attain below average, and less likely to attain above average, 3rd- and 5th-grade reading and numeracy, including children with reports below the ROSH threshold. Children with substantiated ROSH reports who were not removed into care demonstrated the worst educational attainment, with some evidence of protective effects for children in OOHC. Conclusions A cross-agency response to supporting educational attainment for all children reported to child protection services is required, including targeted services for children in OOHC or with substantiated ROSH reports, and referral of vulnerable families (unsubstantiated and non-ROSH cases) to secondary service organisations (intermediate intervention).

Though the positive association between a connection to the natural environment and well-being is well established, few studies have examined this association in children, and none have explored whether this relationship remains when accounting for other factors that affect well-being, such as social supports, attention, and empathic skills. The current study aims to address this gap. Data are drawn from the New South Wales Child Development Study (NSW-CDS) and comprise a representative sample of 26,848 children who completed a self-report survey of mental health and well-being when aged approximately 11 years. Multiple regression analysis indicated that, after adjusting for covariates (i.e., social supports, empathy, attention, socioeconomic status, and sex), connection to nature was positively, albeit weakly, associated with two indicators of well-being: self-satisfaction and prosocial behavior. Social supports had the strongest relationship with self-satisfaction, while empathy had the strongest relationship with prosocial behavior. Based on our findings, and that of previous research, we suggest that developing a connection to nature can slightly improve well-being and may complement or augment other well-being and education-based programs. Future research should examine whether the relationship between connection to nature and well-being is influenced by proximity to green spaces, experiences of nature, and age.

This paper describes the development of a brief school-based instrument designed for use in research and in educational practice. The Survey of School Promotion of Emotional and Social Health differentiates states of high, moderate, and low implementation of whole-school policies and practices that promote the emotional and social health of students. The instrument measures the extent to which a school has implemented policies and practices in four health-promoting domains: (a) creating a positive school community, (b) teaching social and emotional skills, (c) engaging the parent community, and (d) supporting students experiencing mental health difficulties. Responses were gathered via an online survey of Principals in almost 600 Australian primary schools in New South Wales. Preliminary psychometric properties of the instrument, and the development of an implementation index using latent class analysis, are described. The final 13-item version of the survey has broad applicability for use by researchers and evaluators for comparative and multivariate analyses. School leadership may find it useful as a brief tool to guide the identification of target areas for whole-school improvement across the four important health-promoting domains.

Learning the causal relation between actions and their outcomes (AO learning) is critical for goal-directed behavior when actions are guided by desire for the outcome. This can be contrasted with habits that are acquired by reinforcement and primed by prevailing stimuli, in which causal learning plays no part. Recently, we demonstrated that goal-directed actions are impaired in schizophrenia; however, whether this deficit exists alongside impairments in habit or reinforcement learning is unknown. The present study distinguished deficits in causal learning from reinforcement learning in schizophrenia. We tested people with schizophrenia (SZ, n = 25) and healthy adults (HA, n = 25) in a vending machine task. Participants learned two action–outcome contingencies (e.g., push left to get a chocolate M&M, push right to get a cracker), and they also learned one contingency was degraded by delivery of noncontingent outcomes (e.g., free M&Ms), as well as changes in value by outcome devaluation. Both groups learned the best action to obtain rewards; however, SZ did not distinguish the more causal action when one AO contingency was degraded. Moreover, action selection in SZ was insensitive to changes in outcome value unless feedback was provided, and this was related to the deficit in AO learning. The failure to encode the causal relation between action and outcome in schizophrenia occurred without any apparent deficit in reinforcement learning. This implies that poor goal-directed behavior in schizophrenia cannot be explained by a more primary deficit in reward learning such as insensitivity to reward value or reward prediction errors.

Out-of-school suspension is associated with adverse educational, justice, health, and welfare outcomes. Little research has focussed on suspensions from primary (elementary) school, despite early exclusions representing high-risk events for poor outcomes. This study aimed to identify early life predictors of primary school suspensions in a sample of 34,855 Australian children using linked education, health, child protection, and justice records for children and their parents. Associations between 26 sociodemographic, pregnancy/birth, child, and parent factors (measured prior to 3rd grade) and subsequent suspensions, issued during the 3rd through 6th grades (ages ~8–11 years), were examined in bivariate and multivariable logistic regressions. In the fully adjusted model, 18 factors were associated with suspension, with the largest effects for male gender, child protection services contacts, and aggressive behaviour. Identification of students at risk of early suspension using multi-sector information available at school entry may assist educators and policymakers to deliver preventative interventions.

Childhood trauma is a risk factor for schizophrenia that affects brain functions associated with higher cognitive processes, including social cognition. Alterations in Theory-of-Mind (ToM), or mentalizing skills, are a hallmark feature of schizophrenia, and are also evident in individuals exposed to childhood trauma. However, the impact of childhood trauma exposure on brain function during social cognition in schizophrenia remains unclear. We thus examined the association between childhood trauma and brain function during the performance of a ToM task in 47 patients diagnosed with schizophrenia or schizoaffective disorder. All participants completed the Childhood Trauma Questionnaire (CTQ) and underwent functional magnetic resonance imaging while performing an established visual-cartoon affective ToM task. Whole-brain multiple regression analysis was performed on ToM-related brain activation, with CTQ total score as regressor of interest, while accounting for the effects of age, sex, diagnosis, symptom severity, behavioural performance, intelligence and medications levels. First, using a small-volume correction approach within a mask made of key regions for ToM [including bilateral temporo-parietal junctions (TPJ), medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC)/precuneus], total CTQ scores were positively associated with activation of the PCC/precuneus. Second, exploratory analyses for the rest of the brain (i.e., ROIs masked-out), revealed a positive association between trauma exposure and activation of the dorsomedial prefrontal cortex (dmPFC), and a negative association with activation of the anterior section of the TPJ. These results suggest that childhood trauma exposure may, at least partially, contribute to functional alterations of brain regions essential for effective mental state inference in schizophrenia.

Purpose To examine the impact of parental criminal offending, both paternal and maternal, on offspring aggression at age 5 years, while also considering key risk factors, including parental mental illness, child’s sex, and socioeconomic disadvantage. Methods The sample comprised 69,116 children, with linked parental information, from the New South Wales Child Development Study, a population-based multi-agency, multi-generational record linkage study that combines information from a teacher-reported cross-sectional survey of early childhood development at age 5 years (the 2009 Australian Early Development Census; AEDC) with data obtained via administrative records from multiple sources (e.g., health, crime, education, and welfare). Hierarchical logistic regression analyses were conducted to determine the effects of maternal and paternal criminal court appearances (frequency and type of offending), and mental health service contacts, on offspring aggression measured in the AEDC. Results Having a parent with a history of offending was significantly associated with high levels of offspring aggression in early childhood. The strength of association was greatest when parents were involved in frequent (≥6 offences: adjusted odds ratio [aOR] range = 1.55–1.73) and violent (aOR range = 1.49–1.63) offending. Both maternal and paternal offending remained significant predictors of offspring aggression after accounting for parental mental illness, and associations were similar in magnitude for maternal and paternal offending histories. Conclusions Parental history of severe criminal offending increased the risk of high levels of aggression in offspring during early childhood, highlighting the need for intervention with families during this key developmental period.

Background Cognitive heterogeneity in schizophrenia spectrum disorders (SSD) and bipolar disorder (BD) has been explored using clustering analyses. However, the resulting subgroups have not been cognitively validated beyond measures used as clustering variables themselves. We compared the emergent cross-diagnostic subgroups of SSD and BD patients on measures used to classify them, and also across a range of alternative cognitive measures assessing some of the same constructs. Method Domain scores from the Matrics Consensus Cognitive Battery were used in a cross-diagnostic clustering analysis of 86 patients with SSD (n = 45) and BD (n = 41). The emergent subgroups were then compared to each other and healthy controls (n = 76) on these and alternative measures of these domains, as well as on premorbid IQ, global cognition and a proxy of cognitive decline. Results A three-cluster solution was most appropriate, with subgroups labelled as Globally Impaired, Selectively Impaired, and Superior/Near-Normal relative to controls. With the exception of processing speed performance, the subgroups were generally differentiated on the cognitive domain scores used as clustering variables. Differences in cognitive performance among these subgroups were not always statistically significant when compared on the alternative cognitive measures. There was evidence of global cognitive impairment and putative cognitive decline in the two cognitively impaired subgroups. Limitations For clustering analysis, sample size was relatively small. Conclusions The overall pattern of findings tentatively suggest that emergent cross-diagnostic cognitive subgroups are not artefacts of the measures used to define them, but may represent the outcome of different cognitive trajectories.

Objectives: Childhood psychotic-like experiences (PLEs) increase risk for concurrent and future psychiatric disorders but are common in the population. Strategies are needed to identify vulnerable individuals who may benefit from monitoring or targeted intervention. This study aimed to delineate profiles of childhood PLEs that might be differentially associated with other psychopathologies, and multiple psychopathology. Design: Cross-sectional, online self-report survey. Methods: Participants were 27,000 Australian children from a population cohort (13,416 girls; mean age 11.91 years) who completed an online self-report questionnaire assessing PLEs (hallucinations and delusions) and Emotional, Peer Relationship, Conduct, and Hyperactivity–Inattention psychopathology. Latent class analysis differentiated classes of children showing different patterns of PLE responses, and multinomial logistic regression determined the association between the PLE classes and the various psychopathologies, adjusted for demographic covariates and the other psychopathologies. Results: Five latent profiles of PLE responses were characterized as follows: None (27.4% of children), Minor (29.7%), Moderate (11.8%), Hallucinatory (21.0%), and Strong (10.2%). These classes showed distinct associations with other psychopathologies (odds ratios between 1.27 and 4.58), and dose–response relationships indicated increasing likelihood of multiple psychopathology for the Hallucinatory and Strong classes (odds ratio = 21.87 for ≥3 psychopathologies in the Strong class). Conclusions: Tailored interventions that address the particular needs of these different classes of individuals may be warranted. Practitioner points: Children aged 11–12 years who report psychotic-like experiences (PLEs) can be classified into five different PLE profiles based on self-reported questionnaire responses, which may reflect different pathological processes. These PLE profiles show different patterns and magnitudes of increased risk for other types of psychopathology, and multiple psychopathology, suggesting that they present different treatment needs. Cross-sectional investigation of the associations between PLE profiles and other psychopathologies limits any conclusions as to the causal direction of these relationships. Multi-informant reports of psychopathology were unavailable.

Background: Alzheimer’s disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer’s Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect). Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP. Copyright © 2019 Drange, Smeland, Shadrin, Finseth, Witoelar, Frei, Psychiatric Genomics Consortium Bipolar Disorder Working Group, Wang, Hassani, Djurovic, Dale and Andreassen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

BackgroundParental criminal offending is an established risk factor for offending among offspring, but little evidence is available indicating the impact of offending on early childhood functioning. We used data from a large Australian population cohort to determine associations between exposure to parental offending and a range of developmental outcomes at age 5 years.MethodMulti-generation data in 66 477 children and their parents from the New South Wales Child Development Study were combined using data linkage. Logistic and multinomial regressions tested associations between any and violent offending histories of parents (fathers, mothers, or both parents) obtained from official records, and multiple measures of early childhood developmental functioning (social, emotional–behavioural, cognitive, communication and physical domains) obtained from the teacher-reported 2009 Australian Early Development Census.ResultsParental offending conferred significantly increased risk of vulnerability on all domains, particularly the cognitive domain. Greater risk magnitudes were observed for offending by both parents and by mothers than by fathers, and for violent than for any offending. For all parental offending exposures, vulnerability on multiple domains (where medium to large effects were observed) was more likely than on a single domain (small to medium effects). Relationships remained significant and of comparable magnitude following adjustment for sociodemographic covariates.ConclusionsThe effect of parental offending on early childhood developmental outcomes is pervasive, with the strongest effects on functioning apparent when both parents engage in violent offending. Supporting affected families in early childhood might mitigate both early developmental vulnerability and the propensity for later delinquency among these offspring.

Childhood trauma is a significant risk factor for the development of psychotic disorders, and may influence executive brain functions. We thus set out to investigate the long-term effects of childhood trauma exposure on brain function of adult chronic patients diagnosed with schizophrenia, schizoaffective disorder and (psychotic) bipolar-I disorder while performing a standard 2/0-back working memory task. Participants were 50 cases diagnosed with schizophrenia/schizoaffective disorder (SCZ), 42 cases with bipolar-I disorder (BD), and 47 healthy controls (HC). Among this sample, 56 clinical cases (SCZ = 32; BD = 24) and 17 HC reported significant levels of childhood trauma, while 36 clinical cases (SCZ = 18; BD = 18) and 30 HC did not. Effects of childhood trauma on working memory-related brain activation were examined in combined samples of clinical cases (independently of diagnosis) relative to HCs, as well as within each diagnostic category. Case-control analyses revealed increased activation of the left inferior parietal lobule as a main effect of trauma exposure. In addition, trauma exposure interacted with a diagnosis of SCZ or BD to reveal trauma-related increased activation in the cuneus in clinical cases and decreased activation in this region in controls. Disorder-specific functional alterations were also evident in the SCZ sample, but not BD. Childhood trauma exposure elicits aberrant function of parietal regions involved in working memory performance regardless of clinical status, as well as task-relevant visual regions that participates to attentional processes. Childhood trauma may therefore contribute to alterations in attention in SCZ and BD while performing an n-back working memory task.

Cognitive deficits are a core feature of schizophrenia and contribute significantly to functional disability. We investigated the molecular pathways associated with schizophrenia (SZ; n=47) cases representing both 'cognitive deficit' (CD; n=22) and 'cognitively spared' (CS; n=25) subtypes of schizophrenia (based on latent class analysis of 9 cognitive performance indicators), compared with 49 healthy controls displaying 'normal' cognition. This was accomplished using gene-set analysis of transcriptome data derived from peripheral blood mononuclear cells (PBMCs). We detected 27 significantly altered pathways (19 pathways up-regulated and 8 down-regulated) in the combined SZ group and a further 6 pathways up-regulated in the CS group and 5 altered pathways (4 down-regulated and 1 up-regulated) in the CD group. The transcriptome profiling in SZ and cognitive subtypes were characterized by the up-regulated pathways involved in immune dysfunction (e.g., antigen presentation in SZ), energy metabolism (e.g., oxidative phosphorylation), and down-regulation of the pathways involved in neuronal signaling (e.g., WNT in SZ/CD and ERBB in SZ). When we looked for pathways that differentiated the two cognitive subtypes we found that the WNT signaling was significantly down-regulated (FDR

Evidence from experimental psychology provides unequivocal support for enhanced creativity among individuals who are prone to psychotic and mood disorders. At the same time, there is strong epidemiological evidence for greater incidence of creative achievement among those diagnosed with bipolar disorder (but not schizophrenia). This review examines the evidence for common factors predisposing an individual to creativity and psychosis, as well as factors that distinguish the capacity for creative achievement from the creative potential that may be inherent in psychosis vulnerability. Factors implicated as common to creative potential and psychosis vulnerability include enhanced divergent thinking, reduced latent inhibition and preattentive filtering mechanisms; on the other hand, greater cognitive flexibility, motivation, and openness to experience tend to be associated with creative achievement, but not psychosis. This evidence is considered with respect to the utility of tailored vocational interventions...

Background Cortical neuroanatomical abnormalities have been reported along a continuum between individuals with chronic schizophrenia, first-episode psychosis, clinical high risk for psychosis, and healthy individuals self-reporting subclinical psychotic-like experiences (or schizotypy). Recently, the Schizophrenia Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust cortical thickness abnormalities in schizophrenia, while also indicating that these abnormalities are influenced by illness severity and treatment with antipsychotic medications. In this context, schizotypy research allows the investigation of cortical neuroanatomy associated with the expression of subclinical psychotic-like symptoms without the potential influence of a psychotic illness, its severity, or the use of antipsychotics. This study presents the first large-scale imaging meta-analysis of cortical thickness in schizotypy using standardized methods from 23 datasets worldwide. Methods Cortical thickness and surface area were assessed in MRI scans of 2,695 healthy individuals (mean [range] age of 29.1 [17–55.8], 46.3% male) who had also completed validated self-report schizotypy questionnaires. Each site processed their local T1-weighted MRI scans using FreeSurfer and, following the protocol outlined in the ENIGMA Schizophrenia Working Group study, extracted cortical thickness for 70 Desikan-Killiany (DK) atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness). At each site, partial correlation analyses were performed between regional cortical thickness by ROI and total schizotypy scores in R, predicting the left, right and mean cortical thickness, adjusting for sex, age and site. Random-effects meta-analyses of partial correlation effect sizes for each of the DK atlas regions were performed using R’s metafor package. False discovery rate (pFDR < .05) was used to control for multiple comparisons. Results We found significant positive associations between subclinical psychotic-like experiences and mean cortical thickness of the medial orbitofrontal cortex (r = .077; pFDR = .006) and the frontal pole (r = .073; pFDR = .006). When assessed separately by hemisphere, meta-analysis revealed a significant positive association between subclinical psychotic-like experiences and cortical thickness of the left medial orbitofrontal cortex (r = .066; pFDR = .044), and at trend-level with the right medial orbitofrontal cortex (r = .062; pFDR = .053) and the left frontal pole (r = .062; pFDR = .053). No significant associations were observed for surface area. Discussion Worldwide cooperative analyses of large-scale brain imaging data support a profile of cortical thickness abnormalities involving prefrontal cortical regions positively related to schizotypy in healthy individuals. These findings are not secondary to potential influences of disease chronicity or antipsychotic medication on the neuroanatomical correlates of psychotic-like experiences. The directionality of the observed meta-analytical effects in schizotypy is opposite to those previously reported in patients with schizophrenia (i.e., thinner cortex). The present findings of increased thickness may indicate early microstructural deficits (e.g. in myelination) that contribute to vulnerability for psychosis. Alternatively, these may reflect mechanisms of resilience associated with the expression of subclinical manifestations of psychotic symptoms in otherwise healthy individuals.

Highlights • We determined the extent of gender-specific intergenerational antisocial behavior. • Gender-specific associations were not larger than associations across-gender. • The largest associations were between mothers' and daughters' antisocial behavior.

The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Prior investigations indicate that the five core personality dimensions (the “Big Five”) are measurable by middle childhood. The aim of this research was to examine the psychometric properties of a short-form self-report measure of the Big Five personality dimensions in children that would be suitable for administration online in large population-based studies. Twenty-five questionnaire items in English, derived from the 65-item Big Five Questionnaire for Children in Italian (Barbaranelli, Caprara, Rabasca, & Pastorelli, 2003), were completed online by 27,415 Australian children in Year 6 (mean age 11.92 years). An item response theory approach evaluated the psychometric properties and resolved a 20-item short-form questionnaire. Exploratory and confirmatory factor analyses supported the Big Five structure. Construct validity was demonstrated via correlations between Big Five scores and the Strengths and Difficulties Questionnaire subscales (Goodman, 2001). The 20 items provide a brief, reliable, and valid child self-report measure of the Big Five personality dimensions. Read More: https://guilfordjournals.com/doi/10.1521/pedi_2018_32_380

Although parental criminal offending is a recognized risk factor for conduct problems among offspring, its impact on the continuity and discontinuity of children’s behavioural and emotional difficulties during the early development is less well known. We used data from a large, population-based record-linkage project to examine the relationship between parental offending and the continuity and discontinuity of children’s conduct, attentional, and emotional difficulties from early to middle childhood while also considering the role of timing of the parental offending exposure. Data for 19,208 children and their parents were drawn from the New South Wales Child Development Study. Multinomial regression analyses tested associations between mother’s and father’s history and timing of any and violent offending, and patterns of continuity or discontinuity in offspring emotional, conduct, and attentional difficulties between ages 5 and 11 years. Maternal and paternal offending each conferred a significantly increased risk of all the patterns of developmental difficulties, including those limited to age 5 only (remitting problems), to age 11 only (incident problems), and to difficulties present at both ages 5 and 11 years (persisting problems). Greatest odds were observed for persisting conduct problems. Paternal offending that continued through early and middle childhood had the greatest association with child difficulties, while the timing of maternal offending had a less prominent effect on child developmental difficulties. Parental offending is a strong risk factor for early and pervasive behavioural and emotional problems in offspring, and may be a key indicator of high risk for later antisocial behaviour.

Increasing evidence suggests that the intergenerational transmission of antisocial behaviour begins from the earliest childhood developmental periods. This chapter presents findings on the role of parental offending on offspring developmental vulnerability in early childhood. Data were drawn from the New South Wales Child Development Study, a large Australian population-based, multi-agency, intergenerational study that utilises administrative record linkage of data from multiple sources (i.e., criminal justice, health, welfare, and education). The present chapter focuses on the associations between parental criminal offending and offspring outcomes at age 5 years as measured by the Australian Early Development Census (AEDC). The AEDC is a teacher-reported cross-sectional assessment that captured 99.9 per cent (N = 87,026) of the eligible New South Wales children entering kindergarten in the state of New South Wales in 2009, indexing early childhood developmental functioning across five domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive development, and communication and general knowledge). Results showed that both maternal and paternal offending were associated with offspring vulnerability on all five of the AEDC domains as well as on the aggression subdomain, even after accounting for other important risk factors (e.g., child sex, socio-economic disadvantage). Findings suggest that the effects of parental offending may be pervasive in early childhood, with multiple developmental outcomes affected, especially cognitive functioning. A second record linkage was conducted in 2016 to bring data up to age 12 years for the children, and we plan to conduct follow-up studies with the cohort into adulthood using successive waves of record linkage.

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30 000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.

Objectives Childhood trauma is a common risk factor for adult psychiatric disorders, such as schizophrenia (SZ) and bipolar-I disorder (BD). However, its association with schizotypal personality traits, as well as cognitive and social cognitive abilities, is less well studied in these populations. Methods In a cohort of 79 SZ cases, 84 BD cases, and 75 healthy controls (HCs), clinically significant levels of childhood trauma exposure (according to scores on the Childhood Trauma Questionnaire; CTQ) were evident in 54 SZ, 55 BD, and 26 HC individuals. Trauma-exposed and non-exposed groups were compared on schizotypal personality features (schizotypy) measured with the Schizotypal Personality Questionnaire (SPQ). Cognitive assessments included executive function, working memory, attention, and immediate and delayed memory. Social cognitive measures assessed facial emotion processing and theory-of-mind abilities. Results Trauma-exposed participants showed higher levels of schizotypy, especially suspiciousness, relative to non-exposed individuals, regardless of clinical or HC status. Furthermore, trauma-exposed individuals showed deficits specifically in social cognitive, but not general cognitive abilities, regardless of clinical or HC status. These trauma-related results were found in the context of higher schizotypy levels in both SZ and BD relative to HC, and lower cognitive and social cognitive performance in SZ, relative to BD and HC groups. Conclusions These findings suggest that childhood trauma exposure impacts long-term schizotypy outcomes, especially paranoid ideation (suspiciousness), as well as complex social cognitive abilities in both healthy and psychotic populations. However, cognitive deficits associated with psychotic illness may not be distinguishable from those related to trauma exposure in previous studies. Practitioner points Findings Childhood trauma exposure is associated with increased schizotypal features (in particular paranoid ideation) and complex social cognitive abilities, independently of the diagnosis of psychotic disorder. Cognitive and social cognitive deficits were larger in schizophrenia compared to bipolar-I cases and healthy controls, but increased schizotypal features were observed in both schizophrenia and bipolar-I disorder relative to healthy controls. Limitations We were unable to distinguish the specific effects of particular childhood trauma exposures due to the high rate of exposure to more than one type of maltreatment. Retrospective assessment of childhood trauma in adulthood cannot be externally validated, and associations with behavioural traits in later life may be confounded by other factors not studied here.

Background Fetal exposure to infectious and noninfectious diseases may influence early childhood developmental functioning, on the path to later mental illness. Here, we investigated the effects of in utero exposure to maternal infection and noninfectious diseases during pregnancy on offspring developmental vulnerabilities at age 5 years, in the context of estimated effects for early childhood exposures to infectious and noninfectious diseases and maternal mental illness. Methods We used population data for 66,045 children from an intergenerational record linkage study (the New South Wales Child Development Study), for whom a cross‐sectional assessment of five developmental competencies (physical, social, emotional, cognitive, and communication) was obtained at school entry, using the Australian Early Development Census (AEDC). Child and maternal exposures to infectious or noninfectious diseases were determined from the NSW Ministry of Health Admitted Patients Data Collection (APDC) and maternal mental illness exposure was derived from both APDC and Mental Health Ambulatory Data collections. Multinomial logistic regression analyses were used to examine unadjusted and adjusted associations between these physical and mental health exposures and child developmental vulnerabilities at age 5 years. Results Among the physical disease exposures, maternal infectious diseases during pregnancy and early childhood infection conferred the largest associations with developmental vulnerabilities at age 5 years; maternal noninfectious illness during pregnancy also retained small but significant associations with developmental vulnerabilities even when adjusted for other physical and mental illness exposures and covariates known to be associated with early childhood development (e.g., child's sex, socioeconomic disadvantage, young maternal age, prenatal smoking). Among all exposures examined, maternal mental illness first diagnosed prior to childbirth conferred the greatest odds of developmental vulnerability at age 5 years. Conclusions Prenatal exposure to infectious or noninfectious diseases appear to influence early childhood physical, social, emotional and cognitive developmental vulnerabilities that may represent intermediate phenotypes for subsequent mental disorders.

This study examined the structure of the Best Start Kindergarten Assessment (Best Start) of literacy and numeracy, with the aim of confirming a two-factor measure of attainment at school entry comparable in structure to standardised measures of literacy and numeracy administered in later school years. Administrative data from the 2009 Best Start were obtained from the New South Wales Department of Education for 37,734 children aged ∼5 years (i.e. as they entered their first year of compulsory schooling) as part of the New South Wales Child Development Study. Exploratory and confirmatory factor analyses were performed on the 11 Best Start scales using a split half methodology, with the findings supporting a two-factor solution underpinning literacy and numeracy attainment. The availability of this two-factor Best Start measure of literacy and numeracy at school entry, which precedes the repeated national assessments conducted later in the primary and high school years, facilitates research to examine pathways of academic performance over time.

BackgroundThe intergenerational risk for mental illness is well established within diagnostic categories, but the risk is unlikely to respect diagnostic boundaries and may be reflected more broadly in early life vulnerabilities. We aimed to establish patterns of association between externalising and internalising vulnerabilities in early childhood and parental mental disorder across the full spectrum of diagnoses.MethodsA cohort of Australian children (n = 69 116) entering the first year of school in 2009 were assessed using the Australian Early Development Census, providing measures of externalising and internalising vulnerability. Parental psychiatric diagnostic status was determined utilising record-linkage to administrative health datasets.ResultsParental mental illness, across diagnostic categories, was associated with all child externalising and internalising domains of vulnerability. There was little evidence to support interaction by parental or offspring sex.ConclusionsThese findings have important implications for informing early identification and intervention strategies in high-risk offspring and for research into the causes of mental illness. There may be benefits to focusing less on diagnostic categories in both cases.

This study examined associations between maltreatment and early developmental vulnerabilities in a population sample of 68,459 children (M-age=5.62years, SD=.37) drawn from the Australian state of New South Wales, using linked administrative data for the children and their parents (collected 2001-2009). Associations were estimated between (a) any maltreatment, (b) the number of maltreatment types, and (c) the timing of first reported maltreatment and vulnerability and risk status on multiple developmental domains (i.e., physical, social, emotional, cognitive, and communication). Pervasive associations were revealed between maltreatment and all developmental domains; children exposed to two or more maltreatment types, and with first maltreatment reported after 3 years of age, showed greater likelihood of vulnerability on multiple domains, relative to nonmaltreated children. Refereed/Peer-reviewed

GRM5 (coding for metabotropic glutamate receptor 5, mGluR5) is a promising target for the treatment of cognitive deficits in schizophrenia, but there has been little investigation of its association with cognitive and brain phenotypes within this disorder. We examined the effects of common genetic variation in GRM5 with cognitive function, hippocampal volume, and hippocampal mGluR5 protein levels in schizophrenia patients relative to healthy controls. Two independent GRM5 variants rs60954128 [C>T] and rs3824927 [G>T] were genotyped in a schizophrenia case/control cohort (n=249/261). High-resolution anatomical brain scans were available for a subset of the cohort (n=103 schizophrenia /78 control). All participants completed a standard set of neuropsychological tests. In a separate postmortem cohort (n=19 schizophrenia/20 controls), hippocampal mGluR5 protein levels were examined among individuals of different GRM5 genotypes. Schizophrenia minor allele carriers of rs60954128 had reduced right hippocampal volume relative to healthy controls of the same genotype (-12.3%); this effect was exaggerated in males with schizophrenia (-15.6%). For rs3824927, compared to major allele homozygotes, minor allele carriers with schizophrenia had lower Intelligence Quotients (IQ). Examination in hippocampal postmortem tissue showed no difference in mGluR5 protein expression according to genotype for either rs60954128 or rs3824927. While these genetic variants in GRM5 were associated with cognitive impairments and right hippocampal volume reduction in schizophrenia, they did not affect protein expression. Further study of these mechanisms may help to delineate new targets for the treatment of cognitive deficits in schizophrenia, and may be relevant to other disorders.

BACKGROUND: Neuroanatomical studies have provided some evidence for a neurobiological continuity between psychotic symptoms in patients with schizophrenia and subclinical psychotic-like experiences as identified via self-report questionnaires (or schizotypy) in otherwise healthy individuals. Despite a number of structural brain imaging studies published in subjects with schizotypy, these have often been limited by relatively small sample sizes. This study represents the first meta-analysis of structural MRI scans in schizotypy assessed with standardized methods at 17 centres worldwide. METHODS: The total sample included in the case-control meta-analysis involved 496 subjects with high schizotypy and 588 comparison subjects with low schizotypy as identified with validated self-report schizotypy questionnaires (i.e., the Community Assessment of Psychic Experiences, the Oxford-Liverpool Inventory of Feelings and Experiences, or the Schizotypal Personality Questionnaire). Left and right lateral ventricle, thalamus, caudate, putamen, pallidum, accumbens, hippocampus and amygdala volumes, as well as intracranial volumes (ICV), were obtained with FreeSurfer from high-resolution T1-weighted structural brain scans locally by each site. Analyses of individual subject data were also performed by the site that contributed the sample, using code created within the ENIGMA collaboration. Group differences for each ROI within each sample were examined using univariate linear regression analysis in R predicting the left, right and mean subcortical volumes with group (low or high schizotypy) controlling for age, sex, site and ICV. For each sample, Cohen’s d effect sizes for each ROI were computed based on the group contrast t-statistics. Random-effects meta-analyses of Cohen’s d effect sizes for each ROI were performed using R’s metafor package. RESULTS: For the case-control meta-analysis, mean (range) age across samples was 29.2 (19.2–44.9) years for subjects with high schizotypy and 28.5 (19.4–42.5) years for subjects with low schizotypy. High and low schizotypy samples were on average 48.6% (25–100) and 49.0% (8–100) male. Compared to low schizotypy, people with high schizotypy had smaller left nucleus accumbens volumes (Cohen’s d = -0.13, p = 0.04). No other significant meta-analytical effects were identified. DISCUSSION: Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities involving the ventral striatum in healthy individuals with subclinical psychotic-like experiences. Though the effect size is small, the result is consistent with findings in schizophrenia patients and suggesting that these effects are not secondary to potential influences of disease chronicity or antipsychotic medication. The lack of significant effects in other reported regions in schizophrenia research may indicate that further subcortical abnormalities may not be present or detectable in schizotypy samples and could reflect mechanisms of resilience in this population.

The relationship between learned variations in attention and schizotypy was examined in two experiments. In Experiment 1, participants low on a negative subscale of schizotypy exhibited an explicit bias in overt attention towards stimuli that were established as predictive of a trial outcome, relative to stimuli that were irrelevant. The same participants also showed a bias in learning about these stimuli when they presented in a novel context. Neither of these effects was observed in participants high in schizotypy. In Experiment 2, participants low on the negative subscale of schizotypy exhibited faster reaction times towards a target that was cued by a stimulus that had a history of predictive validity relative to a stimulus that had a history of irrelevance. Again, this effect was not present in participants high in schizotypy. These results imply a disruption in the normal allocation of attention to cues that have predictive significance in schizotypy.

BackgroundImpairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives.MethodNeurocognitive and social cognitive ability was examined in 99 young people (age range 16–30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD.ResultsOnly verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs.ConclusionsSelective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

Common variants of the FK506 binding protein 5 (FKBP5) gene are implicated in psychotic and other disorders, via their role in regulating glucocorticoid receptor (GR) receptor sensitivity and effects on the broader function of the HPA system in response to stress. In this study, the effects of four FKBP5 polymorphisms (rs1360780, rs9470080, rs4713902, rs9394309) on IQ and eight other cognitive domains were examined in the context of exposure to childhood maltreatment in 444 cases with schizophrenia and 292 healthy controls (from a total sample of 617 cases and 659 controls obtained from the Australian Schizophrenia Research Bank; ASRB). Participants subjected to any kind of maltreatment (including physical, emotional, or sexual abuse or physical or emotional neglect) in childhood were classified as 'exposed'; cognitive functioning was measured with Repeatable Battery for the Assessment of Neuropsychological Status, the Controlled Oral Word Association Test, and IQ was estimated with the Weschler Test of Adult Reading. Hierarchical regressions were used to test the main effects of genotype and childhood maltreatment, and their additive interactive effects, on cognitive function. For rs1360870, there were significant main effects of genotype and childhood maltreatment, and a significant interaction of genotype with childhood trauma affecting attention in both schizophrenia and healthy participants (C-homozygotes in both groups showed worse attention in the context of maltreatment); in SZ, this SNP also affected global neuropsychological function regardless of exposure to childhood trauma, with T-homozygotes showing worse cognition than other genotypes. The mechanisms of trauma-dependent effects of FKBP5 following early life trauma deserve further exploration in healthy and psychotic samples, in the context of epigenetic effects and perhaps epistasis with other genes. Study of these processes may be particularly informative in subgroups exposed to various other forms of early life adversity (i.e., birth complications, immigration).

The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder.

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12-30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD ('AR'), b) participants from families without mental illness ('controls'), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.

Background Goal-directed actions depend on our capacity to integrate the anticipated consequences of an action with the value of those consequences, with the latter derived from direct experience or inferred from predictive stimuli. Schizophrenia is associated with poor goal-directed performance, but whether this reflects a deficit in experienced or predicted value or in integrating these values with action-outcome information is unknown, as is the locus of any associated neuropathology. Methods We assessed the contribution of these sources of value to goal-directed actions in people with schizophrenia (SZ) ( n = 18) and healthy adults ( n = 18). Participants learned to use specific actions to liberate snack foods from a vending machine. They also learned about the reward value of the foods, changes in reward value, and the relationship between various predictive stimuli and food delivery. We then evaluated the ability of subjects to use experienced or predicted value to guide goal-directed actions while undergoing functional magnetic resonance imaging. Results Acquisition and sensitivity to experienced changes in outcome value did not differ in SZ and healthy adults. The SZ were, however, deficient in their ability to integrate action-outcome learning with outcome values to guide choice, more so when actions were guided by experienced than by predicted values. These effects were differentially associated with reductions in activity in caudate and limbic structures, respectively. Conclusions This novel assessment of goal-directed learning revealed dysfunction in corticostriatal control associated with a profound deficit in integrating changes in experienced value with the action-outcome association in schizophrenia.