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Early life exposure to Domestic Violence and Abuse (DVA) is associated with poor psychosocial and cognitive development in childhood. However, most prior research uses mother-reported involvement in DVA as a proxy indicator of child exposure; studies using direct measures of child exposure to DVA are scarce, especially among representative population-based samples. We address this gap by using longitudinal, population-based data from an Australian record linkage study of children to examine the associations between early life exposure to DVA and early childhood developmental vulnerability. Exposure to DVA was measured using police contact records for children involved in a DVA incident either as a victim or witness. Developmental vulnerability at school entry was measured using the Australian Early Development Census, providing indices of five broad domains of function and person-centred classes of developmental risk (referred to as 'mild generalized risk', 'misconduct risk', and 'pervasive risk', each compared to a group showing 'no risk'). Children exposed to DVA showed significantly greater odds of developmental vulnerability on all five domains and were more likely to be members of the three developmental risk classes. Girls who were victims of DVA (OR = 1.65) had significantly poorer developmental outcomes than boys who were victims (OR = 1.26) within the domain of communication skills and general knowledge (d = 0.29 [SE = 0.16], p =.04). No other sex differences were found. These preliminary findings hold important implications for policy regarding the early intervention and implementation of support services for young children exposed to DVA. [ABSTRACT FROM AUTHOR]

Cross-agency administrative data can improve cost-effective triage systems for child protection and other human service delivery. To determine the minimum set of cross-agency indicators that could accurately classify placement in out-of-home-care (OOHC) before age 13–14 years. Participants were 72,079 Australian children (mean age = 13.16 years; SD = 0.37; 51.4% male) and their parents, for whom linked administrative records spanning the years 1994–2016 were available for analysis within the 'New South Wales Child Development Study'. First, a series of logistic regression analyses were conducted to examine associations between cross-agency (health, justice, education) risk indicators and membership of the sub-cohort of 1239 children who had an OOHC placement prior to age 13–14 years, relative to (1) the sub-cohort of 55,473 children who had no previous contact with child protection services, and (2) the sub-cohort of 15,367 children who had been reported to child protection services but had no record of OOHC placement. We then explored the classification characteristics associated with a smaller combination of risk factors, and the utility of specific familial risk factors, for classifying membership of the OOHC subgroup. A combination of six risk indicators evident before OOHC placement can classify children placed in OOHC with approximately 95% accuracy, and the presence of at least four of these risk indicators provides excellent specificity (99.6%). A combination of risk factors observable in administrative datasets held by multiple government agencies may be used to target support services to prevent entry into OOHC for children from vulnerable families. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Abstract: Objective: The FOXP2 gene is involved in the development of speech and language. As some single nucleotide polymorphisms (SNPs) of FOXP2 have been found to be associated with auditory verbal hallucinations (AVHs) at trend levels, this study set out to undertake the first examination into whether interactions between candidate FOXP2 SNPs and environmental factors (specifically, child abuse) predict the likelihood of AVHs. Method: Data on parental child abuse and FOXP2 SNPs previously linked to AVHs (rs1456031, rs2396753, rs2253478) were obtained from the Australian Schizophrenia Research Bank for people with schizophrenia-spectrum disorders, both with (n = 211) and without (n = 122) a lifetime history of AVHs. Results: Genotypic frequencies did not differ between the two groups; however, logistic regression found that childhood parental emotional abuse (CPEA) interacted with rs1456031 to predict lifetime experience of AVH. CPEA was only associated with significantly higher levels of AVHs in people with CC genotypes (odds ratio = 4.25), yet in the absence of CPEA, people with TT genotypes had significantly higher levels of AVHs than people with CC genotypes (odds ratio = 4.90). This interaction was specific to auditory verbal hallucinations, and did not predict the likelihood of non-verbal auditory hallucinations. Conclusions: Our findings offer tentative evidence that FOXP2 may be a susceptibility gene for AVHs, influencing the probability people experience AVHs in the presence and absence of CPEA. However, these findings are in need of replication in a larger study that addresses the methodological limitations of the present investigation. [Copyright &y& Elsevier]

Abstract: The interaction of genetic and environmental factors may affect the course and development of psychotic disorders. We examined whether the effects of childhood trauma on cognition and symptoms in schizophrenia were moderated by the Catechol-O-methyltransferase (COMT) Val158Met polymorphism, a common genetic variant known to affect cognition and prefrontal dopamine levels. Participants were 429 schizophrenia/schizoaffective cases from the Australian Schizophrenia Research Bank (ASRB). Cognitive performance was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Controlled Oral Word Association Test (COWAT), Letter Number Sequencing (LNS) test, and the Wechsler Test of Adult Reading (WTAR). Hierarchical regression was used to test the main effects and additive interaction effects of genotype and childhood trauma in the domains of physical abuse, emotional abuse, and emotional neglect, on cognition and symptom profiles of clinical cases. Consistent with previous findings, COMT Val homozygotes performed worse on cognitive measures in the absence of childhood adversity. In addition, a significant interaction between COMT genotype and physical abuse was associated with better executive function in Val homozygotes, relative to those of the same genotype with no history of abuse. Finally, the severity of positive symptoms was greater in Met carriers who had experienced physical abuse, and the severity of negative symptoms in Met carriers was greater in the presence of emotional neglect. These results suggest that the possible epigenetic modulation of the expression of the COMT Val158Met polymorphism and consequent effects on cognition and symptoms in schizophrenia, with worse outcomes associated with adverse childhood experiences in Met carriers. [Copyright &y& Elsevier]

Background: Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. Methods: Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). Results: Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). Conclusions: Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder. [ABSTRACT FROM AUTHOR]

Abstract: Accumulating evidence suggests high rates of personality disorder (PD) in schizophrenia (Sz), and as such, the implications of PD in this context are beginning to be studied more thoroughly. We examined clinical, cognitive and experiential (i.e., reported childhood adversity) correlates of aberrant personality traits in schizophrenia and healthy controls (HC) as measured by the International Personality Disorder Examination Questionnaire (IPDEQ). Participants were 549 individuals with schizophrenia or schizoaffective disorder, and 572 healthy adults recruited to the Australian Schizophrenia Research Bank (ASRB). Schizophrenia participants were significantly more likely than healthy controls to screen positive for personality disorder across all ICD-10 subtypes, and there was substantial overlap between clusters, with ∼33% of Sz participants screening positive for all 3 personality disorder clusters. Among both Sz and HC groups, cluster B personality characteristics were significantly associated with increased suicidal behaviours, lower cognitive performance, and the experience of childhood adversity. In addition, Cluster C personality features were associated with higher overall ratings of affective blunting in schizophrenia, and Cluster A personality features were associated with childhood ‘loss’ in HC participants only. The cumulative effects of screening positive for more than one personality disorder in Sz was associated with higher likelihood of suicidal behaviour, earlier age of onset of Sz, and poorer cognitive functioning. The results suggest that abnormal co-occurrence of personality traits across DSM-IV clusters is evident in a significant proportion of individuals with schizophrenia, and that these personality features impact significantly on clinical and cognitive characteristics of Sz. [Copyright &y& Elsevier]

Abstract: In schizophrenia, blunted affect has been argued to reflect difficulties with the amplification of emotion expressive behavior. The aim of the present study was to assess whether ostensibly healthy individuals vulnerable to schizophrenia present with similar difficulties. In the first component of the study, 843 non-clinical participants completed the Schizotypal Personality Questionnaire, of which 27 scoring in the upper 15% (high schizotypy group) and 27 scoring in the lower 15% (low schizotypy group) were asked to watch amusing film clips, whilst engaging in different emotion regulatory strategies, and specifically, amplify the expression of an experienced emotion (‘amplification’) or suppress the expression of an experienced emotion (‘suppression’). The results indicate that highly schizotypal participants present with specific difficulties with the amplification (but not suppression) of emotion expressive behavior. These difficulties are significantly correlated with total negative schizotypy, particularly blunted affect. In the second component of the study, an individual differences approach was used to assess the interrelationship between self-reported use of suppression and schizotypy in an independent sample of 204 community volunteers. The results suggest that, although blunted affect is associated with increased use of suppression, it cannot be regarded as the primary mechanism underpinning this disturbance. Implications for understanding blunted affect in schizophrenia and related disorders are discussed. [Copyright &y& Elsevier]

Rapid and efficient judgments about the significance of social threat are important for species survival and may recruit specialized neurocognitive systems, consistent with biological models of threat processing . We review cognitive, psychophysiological, neuropsychological, and neuroimaging evidence in support of specialized neural networks subserving the processing of facial displays of threat. Cognitive research suggests that faces depicting anger are detected quickly when presented amongst other facial expressions, on the basis of distinguishing facial features. Psychophysiological investigations using visual scanpath techniques provide evidence for increased foveal attention to facial features of threat-related expressions (anger, fear), which may facilitate rapid detection and subsequent appraisal of the significance of threat (such as the direction of impending threat). Neuropsychological and neuroimaging studies implicate a primary role for the amygdale and pre-frontal cortices in interpreting signs of danger from facial expressions and other social stimuli. Subtle disturbances in these neurocognitive systems underlying efficient threat detection (manifesting in attentional biases and aberrant neural activity) may result in abnormally heightened perception of social threat, as seen in clinical levels of social anxiety and/or persecutory delusions in schizophrenia. Clinical states of paranoia may therefore reflect normal variation (i.e. biases) in the adaptive mechanisms which have evolved, in the Darwinian sense, to facilitate efficient threat detection in humans. As such, clinical levels of paranoia may represent the inevitable cost of efficient threat perception—or ‘justified’ suspicion—that is necessary for survival of the human species. [Copyright &y& Elsevier]

This study examined visuo-cognitive processing of threat-related (anger, fear) and non-threat faces (happy, sad, neutral) in deluded schizophrenia (n=11), non-deluded schizophrenia (n=8), and healthy control (n=22) participants. Focal analyses examined scanpath aberrations for particular facial expressions in sub-groups of schizophrenia patients determined by the presence or absence of overt delusions. Deluded schizophrenia subjects exhibited significantly fewer fixations of shorter duration for all faces, and fewer fixations of reduced duration to the feature areas of negative facial expressions (anger, sad), compared with healthy controls. Compared with non-deluded schizophrenia subjects, deluded subjects exhibited fewer fixations to fear expressions and more fixations to the feature areas of happy expressions. These findings were revealed in the context of restricted scanning (reduced number and duration of fixations, shorter scanpath length and shorter duration of fixations to facial features) in the entire schizophrenia group (n=19) compared with healthy controls. The findings suggest a controlled attentional bias away from the feature areas of negative facial expressions in deluded schizophrenia, that is, specific to threat-related expressions compared with non-deluded schizophrenia subjects. This controlled bias away from negative social stimuli in deluded schizophrenia is discussed in terms of an attentional style of ‘vigilance–avoidance’ operating across early and late stages of information processing. [Copyright &y& Elsevier]

Unpacking molecular perturbations associated with features of schizophrenia is a critical step toward understanding phenotypic heterogeneity in this disorder. Recent epigenome-wide association studies have uncovered pervasive dysregulation of DNA methylation in schizophrenia; however, clinical features of the disorder that account for a large proportion of phenotypic variability are relatively underexplored. We comprehensively analyzed patterns of DNA methylation in a cohort of 381 individuals with schizophrenia from the deeply phenotyped Australian Schizophrenia Research Bank. Epigenetic changes were investigated in association with cognitive status, age of onset, treatment resistance, Global Assessment of Functioning scores, and common variant polygenic risk scores for schizophrenia. We subsequently explored alterations within genes previously associated with psychiatric illness, phenome-wide epigenetic covariance, and epigenetic scores. Epigenome-wide association studies of the 5 primary traits identified 662 suggestively significant (p < 6.72 × 10−5) differentially methylated probes, with a further 432 revealed after controlling for schizophrenia polygenic risk on the remaining 4 traits. Interestingly, we uncovered many probes within genes associated with a variety of psychiatric conditions as well as significant epigenetic covariance with phenotypes and exposures including acute myocardial infarction, C-reactive protein, and lung cancer. Epigenetic scores for treatment-resistant schizophrenia strikingly exhibited association with clozapine administration, while epigenetic proxies of plasma protein expression, such as CCL17, MMP10, and PRG2, were associated with several features of schizophrenia. Our findings collectively provide novel evidence suggesting that several features of schizophrenia are associated with alteration of DNA methylation, which may contribute to interindividual phenotypic variation in affected individuals. [ABSTRACT FROM AUTHOR]

The fourth annual fMRI Experience was held at the National Institutes of Health (NIH), in Bethesda, Maryland, USA, on 3–14 May 2002. The conference was organized jointly by research fellows at the NIH and Institute of Psychiatry (IoP) in London, and benefited from financial support from the National Institute of Mental Health (NIMH) Intramural Research Program, the NIMH Division of Intramural Training, and the Guarantors of Brain in association with the IoP. [ABSTRACT FROM AUTHOR]

• Longitudinal, population-based school-entry cohort of 91,631 children. • Half of children with police contact had prior contact with the child protection system. • Prior contact with the child protection system was associated with contact as a person of interest, victim and/or witness. • Children's early police contact may flag the need for early intervention. Child maltreatment is known to be associated with risk of later offending and victimisation in adolescence and adulthood, but only a few studies have examined justice system contact in childhood and none have focused on police contact. This study investigated the time to first contact with police in childhood (aged 13 years and younger) among children with prior child protection services contact. Using administrative data for 91,631 children from the New South Wales Child Development Study, Cox proportional hazards regression analyses were used to investigate the time to first contact with the police (for any reason, and specifically as a 'person of interest', 'victim' or 'witness') associated with prior child protection contact, during the observation period from birth to age 13 years. Multivariate models controlled for sex, Aboriginal and/or Torres Strait Islander background, and socioeconomic disadvantage. Subgroup analyses were also conducted for boys and girls separately. Among the 14,323 children with any police contact by age 13 years, around half (52.3 %) had prior contact with the child protection system. Higher rates of police contact for any reason (HR = 4.45 [95 % CI = 4.08–4.86]), and as a person of interest (HR = 9.57 [95 % CI = 6.85–13.38]), victim (HR = 4.49 [95 % CI = 4.18–5.05]), or witness (HR = 9.56 [95 % CI = 7.19–12.69]) were associated with child protection services contact. Effect sizes were similar for boys and girls. Early interventions that specifically aim to prevent early contact with the justice system among vulnerable children and their families involved with child protection services are required. [ABSTRACT FROM AUTHOR]

We used a psychophysiological marker of visual attention (the visual scanpath) to investigate the effects of atypical (risperidone) vs. typical (haloperidol) antipsychotic medication on facial emotion perception in schizophrenia (n=28) and healthy control (n=28) groups. Of the schizophrenia subjects, 15 were prescribed risperidone. Visual scanpaths to ‘happy’, ‘sad’ and ‘neutral’ faces were recorded using video-oculography, and concurrent emotion-recognition accuracy was assessed using multiple-option tasks. Compared to control subjects, both schizophrenia subgroups showed a restriction in visual scanning (reduced total fixation number and decreased scanpath length). Haloperidol-treated schizophrenia subjects exhibited an additional and consistent pattern of reduced attention (fixation) to salient features for neutral and happy. By contrast, risperidone-treated subjects showed a relatively greater attention to salient features for these expressions, in which they did not differ from controls. Recognition accuracy for happy and neutral showed a similar lack of impairment. These findings suggest that risperidone may play a specific role in schizophrenia in the ability to attend to salient features, and to integrate this information into an accurate percept for neutral and positive expressions in particular. [Copyright &y& Elsevier]

Childhood maltreatment is associated with early childhood developmental vulnerabilities. However, the extent to which higher levels of child protection responses confer benefit to developmental competencies, and the impact of earlier timing of first reports in relation to early childhood vulnerability remains unclear. We examined associations between early developmental vulnerabilities and (1) the highest level of child protection response (where OOHC was deemed the highest response among other types of reports/responses), and (2) the developmental timing of the first child protection report. Participants included 67,027 children from the New South Wales Child Development Study, of whom 10,944 were reported to child protection services up to age 5 years. A series of Multinomial Logistic Regressions were conducted to examine focal associations. Children with substantiated maltreatment reports showed the strongest odds of vulnerability on three or more developmental domains (adjusted OR = 4.90; 95% CI = 4.13–5.80); children placed in OOHC showed slightly better physical, cognitive and communication competencies (adjusted ORs from 1.83 to 2.65) than those with substantiated reports that did not result in OOHC placements (adjusted OR from 2.77 to 3.67), when each group was compared to children with no child protection reports. Children with first maltreatment reports occurring in the first 18 months of life showed the strongest likelihood of developmental vulnerabilities on three or more developmental domains (adjusted OR = 3.56; 95% CI = 3.15–4.01) relative to children with no child protection reports. Earlier reports of maltreatment may signal the need for targeted remediation of early developmental competencies to mitigate early developmental difficulties. [ABSTRACT FROM AUTHOR]

Highlights • Associations are repeatedly found in NR3C1 for stress-related psychopathology. • NR3C1 methylation in relation to psychopathology/trauma is inconsistent. • Methodological variability likely impacts consistency of results across studies. • Inverse associations between NR3C1 methylation and expression have been reported. • No associations between NR3C1 genetic variants and NR3C1 methylation are evident. Abstract The glucocorticoid receptor gene (NR3C1) is a critical component of the stress response system. Cytosine methylation of NR3C1 has been repeatedly associated with trauma and mental disorders, including major depression, post-traumatic stress disorder, anxiety, and personality disorders, suggesting that NR3C1 methylation may play a role in stress-related psychopathology. We systematically reviewed 55 studies examining NR3C1 DNA methylation in association with trauma exposure, psychopathology, gene expression, and/or common genetic variants. Overall, a number of NR3C1 CpG sites were significantly associated with trauma or psychopathology, but significant findings were often inconsistent across studies. This lack of consistency is likely influenced by significant methodological variability - experimentally and analytically - across studies. Selected common genetic variants show no significant effect on NR3C1 CpG methylation. In contrast, there was ample evidence linking increased methylation of NR3C1 to reduced expression of this gene. The inverse association between methylation and gene expression shown across eight out of ten studies supports the notion that methylation in the promoter region of NR3C1 is associated with transcriptional silencing. [ABSTRACT FROM AUTHOR]

Background The single nucleotide polymorphism (SNP) rs1344706 [A > C] within intron 2 of the zinc finger protein 804A gene ( ZNF804A ) is associated with schizophrenia at the genome-wide level, but its function in relation to the development of psychotic disorders, including its influence on brain morphology remains unclear. Methods Using both univariate (voxel-based morphometry, VBM; cortical thickness) and multivariate (source-based morphometry, SBM) approaches, we examined the effects of variation of the rs1344706 polymorphism on grey matter integrity in 214 Caucasian schizophrenia cases and 94 Caucasian healthy individuals selected from the Australian Schizophrenia Research Bank. Results Neither univariate nor multivariate analyses showed any associations between indices of grey matter and rs1344706 variation in schizophrenia or healthy participants. This was revealed in the context of the typical pattern of decreased grey matter integrity in schizophrenia compared to healthy individuals, including: (1) large grey matter volume reductions in the orbitofrontal and anterior cingulate cortices and the left fusiform/inferior temporal gyri; (2) decreased cortical thickness in the left inferior temporal and fusiform gyri, the left orbitofrontal gyrus, as well as in the right pars opercularis/precentral gyrus; and (3) decreased covariation of grey matter concentration in frontal and limbic brain regions emerging from the SBM analyses. Conclusions Contrary to some – but not all – previous findings, this study of a large sample of schizophrenia cases and healthy controls reveals no evidence for association between grey matter alterations and variation in rs1344706 ( ZNF804A ). Differences in sample sizes and ethnicities may account for discrepant findings between the present and previous studies. [ABSTRACT FROM AUTHOR]

Children in out-of-home care (OOHC) are generally at increased risk of health and social adversities compared to their peers. However, the experiences of children in OOHC are not uniform and their associated health and social indices may vary in relation to characteristics of OOHC placements and child protection contact. To examine associations between a range of characteristics of OOHC placements and child protection contact (e.g., number, type, and age of placement) with educational underachievement, mental disorder, and police contact (as a victim, witness, or person of interest) in childhood. Participants were Australian children drawn from the New South Wales Child Development Study cohort who had been placed in OOHC at least once between the ages of 0–13 years (n = 2082). Logistic regression was used to examine prospective associations of OOHC placement and child protection contact characteristics (type of carer, placement instability, duration and frequency of maltreatment, and amount of time in care) with educational underachievement, mental disorder diagnosis and any type of police contact. Placements with foster carers, greater placement instability, longer and more frequent exposure to maltreatment, and longer time spent in care were each associated with greater likelihood of consequences in all domains of functioning. Children with certain placement characteristics are at higher risk of adverse consequences and should be prioritised for support services. The magnitude of relationships was not uniform across different health and social indices, highlighting the need for holistic, multiagency approaches to support children placed in care. [ABSTRACT FROM AUTHOR]

Markers of HPA axis function, including diurnal cortisol rhythm and cortisol responses to stress or pharmacological manipulation, are increasingly reported as disrupted in schizophrenia (SZ) and bipolar disorder (BD). However, there has been no direct comparison of cortisol responses to stress in SZ and BD in the same study, and associations between cortisol dysfunction and illness characteristics remain unclear. In this study we used spline embedded linear mixed models to examine cortisol levels of SZ and BD participants at waking, during the first 45 min after waking (representing the cortisol awakening response; CAR), during the period of rapid cortisol decline post the awakening response, and in reaction to a stressor (MRI scan), relative to healthy controls (HC). Contrary to expectations, neither SZ nor BD showed differences in waking cortisol levels, CAR, or immediate post-CAR decline compared to HC; however, waking cortisol levels were greater in BD relative to SZ. In response to the MRI stressor, the SZ group showed a significant absence of the expected increase in cortisol responsivity to stress, which was seen in both the BD and HC groups. Clinical factors affecting the CAR differed between SZ and BD. In SZ, higher antipsychotic medication dosage was associated with a steeper incline of the CAR, while greater positive symptom severity was associated with a more blunted CAR, and greater levels of anxiety were associated with the blunted cortisol response to stress. In BD, longer illness duration was associated with a steeper incline in CAR and lower levels of waking cortisol. These results suggest that cortisol responses may normalize with medication (in SZ) and longer illness duration (in BD), in line with findings of aberrant cortisol levels in the early stages of psychotic disorders. [ABSTRACT FROM AUTHOR]

Recent evidence shows that genetic and environmental risk factors for psychotic disorders are associated with higher levels of schizotypy (or psychosis proneness) in the general population. However, little is known about how these risk factors interact. We specifically examined whether genetic loading for schizophrenia moderates the association between childhood trauma severity and schizotypy. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and childhood trauma severity was measured with the Childhood Trauma Questionnaire (CTQ) among a total of 168 participants (comprising 51 healthy individuals, 56 diagnosed with schizophrenia, and 61 with bipolar disorder). Polygenic risk scores (PRS) for schizophrenia were calculated for all participants and examined as a potential moderator of associations between total scores on the CTQ and schizotypy total scores and dimensions (i.e., cognitive-perceptual, interpersonal, disorganised). Multiple linear regression models revealed associations between childhood trauma and all dimensions of schizotypy, but no associations between PRS and schizotypy. A significant interaction between PRS and childhood trauma was evident for the interpersonal and disorganised dimensions of schizotypy, as well as the total score, reflecting positive associations between childhood trauma severity and these two schizotypal dimensions, only for individuals with low or average PRS for schizophrenia. This suggests that trauma may be able to increase risk for psychosis independently of any genetic vulnerability. The present findings are consistent with the idea of several risk pathways for the development of psychotic disorders. • Trauma is associated with schizotypy only in people at low polygenic risk for schizophrenia. • Experiences of trauma may influence neurodevelopment independently of genetic vulnerability. • High levels of schizotypy are not dependent of high genetic loadings for schizophrenia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary Increased peripheral levels of morning cortisol have been reported in people with schizophrenia (SZ) and bipolar disorder (BD), but findings are inconsistent and few studies have conducted direct comparisons of these disorders. We undertook a meta-analysis of studies examining single measures of morning cortisol (before 10 a.m.) levels in SZ or BD, compared to controls, and to each other; we also sought to examine likely moderators of any observed effects by clinical and demographic variables. Included studies were obtained via systematic searches conducted using Medline, BIOSIS Previews and Embase databases, as well as hand searching. The decision to include or exclude studies, data extraction and quality assessment was completed in duplicate by LG, SM and AS. The initial search revealed 1459 records. Subsequently, 914 were excluded on reading the abstract because they did not meet one or more of the inclusion criteria; of the remaining 545 studies screened in full, included studies were 44 comparing SZ with controls, 19 comparing BD with controls, and 7 studies directly comparing schizophrenia with bipolar disorder. Meta-analysis of SZ ( N = 2613, g = 0.387, p = 0.001) and BD ( N = 704, g = 0.269, p = 0.004) revealed moderate quality evidence of increased morning cortisol levels in each group compared to controls, but no difference between the two disorders ( N = 392, g = 0.038, p = 0.738). Subgroup analyses revealed greater effect sizes for schizophrenia samples with an established diagnosis (as opposed to ‘first-episode’), those that were free of medication, and those sampled in an inpatient setting (perhaps reflecting an acute illness phase). In BD, greater morning cortisol levels were found in outpatient and non-manic participants (as opposed to those in a manic state), relative to controls. Neither age nor sex affected cortisol levels in any group. However, earlier greater increases in SZ morning cortisol were evident in samples taken before 8 a.m. (relative to those taken after 8 a.m.). Multiple meta-regression showed that medication status was significantly associated with morning cortisol levels in SZ, when the effects of assay method, sampling time and illness stage were held constant. Heightened levels of morning cortisol in SZ and BD suggest long-term pathology of the hypothalamic-pituitary-adrenal (HPA) axis that may reflect a shared process of illness development in line with current stress-vulnerability models. [ABSTRACT FROM AUTHOR]

Abstract: Schizophrenia (SZ) and bipolar disorder (BD) exhibit common cognitive deficits that may impede the capacity for self-regulating affect. We examined the use of particular cognitive strategies for regulating negative affect in SZ and BD, and their associations with levels of mood symptomatology. Participants were 126 SZ, 97 BD, and 81 healthy controls (HC) who completed the Cognitive Emotion Regulation Questionnaire (CERQ), the Depression Anxiety Stress Scales (DASS) and the Hypomanic Personality Scale (HPS). Patients with SZ and BD reported more frequent rumination, catastrophising and self-blame, and less use of putting into perspective, relative to HC. Additionally, SZ patients were more likely to engage in other-blame, compared to HC. The most consistent predictors of symptomatology for SZ were self-blame and catastrophising, while for BD were rumination and reduced positive reappraisal. These findings demonstrate maladaptive use of cognitive strategies to self-regulate negative affect in SZ and BD, resembling those reported previously for unipolar depression. The ineffective use of adaptive cognitive reframing strategies in both patient groups may reflect the impact of their shared cognitive deficits, and requires further investigation. Remediation of cognitive capacities contributing to ineffective self-regulation may facilitate reduced mood symptomatology in SZ and BD. [Copyright &y& Elsevier]

Background: Volume reduction in insular cortex may constitute an important neuropathology in schizophrenia. We provide the first meta-analysis of studies that conducted region-of-interest analyses of the magnitude of effect and pattern of insula volume reduction in schizophrenia compared with healthy control subjects. Methods: Included studies examined insula volume in schizophrenia relative to healthy control subjects. Studies were located via electronic database searches and hand searching. Study selection, data extraction, and quality assessment were completed by two independent reviewers. Hedge''s g effect sizes were calculated using Comprehensive Meta-Analysis (v.2) to quantify volumetric differences between people with and without schizophrenia, accounting for moderating influences of age, sex, illness duration, medication, whole brain volume, and potential differences in hemispheric and anatomical subregions. Results: Random-effects analysis showed reductions of bilateral insula (n = 945, g = −.446, 95% confidence interval −.639 to −.252, p = .00001), with moderate heterogeneity apparent (I2 = 76%). This effect was consistent across left and right insula and not influenced by illness stage or sex. Additional analyses revealed larger reductions of anterior (n = 605, g = −.643, p < 0.001; I2 = 52%) than of posterior insula (n = 453, g = −.321, p = .028; I2 = 55%). Meta-regression analyses did not identify any significant predictors of reduced insula volume. Conclusions: This meta-analysis indicates medium-sized reduction of insula volume in schizophrenia, of greatest magnitude in the anterior subregion. Cellular distinctions across anterior and posterior insula may contribute to understanding the neuropathology and functional significance of the observed volumetric differences. [Copyright &y& Elsevier]

Abstract: Background: The large quantity of systematic reviews of magnetic resonance imaging studies in schizophrenia challenges their meaningful interpretation. This meta-review synthesises the available information from systematic reviews of structural alteration in both chronic and first-episode schizophrenia. Methods: Systematic reviews were identified using electronic databases. Review methodological quality was assessed according to the Assessment of Multiple Systematic Reviews checklist. Data were extracted in duplicate and quality assessed for consistency and precision, guided by Grading of Recommendations Assessment, Development and Evaluation recommendations. Results: Integration of volumetric and voxel-based estimates allowed critical assessment of the magnitude and location of anatomical differences. There is evidence for grey matter reductions of anterior cingulate, frontal (particularly medial and inferior) and temporal lobes, hippocampus/amygdala, thalamus, and insula that may be magnified over time. Other regional alterations appear specific to illness stage or medication status. Conclusions: There is limited high quality evidence supporting grey or white matter changes in schizophrenia, which has previously been obscured by a large volume of conflicting lower quality evidence. [Copyright &y& Elsevier]