Although cognitive deficits in patients with schizophrenia are rooted early in development, the impact of psychosis on the course of cognitive functioning remains unclear. In this study a nested case-control design was used to examine the relationship between emerging psychosis and the course of cognition in individuals ascertained as clinical high-risk (CHR) who developed psychosis during the study (CHR + T).

Fifteen CHR + T subjects were administered a neurocognitive battery at baseline and post-psychosis onset (8.04 months, s.d. = 10.26). CHR + T subjects were matched on a case-by-case basis on age, gender, and time to retest with a group of healthy comparison subjects (CNTL, n = 15) and two groups of CHR subjects that did not transition: (1) subjects matched on medication treatment (i.e. antipsychotics and antidepressants) at both baseline and retesting (Meds-matched CHR + NT, n = 15); (2) subjects unmedicated at both assessments (Meds-free CHR + NT, n = 15).

At baseline, CHR + T subjects showed large global neurocognitive and intellectual impairments, along with specific impairments in processing speed, verbal memory, sustained attention, and executive function. These impairments persisted after psychosis onset and did not further deteriorate. In contrast, CHR + NT subjects demonstrated stable mild to no impairments in neurocognitive and intellectual performance, independent of medication treatment.

Cognition appears to be impaired prior to the emergence of psychotic symptoms, with no further deterioration associated with the onset of psychosis. Cognitive deficits represent trait risk markers, as opposed to state markers of disease status and may therefore serve as possible predictors of schizophrenia prior to the onset of the full illness.

Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas.

We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10–50 years) with BD (n = 39) and healthy volunteers (HV; n = 78). We identified brain regions with aberrant intrinsic functional connectivity in BD by first comparing voxel-wise mean global connectivity and then conducting correlation analyses. We used k-means clustering and multidimensional scaling to organize all detected regions into networks.

Across the brain, we detected areas of dysconnectivity in both youths and adults with BD relative to HV. There were no significant age-group × diagnosis interactions. When organized by interregional connectivity, the areas of dysconnectivity in patients with BD comprised two networks: one of temporal and parietal areas involved in late stages of visual processing, and one of corticostriatal areas involved in attention, cognitive control and response generation.

These data suggest that two networks show abnormal intrinsic functional connectivity in BD. Regions in these networks have been implicated previously in BD. We observed similar dysconnectivity in youths and adults with BD. These findings provide guidance for refining models of network-based dysfunction in BD.

Current theories and nosology assume that the self-evaluation (SE) of individuals with eating disorders (EDs) is unduly influenced by body shape and weight. However, experimental data supporting this link are scarce, and it is not specified which subdomains of SE might be affected.

We studied patients with anorexia nervosa (AN), bulimia nervosa (BN) and healthy controls (HC) with an affective priming (AP) procedure (Study 1) to unveil explicit and implicit associations between shape/weight and SE. We used weight/shape-related prime sentences, complemented by affectively congruent and incongruent target words from two SE domains. AP effects were assessed by event-related potentials (ERPs), reaction times (RTs) and subjective ratings. The ratings were also assessed (Study 2) in undergraduate restrained (RES) and unrestrained eaters (UNRES).

Study 1 demonstrated stronger AP effects in both ED groups compared to HC on RTs and subjective ratings. ERPs showed AP effects only in the BN group. Restrained eaters showed similar, albeit less pronounced, priming effects on subjective ratings.

ED patients associate shape/weight concerns with the non-appearance-related SE domains of interpersonal relationships and achievement/performance. These associations seem to be encoded deeper in BN patients relative to the other groups. Links between shape/weight and SE explain how body dissatisfaction impacts on self-esteem and mood in ED. The existence of similar associations in restrained eaters supports a continuum model according to which increasing associations between shape/weight and SE go along with increasing levels of ED symptoms.

Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes.

The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes.

Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP.

Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

Cannabis use disorder is associated with an earlier age at onset and a more severe outcome of schizophrenia spectrum disorders. The role of cannabis use before the onset of illness (premorbid cannabis use) has not been fully investigated. We here examined how amount and type of premorbid cannabis use was associated with the later course of illness including current substance use, symptoms and level of functioning in schizophrenia spectrum disorder.

We used a naturalistic sample of patients with DSM-IV schizophrenia spectrum disorders with a comprehensive history of illness and substance use. Data on premorbid substance use was obtained from comprehensive self-report. The relationship to outcome was investigated using regression models that included current substance use and premorbid functioning.

Pre-schizophrenia cannabis use was significantly associated with more severe psychotic symptoms and impaired functioning. Higher levels of premorbid cannabis use were associated with higher levels of current psychotic symptoms. These associations were independent of current substance use and premorbid functioning. Early use of cannabis (age <17 years) was associated with earlier age at onset of psychosis, independently of potential confounders.

Pre-psychosis cannabis use affects illness outcome in schizophrenia spectrum disorders, and is associated with lower age at onset of psychosis. These findings of independent negative effects of premorbid cannabis use in schizophrenia suggest that a limitation of the general use of cannabis may have beneficial health effects.

We investigated whether the predictive accuracy of mild cognitive impairment (MCI) for Alzheimer-type dementia (AD) in a clinical setting is dependent on age and the definition of MCI used.

Non-demented subjects older than 40 (n=320) who attended a memory clinic of a university hospital were reassessed 5 years later for the presence of AD. MCI was diagnosed according to the criteria of amnestic MCI, mild functional impairment (MFI), ageing-associated cognitive decline (AACD), and age-associated memory impairment (AAMI). The main outcome measure was the area under the curve (AUC) of a receiver operating characteristic (ROC) curve. Analyses were conducted on the entire sample and on subgroups of subjects aged 40–54, 55–69 and 70–85 years.

A diagnosis of AD at follow-up was made in 58 subjects. Four of them were in the 40–54 age group, 29 in the 55–69 age group and 25 in the 70–85 age group. The diagnostic accuracy in the entire sample was low to moderately high with AUCs ranging from 0.56 (AACD) to 0.75 (amnestic MCI). A good predictive accuracy with an AUC >0.80 was only observed in subjects aged 70–85 using the criteria of amnestic MCI (AUC=0.84).

The predictive accuracy of MCI for AD is dependent on age and the definition of MCI used. The predictive accuracy is good only for amnestic MCI in subjects 70–85 years. As subjects with prodromal AD are often younger than 70, the usefulness of MCI as predictor of AD in clinical practice is limited.

A basic phenomenological question of much theoretical and empirical interest is whether the latent structure of depression is dimensional or categorical in nature. Prior taxometric studies of youth depression have yielded mixed findings. In a step towards resolving these contradictory findings, the current taxometric investigation is the first to utilize a recently developed objective index, the comparison curve fit index, to evaluate the latent structure of major depression in an epidemiological sample of children and adolescents.

Data were derived from Mental Health of Children and Young People in Great Britain surveys. Participants were administered a structured diagnostic interview to assess for current depression. Parents (n = 683) were interviewed for children aged 5–16 years, and child interviews (n = 605) were conducted for those aged 11–16 years.

MAMBAC (mean above minus below a cut), MAXEIG (maximum eigenvalue) and L-Mode (latent mode) analyses provided convergent support for a dimensional latent structure.

The current findings suggest that depression in youth is more accurately conceptualized as a continuous syndrome rather than a discrete diagnostic entity.

Although aggressive (AGG) and non-aggressive rule-breaking (RB) dimensions of antisocial behavior have been shown to be differentially heritable, available studies have disagreed on the extent to which the genetic and environmental factors influencing AGG also influence RB. The current meta-analysis sought to clarify the extent of etiological overlap between AGG and RB.

Thirteen twin/sibling studies examining the covariation between AGG and RB were collected, of which 11 (with 12 independent samples) were ultimately included in the analyses (n=12923 twin/sibling pairs). Genetic and environmental correlations between AGG and RB served as study effect sizes. When squared, these correlations directly index the proportion of genetic and environmental overlap. Data were analyzed using mixed effect models.

Analyses revealed that genetic influences on AGG were largely, but not entirely, distinct from those on RB: only 38.4% of the genetic influences on AGG overlapped with those on RB. Similarly, only 10.2% of the non-shared environmental influences on AGG overlapped with those on RB. Although the conclusion that etiological influences on AGG are partially distinct from those on RB persisted across several potential moderators, the age of the sample and the informant used were found to moderate the extent of overlap.

The findings underscore the presence of meaningful etiological distinctions between AGG and RB, and imply that future conceptualizations of antisocial behavior should be organized (at least in part) around the dimensions of AGG and RB.

Neurocognitive and social cognitive impairments represent important treatment targets in schizophrenia, as they are significant predictors of functional outcome. Different rehabilitative interventions have recently been developed, addressing both cognitive and psychosocial domains. Although promising, results are still heterogeneous and predictors of treatment outcome are not yet identified. In this study we evaluated the efficacy of two newly developed social cognitive interventions, respectively based on the use of videotaped material and comic strips, combined with domain-specific Cognitive Remediation Therapy (CRT). We also analysed possible predictors of training outcome, including basal neurocognitive performance, the degree of cognitive improvement after CRT and psychopathological variables.

Seventy-five patients with schizophrenia treated with CRT, were randomly assigned to: social cognitive training (SCT) group, Theory of Mind Intervention (ToMI) group, and active control group (ACG).

ANOVAs showed that SCT and ToMI groups improved significantly in ToM measures, whereas the ACG did not. We reported no influences of neuropsychological measures and improvement after CRT on changes in ToM. Both paranoid and non-paranoid subjects improved significantly after ToMI and SCT, without differences between groups, despite the better performance in basal ToM found among paranoid patients. In the ACG only non-paranoid patients showed an improvement in non-verbal ToM.

Results showed that both ToMI and SCT are effective in improving ToM in schizophrenia with no influence of neuropsychological domains. Our data also suggest that paranoid symptoms may discriminate between different types of ToM difficulties in schizophrenia.

The aetiological pathways to borderline personality disorder (BPD) remain only partly elucidated. Retrospective research indicates that prenatal adversity may be an important early risk factor in the development of BPD. This requires corroboration with prospective longitudinal studies.

A community sample of 6050 mothers and their children (born between April 1991 and December 1992) were assessed. Maternal anxiety and depression and maternal alcohol and tobacco consumption were assessed during pregnancy (18 and 32 weeks gestation). Postnatal risks, including maladaptive parenting (suboptimal parenting and parent conflict), family adversity, maternal anxiety and depression and maternal alcohol and tobacco consumption, were assessed during early childhood. Internalizing and externalizing symptoms were assessed in late childhood. Trained psychologists interviewed children in late childhood to ascertain the presence of BPD (at least five probable/definite symptoms).

In unadjusted analyses, all prenatal risk factors (i.e. maternal alcohol and tobacco consumption and maternal anxiety and depression) were significantly associated with BPD. Following adjustment for sex, birthweight and postnatal exposure to anxiety and depression respectively, maladaptive parenting, family adversity and child's internalizing and externalizing symptoms, prenatal anxiety at 18 weeks gestation [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.18–2.09] and depression at 18 weeks (OR 1.59, 95% CI 1.08–2.32) and 32 weeks (OR 1.57, 95% CI 1.14–2.18) gestation remained significantly associated with BPD.

This study provides prospective evidence of associations between prenatal adversities and BPD at 11–12 years. Prenatal anxiety and depression were independently associated with BPD, suggesting that they may exert direct effects on BPD during the prenatal period. This highlights the importance of programmes to reduce maternal stress during pregnancy.

Different theories of the link between socio-economic status (SES) and mental illness have been postulated. In particular, two theories of this association, social causation and social selection, differ in the implied causal pathway. The authors employ behavior genetic modeling to consider evidence for both social selection and social causation in the relationship between income variation and internalizing disorders.

Behavior genetic modeling was used to estimate the presence of gene–environment interaction (GxE, social causation) in the presence of gene–environment correlation (rGE, social selection). Participants were members of a sample of 719 twin pairs from the Midlife in the United States study. Four internalizing (INT) syndromes were assessed: major depression (MD); generalized anxiety disorder (GAD); panic attacks (PA); neuroticism (N). SES was measured with total family household income.

One factor best accounted for the variance shared between MD, GAD, PA and N. The etiology of variation in INT changed from high to low levels of income, with unique environmental factors playing a larger role in INT variation at lower levels of income. Across levels of income, rGE between income and INT was modest (low income ra=0.39 to high income ra=0.54), implying a selection process operating through genetic effects linking lower income with INT psychopathology.

Findings support social causation by suggesting that low income contributes significantly to environmental variation in INT. Modest support was found for social selection, but should be extended using longitudinal designs. Effective interventions for internalizing psychopathology may differ depending on income.

Depression is a clinically heterogeneous disorder. Previous large-scale genetic studies of depression have explored genetic risk factors of depression case–control status or aggregated sums of depressive symptoms, ignoring possible clinical or genetic heterogeneity.

We analyse data from 148 752 subjects of white British ancestry in the UK Biobank who completed nine items of a self-rated measure of current depressive symptoms: the Patient Health Questionnaire (PHQ-9). Genome-Wide Association analyses were conducted for nine symptoms and two composite measures. LD Score Regression was used to calculate SNP-based heritability (h2SNP) and genetic correlations (rg) across symptoms and to investigate genetic correlations with 25 external phenotypes. Genomic structural equation modelling was used to test the genetic factor structure across the nine symptoms.

We identified nine genome-wide significant genomic loci (8 novel), with no overlap in loci across symptoms. h2SNP ranged from 6% (concentration problems) to 9% (appetite changes). Genetic correlations ranged from 0.54 to 0.96 (all p < 1.39 × 10−3) with 30 of 36 correlations being significantly smaller than one. A two-factor model provided the best fit to the genetic covariance matrix, with factors representing ‘psychological’ and ‘somatic’ symptoms. The genetic correlations with external phenotypes showed large variation across the nine symptoms.

Patterns of SNP associations and genetic correlations differ across the nine symptoms, suggesting that current depressive symptoms are genetically heterogeneous. Our study highlights the value of symptom-level analyses in understanding the genetic architecture of a psychiatric trait. Future studies should investigate whether genetic heterogeneity is recapitulated in clinical symptoms of major depression.