Patients with schizophrenia spectrum disorders (SSD) tend to lack insight, which is linked to poor outcomes. The effect size of previous treatments on insight changes in SSD has been small. Metacognitive interventions may improve insight in SSD, although this remains unproved.

We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the effects of metacognitive interventions designed for SSD, namely Metacognitive Training (MCT) and Metacognitive Reflection and Insight Therapy (MERIT), on changes in cognitive and clinical insight at post-treatment and at follow-up.

Twelve RCTs, including 10 MCT RCTs (n = 717 participants) and two MERIT trials (n = 90), were selected, totalling N = 807 participants. Regarding cognitive insight six RCTs (n = 443) highlighted a medium effect of MCT on self-reflectiveness at post-treatment, d = 0.46, p < 0.01, and at follow-up, d = 0.30, p < 0.01. There was a small effect of MCT on self-certainty at post-treatment, d = −0.23, p = 0.03, but not at follow-up. MCT was superior to controls on an overall Composite Index of cognitive insight at post-treatment, d = 1.11, p < 0.01, and at follow-up, d = 0.86, p = 0.03, although we found evidence of heterogeneity. Of five MCT trials on clinical insight (n = 244 participants), which could not be meta-analysed, four of them favoured MCT compared v. control. The two MERIT trials reported conflicting results.

Metacognitive interventions, particularly Metacognitive Training, appear to improve insight in patients with SSD, especially cognitive insight shortly after treatment. Further long-term RCTs are needed to establish whether these metacognitive interventions-related insight changes are sustained over a longer time period and result in better outcomes.

Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk.

Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups.

Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1–4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79–88%).

These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.

Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.

In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).

MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.

Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.

Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity.

We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators.

Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data.

Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.

Schizotypy, a putative schizophrenia endophenotype, has been associated with brain-structural variations partly overlapping with those in psychotic disorders. Variations in precuneus structure have been repeatedly reported, whereas the involvement of fronto-striatal networks – as in schizophrenia – is less clear. While shared genetic architecture is thought to increase vulnerability to environmental insults, beneficial factors like general intelligence might buffer their effect.

To further investigate the role of fronto-striatal networks in schizotypy, we examined the relationship of voxel- and surface-based brain morphometry and a measure of schizotypal traits (Schizotypal Personality Questionnaire, with subscores Cognitive-Perceptual, Interpersonal, Disorganised) in 115 healthy participants [54 female, mean age (s.d.) = 27.57(8.02)]. We tested intelligence (MWT-B) as a potential moderator.

We found a positive association of SPQ Cognitive-Perceptual with putamen volume (p = 0.040, FWE peak level-corrected), moderated by intelligence: with increasing IQ, the correlation of SPQ Cognitive-Perceptual and striatal volume decreased (p = 0.022). SPQ Disorganised was positively correlated with precentral volume (p = 0.013, FWE peak level-corrected). In an exploratory analysis (p < 0.001, uncorrected), SPQ total score was positively associated with gyrification in the precuneus and postcentral gyrus, and SPQ Disorganised was negatively associated with gyrification in the inferior frontal gyrus.

Our findings support the role of fronto-striatal networks for schizotypal features in healthy individuals, and suggest that these are influenced by buffering factors like intelligence. We conclude that protective factors, like general cognitive capacity, might attenuate the psychosis risk associated with schizotypy. These results endorse the idea of a continuous nature of schizotypy, mirroring similar findings in schizophrenia.

As new cannabis products and administration methods proliferate, patterns of use are becoming increasingly heterogeneous. However, few studies have explored different profiles of cannabis use and their association with problematic use.

Latent class analysis (LCA) was used to identify subgroups of past-year cannabis users endorsing distinct patterns of use from a large international sample (n = 55 240). Past-12-months use of six different cannabis types (sinsemilla, herbal, hashish, concentrates, kief, edibles) were used as latent class indicators. Participants also reported the frequency and amount of cannabis used, whether they had ever received a mental health disorder diagnosis and their cannabis dependence severity via the Severity of Dependence Scale (SDS).

LCA identified seven distinct classes of cannabis use, characterised by high probabilities of using: sinsemilla & herbal (30.3% of the sample); sinsemilla, herbal & hashish (20.4%); herbal (18.4%); hashish & herbal (18.8%); all types (5.7%); edibles & herbal (4.6%) and concentrates & sinsemilla (1.7%). Relative to the herbal class, classes characterised by sinsemilla and/or hashish use had increased dependence severity. By contrast, the classes characterised by concentrates use did not show strong associations with cannabis dependence but reported greater rates of ever receiving a mental health disorder diagnosis.

The identification of these distinct classes underscores heterogeneity among cannabis use behaviours and provides novel insight into their different associations with addiction and mental health.

The promise of precision medicine for autism spectrum disorder (ASD) hinges on developing neuroscience-informed individualized interventions. Taking an important step in this direction, we investigated neuroplasticity in response to an ecologically-valid, computer-based social-cognitive training (SCOTT).

In an active control group design, 48 adults with ASD were randomly assigned to a 3-month SCOTT or non-social computer training. Participants completed behavioral tasks, a functional and structural magnetic resonance imaging session before and after the training period.

The SCOTT group showed social-cognitive improvements on close and distant generalization tasks. The improvements scaled with reductions in functional activity and increases in cortical thickness in prefrontal regions.

In sum, we provide evidence for the sensitivity of neuroscientific methods to reflect training-induced social-cognitive improvements in adults with ASD. These results encourage the use of neuroimaging data to describe and quantify treatment-related changes more broadly.

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.

An ongoing challenge in understanding and treating personality disorders (PDs) is a significant heterogeneity in disorder expression, stemming from variability in underlying dynamic processes. These processes are commonly discussed in clinical settings, but are rarely empirically studied due to their personalized, temporal nature. The goal of the current study was to combine intensive longitudinal data collection with person-specific temporal network models to produce individualized symptom-level structures of personality pathology. These structures were then linked to traditional PD diagnoses and stress (to index daily functioning).

Using about 100 daily assessments of internalizing and externalizing domains underlying PDs (i.e. negative affect, detachment, impulsivity, hostility), a temporal network mapping approach (i.e. group iterative multiple model estimation) was used to create person-specific networks of the temporal relations among domains for 91 individuals (62.6% female) with a PD. Network characteristics were then associated with traditional PD symptomatology (controlling for mean domain levels) and with daily variation in clinically-relevant phenomena (i.e. stress).

Features of the person-specific networks predicted paranoid, borderline, narcissistic, and obsessive-PD symptom counts above average levels of the domains, in ways that align with clinical conceptualizations. They also predicted between-person variation in stress across days.

Relations among behavioral domains thought to underlie heterogeneity in PDs were indeed associated with traditional diagnostic constructs and with daily functioning (i.e. stress) in person-specific networks. Findings highlight the importance of leveraging data and models that capture person-specific, dynamic processes, and suggest that person-specific networks may have implications for precision medicine.

Childhood adversities have been associated with chronic inflammation and risk for cardiovascular disease. With some exceptions, existing knowledge of this relationship is based on retrospective self-reports, potentially subject to recall bias or memory problems. We seek to determine whether childhood maltreatment is associated with higher C-reactive protein (CRP) later in life and whether individuals with official and retrospective self-reports of maltreatment and men and women show similar increases in risk.

Data are from in-person interviews in 2009–2010 with 443 offspring (mean age = 23.4) of parents in a longitudinal study of the consequences of childhood maltreatment. Official reports of maltreatment were abstracted from 2011–2013 Child Protective Services records. Eleven measures were used to assess self-reported maltreatment retrospectively. Seventeen percent of offspring had official reports, whereas self-reported prevalence rates ranged from 5.4% to 64.8%. CRP was assessed through blood spot samples. Regression models were used to estimate the effect of maltreatment on inflammation, adjusting for age, sex, race, parent occupational status, current depression, smoking, and heavy drinking.

Individuals with official reports of child maltreatment and, specifically, physical abuse, had significantly higher levels of CRP than non-maltreated individuals. Maltreated females showed elevated CRP, independent of control variables, whereas no significant association was observed in males. Retrospective self-report measures of child maltreatment did not predict elevated CRP.

Individuals with documented histories of childhood maltreatment are at increased risk for chronic inflammation and may benefit from targeted interventions. The results strengthen inferences about the effects of childhood maltreatment on inflammation in females.

Pregnant women require increased levels of n-3 polyunsaturated fatty acids (PUFAs) due to the demands of the growing fetus. Although some evidence indicates that maternal intake of fish and n-3 PUFAs is associated with reduced risk of postpartum depression, the results are inconsistent.

We investigated whether dietary consumption of fish and/or n-3 PUFAs during pregnancy is associated with a reduced risk of maternal postpartum depression at 6 months after delivery and of serious mental illness at 1 year in a Japanese population. After exclusion and multiple imputation from a dataset comprising 103 062 pregnancies obtained in the Japan Environment and Children's Study, we evaluated 84 181 and 81 924 women at 6 months and 1 year after delivery, respectively.

Multivariable logistic regression showed a reduced risk of postpartum depression at 6 months in the second to fifth quintiles v. the lowest quintile for fish and n-3 PUFA intake, with trend tests also revealing a significant linear association. At 1 year after delivery, fish intake was associated with a reduced risk of serious mental illness in the second to fifth quintiles v. the lowest quintile for fish and in the third to fifth quintiles v. the lowest quintile for n-3 PUFA intake, with trend tests also revealing a significant linear association.

Women with higher fish and/or n-3 PUFA intake showed reduced risk of postpartum depression at 6 months after delivery and of serious mental illness at 1 year after delivery.

The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation.

In a randomized, controlled trial, 271 mid-life adults (30–54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes.

Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology.

In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.

Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).

We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.

There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.

These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.

Retrospectively recalled adverse childhood experiences (ACEs) are associated with adult mood problems, but evidence from prospective population cohorts is limited. The aims of this study were to test links between prospectively ascertained ACEs and adult mood problems up to age 50, to examine the role of child mental health in accounting for observed associations, and to test gender differences in associations.

The National Child Development Study is a UK population cohort of children born in 1958. ACEs were defined using parent or teacher reports of family adversity (parental separation, child taken into care, parental neglect, family mental health service use, alcoholism and criminality) at ages 7–16. Children with no known (n = 9168), single (n = 2488) and multiple (n = 897) ACEs were identified in childhood. Adult mood problems were assessed using the Malaise inventory at ages 23, 33, 42 and 50 years. Associations were examined separately for males and females.

Experiencing single or multiple ACEs was associated with increased rates of adult mood problems after adjustment for childhood psychopathology and confounders at birth [2+ v. 0 ACEs – men: age 23: odds ratio (OR) 2.36 (95% confidence interval (CI) 1.7–3.3); age 33: OR 2.40 (1.7–3.4); age 42: OR 1.85 (1.4–2.4); age 50: OR 2.63 (2.0–3.5); women: age 23: OR 2.00 (95% CI 1.5–2.6); age 33: OR 1.81 (1.3–2.5); age 42: OR 1.59 (1.2–2.1); age 50: OR 1.32 (1.0–1.7)].

Children exposed to ACEs are at elevated risk for adult mood problems and a priority for early prevention irrespective of the presence of psychopathology in childhood.

The literature on psychosis-relevant outcomes in cannabis users does not adequately address the confounding effects of other substance use/misuse and psychiatric disorders.

We studied a unique population for whom cannabis use is central and necessary to their way of life. They are forbidden from using other substances, including tobacco and alcohol. Their use of cannabis is heavy, chronic, and begins early. The cases were compared with matched controls who did not use cannabis, alcohol, or drugs. The controls were from the same location and shared similar beliefs and lifestyle, except for cannabis use. Attenuated psychosis-relevant phenomena were assessed with the Schizotypal Personality Questionnaire (SPQ) and cognitive functioning with a culture-neutral computerized cognitive battery.

Fifteen cases and 12 matched controls were studied. The cases averaged >30 000 lifetime cannabis exposures. Relative to controls, the cases had significantly higher mean (s.d.) SPQ scores 24 (14.32) v. 13 (8.92), p = 0.031; and poorer cognitive performance, reflected by a lower mean (s.d.) composite cognitive score −0.23 (0.32) v. +0.28 (0.52), p = 0.03. Moderate to large effect sizes were noted for differences in tests of attention, psychomotor speed, working memory, cognitive flexibility, visuo-spatial processing, and verbal memory. A subsample of cases had higher SPQ scores and worse cognitive performance than their siblings not using cannabis.

Heavy, chronic, and early cannabis use that is not confounded by other drug use is associated with psychosis-relevant phenomena and cognitive deficits. The findings are relevant to the evolving attitudes and laws about cannabis.