Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis.

A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition.

We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains.

Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).

Virtual reality exposure therapy (VRET) is currently being used to treat social anxiety disorder (SAD); however, VRET's magnitude of efficacy, duration of efficacy, and impact on treatment discontinuation are still unclear.

We conducted a meta-analysis of studies that investigated the efficacy of VRET for SAD. The search strategy and analysis method are registered at PROSPERO (#CRD42019121097). Inclusion criteria were: (1) studies that targeted patients with SAD or related phobias; (2) studies where VRET was conducted for at least three sessions; (3) studies that included at least 10 participants. The primary outcome was social anxiety evaluation score change. Hedges' g and its 95% confidence intervals were calculated using random-effect models. The secondary outcome was the risk ratio for treatment discontinuation.

Twenty-two studies (n = 703) met the inclusion criteria and were analyzed. The efficacy of VRET for SAD was significant and continued over a long-term follow-up period: Hedges' g for effect size at post-intervention, −0.86 (−1.04 to −0.68); three months post-intervention, −1.03 (−1.35 to −0.72); 6 months post-intervention, −1.14 (−1.39 to −0.89); and 12 months post-intervention, −0.74 (−1.05 to −0.43). When compared to in vivo exposure, the efficacy of VRET was similar at post-intervention but became inferior at later follow-up points. Participant dropout rates showed no significant difference compared to in vivo exposure.

VRET is an acceptable treatment for SAD patients that has significant, long-lasting efficacy, although it is possible that during long-term follow-up, VRET efficacy lessens as compared to in vivo exposure.

Although efficacious treatments for major depression are available, efficacy is suboptimal and recurrence is common. Effective preventive strategies could reduce disability associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel and safe intervention that attenuates biases associated with depression. This study investigated whether the delivery of a CBM programme designed to attenuate negative cognitive biases over a period of 1 year would decrease the incidence of major depression among adults with subthreshold symptoms of depression.

Randomised double-blind controlled trial delivered an active CBM intervention or a control intervention over 52 weeks. Two hundred and two community-dwelling adults who reported subthreshold levels of depression were randomised (100 intervention, 102 control). The primary outcome of interest was the incidence of major depressive episode assessed at 11, 27 and 52 weeks. Secondary outcomes included onset of clinically significant symptoms of depression, change in severity of depression symptoms and change in cognitive biases.

Adherence to the interventions was modest though did not differ between conditions. Incidence of major depressive episodes was low. Conditions did not differ in the incidence of major depressive episodes. Likewise, conditions did not differ in the incidence of clinically significant levels of depression, change in the severity of depression symptoms or change in cognitive biases.

Active CBM intervention did not decrease the incidence of major depressive episodes as compared to a control intervention. However, adherence to the intervention programme was modest and the programme failed to modify the expected mechanism of action.

Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.

We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.

We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.

Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.

Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission.

Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM−, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM−, n = 80). Separate analyses in MDD participants who remitted were conducted.

DM+ had lower baseline global cognition, processing speed, and memory v. HM−, with no significant baseline differences amongst DM−, HM+, and HM− groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM−, scored significantly lower than HM− in working memory and processing speed.

Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.

Universal depression screening in youth typically focuses on strategies for identifying current distress and impairment. However, these protocols also play a critical role in primary prevention initiatives that depend on correctly estimating future depression risk. Thus, the present study aimed to identify the best screening approach for predicting depression onset in youth.

Two multi-wave longitudinal studies (N = 591, AgeM = 11.74; N = 348, AgeM = 12.56) were used as the ‘test’ and ‘validation’ datasets among youth who did not present with a history of clinical depression. Youth and caregivers completed inventories for depressive symptoms, adversity exposure (including maternal depression), social/academic impairment, cognitive vulnerabilities (rumination, dysfunctional attitudes, and negative cognitive style), and emotional predispositions (negative and positive affect) at baseline. Subsequently, multi-informant diagnostic interviews were completed every 6 months for 2 years.

Self-reported rumination, social/academic impairment, and negative affect best predicted first depression onsets in youth across both samples. Self- and parent-reported depressive symptoms did not consistently predict depression onset after controlling for other predictors. Youth with high scores on the three inventories were approximately twice as likely to experience a future first depressive episode compared to the sample average. Results suggested that one's likelihood of developing depression could be estimated based on subthreshold and threshold risk scores.

Most pediatric depression screening protocols assess current manifestations of depressive symptoms. Screening for prospective first onsets of depressive episodes can be better accomplished via an algorithm incorporating rumination, negative affect, and impairment.

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate neurodevelopmental disorders that are both characterized by difficulties in social cognition and social functioning. Due to methodological confounds, the degree of similarity in social cognitive impairments across these two disorders is currently unknown. This study therefore conducted a comprehensive comparison of social cognitive ability in ASD and SCZ to aid efforts to develop optimized treatment programs.

In total, 101 individuals with ASD, 92 individuals with SCZ or schizoaffective disorder, and 101 typically developing (TD) controls, all with measured intelligence in the normal range and a mean age of 25.47 years, completed a large battery of psychometrically validated social cognitive assessments spanning the domains of emotion recognition, social perception, mental state attribution, and attributional style.

Both ASD and SCZ performed worse than TD controls, and very few differences were evident between the two clinical groups, with effect sizes (Cohen's d) ranging from 0.01 to 0.34. For those effects that did reach statistical significance, such as greater hostility in the SCZ group, controlling for symptom severity rendered them non-significant, suggesting that clinical distinctions may underlie these social cognitive differences. Additionally, the strength of the relationship between neurocognitive and social cognitive performance was of similar, moderate size for ASD and SCZ.

Findings largely suggest comparable levels of social cognitive impairment in ASD and SCZ, which may support the use of existing social cognitive interventions across disorders. However, future work is needed to determine whether the mechanisms underlying these shared impairments are also similar or if these common behavioral profiles may emerge via different pathways.

Adolescence is a high-risk period for the onset of suicidal thoughts and behaviors. Identification of preceding patterns of internalizing and externalizing symptoms that are associated with subsequent suicidal thoughts may offer a better understanding of how to prevent adolescent suicide.

Data from the National Longitudinal Survey of Children and Youth, a prospective population-based Canadian cohort, contained Child Behavior Checklist items which were used to examine profiles and transitions of internalizing and externalizing symptoms in children, aged 6–11 years (n = 8266). The association between these profiles/transitions and suicidal thoughts in adolescents was examined using multivariate logistic regression modeling.

Latent profile analyses identified four measurement invariant profiles of internalizing and externalizing symptoms at ages 6/7 and 10/11: (1) low on all symptoms, (2) moderate on all symptoms, (3) high on all symptoms, and (4) high on hyperactivity/inattention and internalizing. Recurrent (homotypic or heterotypic) and increasing symptoms from 6/7 to 10/11 were associated with suicidal thoughts in adolescence, compared to those with stable low symptoms. Those with decreasing symptoms from 6/7 to 10/11 were not at increased risk of suicidal thought in adolescence.

While patterns of recurrent symptoms were associated with suicidal thoughts, a similar association was observed between profiles at age 10/11 years and suicidal thoughts. This suggests that the recent assessments of mental health symptoms in children may be as sufficient a predictor of adolescent suicidal thought as transition profiles.

Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use.

We performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects = 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk.

While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD.

These findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.

In 2010, an important earthquake devastated Haiti and caused thousands of deaths. In a social context where women are particularly vulnerable, this cross-sectional study examined the associations between sexual assaults experienced by women before the earthquake, the earthquake exposure, the traumatic consequences, and their satisfaction of social support received.

A total of 660 women aged 18 to 86 completed questionnaires assessing exposure to the earthquake, sexual assault victimization, peritraumatic distress, Posttraumatic stress disorder (PTSD), depression, and social support. A moderated moderation model was computed to examine associations between exposure to the earthquake, sexual assault, social support, and traumatic consequences.

Results showed that 31.06% of women were victims of sexual assault before the earthquake. They presented higher prevalence of peritraumatic distress, PTSD, and depression symptoms, compared to non-victims. The moderated-moderation model showed that sexual assault and exposure to the earthquake were positively associated with traumatic consequences (respectively, B = 0.560, p < 0.001; B = 0.196, p < 0.001), while social support was negatively associated with them (B = −0.095, p < 0.05). Results showed a triple interaction: women victim of sexual assault who were satisfied with received social support are less likely to develop traumatic consequences after being exposed to the earthquake(B = −0.141, p < 0.01).

By demonstrating the role of sexual assault in the development of mental health problems after the Haitian earthquake, this study shows the importance for clinicians to investigate interpersonal trauma experienced before or following natural disasters among survivors. Results also indicate the key role of family and communities to help survivors build resilience and coping strategies with their social support.

Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).

Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.

Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.

This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.

Outpatient interventions for adult anorexia nervosa typically have a modest impact on weight and eating disorder symptomatology. This study examined whether adding a brief online intervention focused on enhancing motivation to change and the development of a recovery identity (RecoveryMANTRA) would improve outcomes in adults with anorexia nervosa.

Participants with anorexia nervosa (n = 187) were recruited from 22 eating disorder outpatient services throughout the UK. They were randomised to receiving RecoveryMANTRA in addition to treatment as usual (TAU) (n = 99; experimental group) or TAU only (n = 88; control group). Outcomes were measured at end-of-intervention (6 weeks), 6 and 12 months.

Adherence rates to RecoveryMANTRA were 83% for the online guidance sessions and 77% for the use of self-help materials (workbook and/or short video clips). Group differences in body mass index at 6 weeks (primary outcome) were not significant. Group differences in eating disorder symptoms, psychological wellbeing and work and social adjustment (at 6 weeks and at follow-up) were not significant, except for a trend-level greater reduction in anxiety at 6 weeks in the RecoveryMANTRA group (p = 0.06). However, the RecoveryMANTRA group had significantly higher levels of confidence in own ability to change (p = 0.02) and alliance with the therapist at the outpatient service (p = 0.005) compared to the control group at 6 weeks.

Augmenting outpatient treatment for adult anorexia nervosa with a focus on recovery and motivation produced short-term reductions in anxiety and increased confidence to change and therapeutic alliance.

Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.

Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).

Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a ‘good’ response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36–3.41; I2 = 48.9) and ‘any’ response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35–3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on ‘any’ response (74.7% v. 65%; RR 1.15; 95% CI 0.82–1.62).

Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.

Psychoactive substance use is lower among married compared to divorced or unmarried men; yet, the nature of this effect remains unclear because becoming and staying married is potentially confounded with substance-related background familial and individual factors, like parental divorce and personality. The authors investigated the associations between marital status and substance use; how substance use changed across the transition to marriage; and whether marriage effects were likely to be causal.

The sample included 1790 adults from male–male twin pairs from a population-based registry. Measures of marital status and alcohol, tobacco, and cannabis use came from Life History Calendars. Data were analyzed using regression, co-twin comparison, and within-person models. The latter models are tools for quasi-causal inference that control for familial and individual-level confounders.

Married men used less alcohol, tobacco, and cannabis than men who were divorced/separated or single. In analyses of substance use across the transition to marriage, men reduced their alcohol and cannabis use both before and after marriage, but their tobacco use only after marriage. These effects were largely robust in co-twin and within-person analyses.

Marriage was associated with substantial reductions in substance use compared to being divorced/separated or single, and these reductions began prior to marriage. The co-twin comparison and within-person models ruled out the alternative explanation that marriage effects were due to confounding background familial and individual factors. These results provide strong evidence that the social role expectations associated with marriage reduce psychoactive substance use.