Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration.

Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates.

Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates.

Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice.

Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.

Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.

HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.

Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Using a longitudinal twin design and a latent growth curve/autoregressive approach, this study examined the genetic–environmental architecture of substance use across adolescence.

Self-reports of substance use (i.e. alcohol, marijuana) were collected at ages 13, 14, 15, and 17 years from 476 twin pairs (475 boys, 477 girls) living in the Province of Quebec, Canada. Substance use increased linearly across the adolescent years.

ACE modeling revealed that genetic, as well as shared and non-shared environmental factors explained the overall level of substance use and that these same factors also partly accounted for growth in substance use from age 13 to 17. Additional genetic factors predicted the growth in substance use. Finally, autoregressive effects revealed age-specific non-shared environmental influences and, to a lesser degree, age-specific genetic influences, which together accounted for the stability of substance use across adolescence.

The results support and expand the notion that genetic and environmental influences on substance use during adolescence are both developmentally stable and developmentally dynamic.

The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines.

The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD.

Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays.

There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (β = 0.31, t = 2.41, p = 0.025).

Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.

Attenuated inhibitory control is one of the most robust findings in the neuropsychology of attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether this represents a deficit in outright stopping (reactive inhibition), whether it relates to a deficit in anticipatory response slowing (proactive inhibition), or both. In addition, children with other development disorders, such as autism spectrum disorder (ASD), often have symptoms of inattention, impulsivity, and hyperactivity similar to children with ADHD. These may relate to similar underlying changes in inhibitory processing.

In this study, we used a modified stop-signal task to dissociate reactive and proactive inhibition. We included not only children with ADHD, but also children primarily diagnosed with an ASD and high parent-rated levels of ADHD symptoms.

We replicated the well-documented finding of attenuated reactive inhibition in children with ADHD. In addition, we found a similar deficit in children with ASD and a similar level of ADHD symptoms. In contrast, we found no evidence for deficits in proactive inhibition in either clinical group.

These findings re-emphasize the role of reactive inhibition in children with ADHD and ADHD symptoms. Moreover, our findings stress the importance of a trans-diagnostic approach to the relationship between behavior and neuropsychology.

Day hospital mentalization-based treatment (MBT-DH) is a promising treatment for borderline personality disorder (BPD) but its evidence base is still limited. This multi-site randomized trial compared the efficacy of MBT-DH delivered by a newly set-up service v. specialist treatment as usual (S-TAU) tailored to the individual needs of patients, and offered by a well-established treatment service.

Two mental healthcare institutes in The Netherlands participated in the study. Patients who met DSM-IV criteria for BPD and had a score of ⩾20 on the borderline personality disorder severity index (BPDSI) were randomly allocated to MBT-DH (N = 54) or S-TAU (N = 41). The primary outcome variable was the total score on the BPDSI. Secondary outcome variables included symptom severity, quality of life, and interpersonal functioning. Data were collected at baseline and every 6 months until 18-month follow-up, and were analyzed using multilevel analyses based on intention-to-treat principles.

Both treatments were associated with significant improvements in all outcome variables. MBT-DH was not superior to S-TAU on any outcome variable. MBT-DH was associated with higher acceptability in BPD patients compared v. S-TAU, reflected in significantly higher early drop-out rates in S-TAU (34%) v. MBT-DH (9%).

MBT-DH delivered by a newly set-up service is as effective as specialist TAU in The Netherlands in the treatment of BPD at 18-month follow-up. Further research is needed to investigate treatment outcomes in the longer term and the cost-effectiveness of these treatments.

The dopamine transporter gene (DAT1) and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether a DAT1 haplotype affected functional and structural brain alterations in children with ADHD and whether those alterations were associated with visual memory.

We recruited a total of 37 drug-naïve children with ADHD (17 with the DAT1 rs27048 (C)/rs429699 (T) haplotype and 20 without the CT haplotype) and 37 typically developing children (17 with the CT haplotype and 20 without the CT haplotype). Visual memory was assessed by the pattern recognition memory (PRM) and spatial recognition memory (SRM) tasks. We analyzed functional and structural brain architecture with regional homogeneity (ReHo) and gray matter volume (GMV).

The CT haplotype was associated with decreased ReHo in the left superior occipital gyrus, cuneus, and precuneus; and decreased GMV in the left superior occipital gyrus, cuneus, and precuneus, and in the right angular gyrus. Significant interactions of ADHD and the CT haplotype were found in the right postcentral gyrus for ReHo and in the right supplementary motor area for GMV. For the ADHD-CT group, we found negative correlations of total correct responses in PRM and SRM and positive correlations of mean latency of correct responses in PRM with the GMV in the left superior occipital gyrus, cuneus, and precuneus.

Our findings suggest that the DAT1-related GMV alterations in the posterior cortical regions may contribute to visual memory performance in children with ADHD.

Previous work has shown that amygdala responsiveness to fearful expressions is inversely related to level of callous-unemotional (CU) traits (i.e. reduced guilt and empathy) in youth with conduct problems. However, some research has suggested that the relationship between pathophysiology and CU traits may be different in those youth with significant prior trauma exposure.

In experiment 1, 72 youth with varying levels of disruptive behavior and trauma exposure performed a gender discrimination task while viewing morphed fear expressions (0, 50, 100, 150 fear) and Blood Oxygenation Level Dependent responses were recorded. In experiment 2, 66 of these youth performed the Social Goals Task, which measures self-reports of the importance of specific social goals to the participant in provoking social situations.

In experiment 1, a significant CU traits-by-trauma exposure interaction was observed within right amygdala; fear intensity-modulated amygdala responses negatively predicted CU traits for those youth with low levels of trauma but positively predicted CU traits for those with high levels of trauma. In experiment 2, a bootstrapped model revealed that the indirect effect of fear intensity amygdala response on social goal importance through CU traits is moderated by prior trauma exposure.

This study, while exploratory, indicates that the pathophysiology associated with CU traits differs in youth as a function of prior trauma exposure. These data suggest that prior trauma exposure should be considered when evaluating potential interventions for youth with high CU traits.

Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.

A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.

At baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).

Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.

Although childhood adversity is a potent determinant of psychopathology, relatively little is known about how the characteristics of adversity exposure, including its developmental timing or duration, influence subsequent mental health outcomes. This study compared three models from life course theory (recency, accumulation, sensitive period) to determine which one(s) best explained this relationship.

Prospective data came from the Avon Longitudinal Study of Parents and Children (n = 7476). Four adversities commonly linked to psychopathology (caregiver physical/emotional abuse; sexual/physical abuse; financial stress; parent legal problems) were measured repeatedly from birth to age 8. Using a statistical modeling approach grounded in least angle regression, we determined the theoretical model(s) explaining the most variability (r2) in psychopathology symptoms measured at age 8 using the Strengths and Difficulties Questionnaire and evaluated the magnitude of each association.

Recency was the best fitting theoretical model for the effect of physical/sexual abuse (girls r2 = 2.35%; boys r2 = 1.68%). Both recency (girls r2 = 1.55%) and accumulation (boys r2 = 1.71%) were the best fitting models for caregiver physical/emotional abuse. Sensitive period models were chosen alone (parent legal problems in boys r2 = 0.29%) and with accumulation (financial stress in girls r2 = 3.08%) more rarely. Substantial effect sizes were observed (standardized mean differences = 0.22–1.18).

Child psychopathology symptoms are primarily explained by recency and accumulation models. Evidence for sensitive periods did not emerge strongly in these data. These findings underscore the need to measure the characteristics of adversity, which can aid in understanding disease mechanisms and determining how best to reduce the consequences of exposure to adversity.

Despite increasing evidence for the benefits of psychological treatments (PTs) in low- and middle-income countries, few national health systems have adopted PTs as standard care. We aimed to evaluate the effectiveness of a group interpersonal psychotherapy (IPT-G) intervention, when delivered by lay community health workers (LCHWs) in a low-resource government health system in Uganda. The intended outcome was reduction of depression among caregivers of children with nodding syndrome, a neuropsychiatric condition with high morbidity, mortality and social stigma.

A non-randomized trial design was used. Caregivers in six villages (n = 69) received treatment as usual (TAU), according to government guidelines. Caregivers in seven villages (n = 73) received TAU as well as 12 sessions of IPT-G delivered by LCHWs. Primary outcomes were caregiver and child depression assessed at 1 and 6 months post-intervention.

Caregivers who received IPT-G had a significantly greater reduction in the risk of depression from baseline to 1 month [risk ratio (RR) 0.25, 95% confidence interval (CI) 0.10–0.62] and 6 months (RR 0.33, 95% CI 0.11–0.95) post-intervention compared with caregivers who received TAU. Children of caregivers who received IPT-G had significantly greater reduction in depression scores than children of TAU caregivers at 1 month (Cohen's d = 0.57, p = 0.01) and 6 months (Cohen's d = 0.54, p = 0.03). Significant effects were also observed for psychological distress, stigma and social support among caregivers.

IPT-G delivered within a low-resource health system is an effective PT for common mental health problems in caregivers of children with a severe neuropsychiatric condition and has psychological benefits for the children as well. This supports national health policy initiatives to integrate PTs into primary health care services in Uganda.

Habits are behavioral routines that are automatic and frequent, relatively independent of any desired outcome, and have potent antecedent cues. Among individuals with anorexia nervosa (AN), behaviors that promote the starved state appear habitual, and this is the foundation of a recent neurobiological model of AN. In this proof-of-concept study, we tested the habit model of AN by examining the impact of an intervention focused on antecedent cues for eating disorder routines.

The primary intervention target was habit strength; we also measured clinical impact via eating disorder psychopathology and actual eating. Twenty-two hospitalized patients with AN were randomly assigned to 12 sessions of either Supportive Psychotherapy or a behavioral intervention aimed at cues for maladaptive behavioral routines, Regulating Emotions and Changing Habits (REaCH).

Covarying for baseline, REaCH was associated with a significantly lower Self-Report Habit Index (SRHI) score and significantly lower Eating Disorder Examination-Questionnaire (EDE-Q) global score at the end-of-treatment. The end-of-treatment effect size for SRHI was d = 1.28, for EDE-Q was d = 0.81, and for caloric intake was d = 1.16.

REaCH changed habit strength of maladaptive routines more than an active control therapy, and targeting habit strength yielded improvement in clinically meaningful measures. These findings support a habit-based model of AN, and suggest habit strength as a mechanism-based target for intervention.

Substance use disorder is highly prevalent in people with psychiatric disorders, and known to impede the psychiatric treatment. Some studies show increased rates of service use, while others show a decrease. These conflicting results are further hampered by a lack of large-scale studies. The aim of this study was to investigate the association between substance use disorder and psychiatric service use in psychiatric patients.

The study was a prospective registry-based cohort study including patients with severe mental illness. The primary outcome was the number of hospitalisations, bed days and the number of psychiatric emergency department contacts. The association was calculated with incidence rate ratio with 95% confidence intervals.

The study included all psychiatric patients born since 1955. In total, 21 558 patients with schizophrenia (47.54% with substance use disorder), 80 778 patients with depression (28.78% with substance use disorder), 10 560 patients with bipolar affective disorder (40.08% with substance use disorder) and 69 252 patients with a personality disorder (39.18% with substance use disorder) were included. Patients with comorbid substance use disorder had significantly increased rates of hospitalisations, bed days and psychiatric emergency department contacts (p < 0.001) for the majority of the included substances, compared with patients without such disorders.

Substance use disorder was associated with an increased number of hospitalisations, bed days and increased number of psychiatric emergency department contacts for the majority of the included substances.

Anabolic-androgenic steroid (AAS) use is known to be associated with other psychiatric disorders, such as body image disorders, conduct disorder/sociopathy, and other substance use disorders (SUD) – but the causal pathways among these conditions remain poorly delineated.

We created a directed acyclic graph to diagram hypothesized relationships among AAS use and dependence, body image disorder (BID), conduct disorder/sociopathy, and other SUD. Using proportional hazards models, we then assessed potentially causal relationships among these variables, using a dataset of 233 male weightlifters, of whom 102 had used AAS.

BID and conduct disorder/sociopathy both strongly contributed to the development of AAS use, but did not appear to contribute further to the progression from AAS use to AAS dependence. Other SUD beginning prior to first AAS use – whether broadly defined or restricted only to opioids – failed to show an effect on AAS use or progression to AAS dependence. Conversely, AAS use contributed significantly to the subsequent first-time development of opioid use disorders but did not significantly increase the risk for first-time development of non-opioid SUD, taken as a whole.

Our analysis suggests that AAS use and other SUD are mutually attributable to underlying conduct disorder/sociopathy. SUD do not appear to represent a ‘gateway’ to subsequent AAS use. AAS use may represent a gateway to subsequent opioid use disorder, but probably not to other SUD.

Psychoses, especially schizophrenia, are often preceded by cognitive deficits and psychosis risk states. Altered metabolic profiles have been found in schizophrenia. However, the associations between metabolic profiles and poorer cognitive performance and psychosis risk in the population remain to be determined.

Detailed molecular profiles were measured for up to 8976 individuals from two general population-based prospective birth cohorts: the Northern Finland Birth Cohort 1986 (NFBC 1986) and the Avon Longitudinal Study of Parents and Children (ALSPAC). A high-throughput nuclear magnetic resonance spectroscopy platform was used to quantify 70 metabolic measures at age 15–16 years in the NFBC 1986 and at ages 15 and 17 years in ALSPAC. Psychosis risk was assessed using the PROD-screen questionnaire at age 15–16 years in the NFBC 1986 or the psychotic-like symptoms assessment at age 17 years in ALSPAC. Cognitive measures included academic performance at age 16 years in both cohorts and general intelligence and executive function in ALSPAC. Logistic regression measured cross-sectional and longitudinal associations between metabolic measures and psychosis risk and cognitive performance, controlling for important covariates.

Seven metabolic measures, primarily fatty acid (FA) measures, showed cross-sectional associations with general cognitive performance, four across both cohorts (low density lipoprotein diameter, monounsaturated FA ratio, omega-3 ratio and docosahexaenoic acid ratio), even after controlling for important mental and physical health covariates. Psychosis risk showed minimal metabolic associations.

FA ratios may be important in marking risk for cognitive deficits in adolescence. Further research is needed to clarify whether these biomarkers could be causal and thereby possible targets for intervention.

Impulsivity and compulsivity are central to understanding a range of psychiatric disorders but also to understanding the spectrum of normative human behavior. It was recently shown that separable latent phenotypes of impulsivity and compulsivity could be fractionated. The possible genetic contributions to these latent phenotypes have yet to be elicited. The catechol-o-methyl transferase (COMT) Val158Met polymorphism (rs4680) regulates cortical dopamine degradation and is a key area of interest in this context.

COMT Val158Met polymorphism status was obtained from a random subset (n = 258) of young adults from an established cohort, for whom latent phenotype scores were previously reported. Differences in latent phenotype scores were explored between COMT groups using analysis of variance (ANOVA) and post-hoc t tests.

The Val-Val subgroup exhibited significantly elevated compulsivity scores compared to both other groups. Impulsivity scores did not differ significantly as a function of COMT Val158Met polymorphism status.

These results suggest that the COMT polymorphism, and by implication cortical dopamine degradation, influences the expression of a trans-diagnostic compulsivity phenotype, even accounting for possible confounding effects of impulsivity.