Stigmatization in society carries a high risk for development of psychopathology. Transgender persons are at particularly high risk for such stigmatization and social rejection by others. However, the neural correlates of ostracism in this group have not been captured.

Twenty transgender men (TM, female-to-male) and 19 transgender women (TW, male-to-female) already living in their gender identity and 20 cisgender men (CM) and 20 cisgender women (CW) completed a cyberball task assessing both exclusion and re-inclusion during functional magnetic resonance imaging (fMRI).

During psychosocial stress between-group differences were found in the dorsal and ventral anterior cingulate cortex (ACC) and the inferior frontal gyrus (IFG). Patterns were consistent with sex assigned at birth, i.e. CW showed greater activation in dorsal ACC and IFG relative to CM and TW. During re-inclusion, transgender persons showed greater ventral ACC activity relative to CW, possibly indicating persistent feelings of exclusion. Functional connectivity analyses supported these findings but showed a particularly altered functional connectivity between ACC and lateral prefrontal cortex in TM, which may suggest reduced emotional regulation to the ostracism experience in this group. Depressive symptoms or hormonal levels were not associated with these findings.

The results bear implications for the role of social exclusion in development of mental health problems in socially marginalized groups.

One of the most consistently reported brain abnormalities in schizophrenia (SCZ) is decreased volume and shape deformation of the hippocampus. However, the potential contribution of chronic antipsychotic medication exposure to these phenomena remains unclear.

We examined the effect of chronic exposure (8 weeks) to clinically relevant doses of either haloperidol (HAL) or olanzapine (OLZ) on adult rat hippocampal volume and shape using ex vivo structural MRI with the brain retained inside the cranium to prevent distortions due to dissection, followed by tensor-based morphometry (TBM) and elastic surface-based shape deformation analysis. The volume of the hippocampus was also measured post-mortem from brain tissue sections in each group.

Chronic exposure to either HAL or OLZ had no effect on the volume of the hippocampus, even at exploratory thresholds, which was confirmed post-mortem. In contrast, shape deformation analysis revealed that chronic HAL and OLZ exposure lead to both common and divergent shape deformations (q = 0.05, FDR-corrected) in the rat hippocampus. In particular, in the dorsal hippocampus, HAL exposure led to inward shape deformation, whereas OLZ exposure led to outward shape deformation. Interestingly, outward shape deformations that were common to both drugs occurred in the ventral hippocampus. These effects remained significant after controlling for hippocampal volume suggesting true shape changes.

Chronic exposure to either HAL or OLZ leads to both common and divergent effects on rat hippocampal shape in the absence of volume change. The implications of these findings for the clinic are discussed.

Alcohol use disorder (AUD) is a classic multifactorial syndrome and it is critical to understand the diversity of the relevant risk factors and how they inter-relate over development.

We examined 21 risk factors for AUD in four developmental tiers reflecting (i) birth, (ii) childhood and early adolescence, (iii) late adolescence, and (iv) early adulthood in 47 414 Swedish men of whom 3907 (8.2%) were registered for AUD at or after age 25 with a mean length of follow-up of 33.9 (6.6) years. Structural equational model fitting was performed using Mplus.

The best-fitting model provided a good fit to the data and explained 23.4% of the variance in AUD. The five strongest predictors were: externalizing behaviors, criminal behavior, father's alcohol consumption, genetic risk, and low educational attainment. Two developmentally early familial/genetic risk factors had substantial direct paths to AUD: father's alcohol consumption and genetic liability. Other broad developmental pathways to risk for AUD were evident: externalizing, psychosocial and internalizing. Overall, the externalizing pathway to AUD was the strongest. However, these pathways were substantially interwoven over time such that risk factors from one domain were commonly predicted by and/or predicted risk factors from the other broad domains of risk.

AUD in men is an etiologically complex syndrome influenced by familial-genetic, psychosocial, internalizing, and especially externalizing risk factors that act and interact over development and have complicated mediational pathways.

The Community Assessment of Psychic Experiences (CAPE) is a 42-item self-report questionnaire that has been developed and validated to measure the dimensions of psychosis in the general population. The CAPE has a three-factor structure with dimensions of positive, negative and depression. Assessing the cross-national equivalence of a questionnaire is an essential prerequisite before pooling data from different countries. In this study, our aim was to investigate the measurement invariance of the CAPE across different countries.

Data were drawn from the European Union Gene-Environment Interaction (EU-GEI) study. Participants (incident cases of psychotic disorder, controls and siblings of cases) were recruited in Brazil, France, Italy, the Netherlands, Spain and UK. To analyse the measurement invariance across these samples, we tested configural invariance (i.e. identical structures of the factors), metric invariance (i.e. equivalence of the factor loadings) and scalar invariance (i.e. equivalence of the thresholds) of the three CAPE dimensions using multigroup categorical confirmatory factor analysis methods.

The configural invariance model fits well, providing evidence for identical factorial structure across countries. In comparison with the configural model invariance, the fit indices were very similar in the metric and scalar invariance models, indicating that factor loadings and thresholds did not differ across the six countries.

We found that, across six countries, the CAPE showed equivalent factorial structure, factor loadings and thresholds. Thus, differences observed in scores between individuals from different countries should be considered as reflecting different levels of psychosis.

Depression is one of the most common and debilitating non-motor symptoms of Parkinson's disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal.

We investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging in 22 non-depressed PD patients and 19 PD patients with past or present depression.

PD patients with a depression (history) exhibited impaired reward v. punishment reversal learning as well as reduced reward v. punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed.

The present findings demonstrate that impairments in reversal learning from reward v. punishment and associated striatal signalling depend on the presence of (a history of) depression in PD.

The outbreak and rapid spread of coronavirus disease 2019 (COVID-19) not only caused an adverse impact on physical health, but also brought about mental health problems among the public.

To assess the causal impact of COVID-19 on psychological changes in China, we constructed a city-level panel data set based on the expressed sentiment in the contents of 13 million geotagged tweets on Sina Weibo, the Chinese largest microblog platform.

Applying a difference-in-differences approach, we found a significant deterioration in mental health status after the occurrence of COVID-19. We also observed that this psychological effect faded out over time during our study period and was more pronounced among women, teenagers and older adults. The mental health impact was more likely to be observed in cities with low levels of initial mental health status, economic development, medical resources and social security.

Our findings may assist in the understanding of mental health impact of COVID-19 and yield useful insights into how to make effective psychological interventions in this kind of sudden public health event.

Smoking tobacco is regarded as an epiphenomenon in patients with schizophrenia when it may be causal. We aimed to examine whether smoking status is related to the onset of schizophrenia or the broader diagnosis of non-affective psychosis, including schizophrenia.

We used data from The Health Improvement Network primary care database to identify people aged 15–24 between 1 January 2004 and 31 December 2009. We followed them until the earliest of: first diagnosis of schizophrenia (or psychosis), patient left the practice, practice left THIN, patient died or 31 December 2014.

In men, incidence rates for schizophrenia per 100 000 person years at risk were higher in smoking initiators (non-smoker who became a smoker during the study) than in non-smokers (adjusted IRR 1.94; 95% CI 1.29–2.91) and higher still in smokers (adjusted IRR 3.32; 95% CI 2.67–4.14). Among women, the incidence rate of schizophrenia was higher in smokers than in non-smokers (adjusted IRR 1.50; 95% CI 1.06–2.12), but no higher in smoking initiators than non-smokers. For non-affective psychosis, the pattern was similar for men but more evident in women where psychosis incidence rates were higher in smoking initiators (adjusted IRR 1.90; 95% CI 1.40–2.56) and in smokers (adjusted IRR 2.13; 95% CI 1.76–2.57) than in non-smokers.

We found an important and strong association between smoking and incidence of schizophrenia. Smoking may increase risk through as yet unknown pathways or smoking may share genetic risk with schizophrenia and non-affective psychoses.

Two prominent risk factors for major depressive disorder (MDD) are childhood maltreatment (CM) and familial risk for MDD. Despite having these risk factors, there are individuals who maintain mental health, i.e. are resilient, whereas others develop MDD. It is unclear which brain morphological alterations are associated with this kind of resilience. Interaction analyses of risk and diagnosis status are needed that can account for complex adaptation processes, to identify neural correlates of resilience.

We analyzed brain structural data (3T magnetic resonance imaging) by means of voxel-based morphometry (CAT12 toolbox), using a 2 × 2 design, comparing four groups (N = 804) that differed in diagnosis (healthy v. MDD) and risk profiles (low-risk, i.e. absence of CM and familial risk v. high-risk, i.e. presence of both CM and familial risk). Using regions of interest (ROIs) from the literature, we conducted an interaction analysis of risk and diagnosis status.

Volume in the left middle frontal gyrus (MFG), part of the dorsolateral prefrontal cortex (DLPFC), was significantly higher in healthy high-risk individuals. There were no significant results for the bilateral superior frontal gyri, frontal poles, pars orbitalis of the inferior frontal gyri, and the right MFG.

The healthy high-risk group had significantly higher volumes in the left DLPFC compared to all other groups. The DLPFC is implicated in cognitive and emotional processes, and higher volume in this area might aid high-risk individuals in adaptive coping in order to maintain mental health. This increased volume might therefore constitute a neural correlate of resilience to MDD in high risk.

Individual with internet gaming disorder (IGD) often experience a high level of loneliness, and neuroimaging studies have demonstrated that amygdala function is associated with both IGD and loneliness. However, the neurobiological basis underlying these relationships remains unclear.

In the current study, Granger causal analysis was performed to investigate amygdalar subdivision-based resting-state effective connectivity differences between 111 IGD subjects and 120 matched participants with recreational game use (RGUs). We further correlated neuroimaging findings with clinical measures. Mediation analysis was conducted to explore whether amygdalar subdivision-based effective connectivity mediated the relationship between IGD severity and loneliness.

Compared with RGUs, IGD subjects showed inhibitory effective connections from the left pregenual anterior cingulate cortex (pACC) to the left laterobasal amygdala (LBA) and from the right medial prefrontal cortex (mPFC) to the left LBA, as well as an excitatory effective connection from the left middle prefrontal gyrus (MFG) to the right superficial amygdala. Further analyses demonstrated that the left pACC-left LBA effective connection was negatively correlated with both Internet Addiction Test and UCLA Loneliness scores, and it mediated the relationship between the two.

IGD subjects and RGUs showed different connectivity patterns involving amygdalar subdivisions. These findings support a neurobiological mechanism for the relationship between IGD and loneliness, and suggest targets for therapeutic approaches that could be used to treat IGD.

Although many studies have addressed the topic of stability versus change in depressive symptoms, few have further decomposed the change to continuous accumulation versus non-systematic state fluctuations or measurement errors. This further step requires a longitudinal follow-up and an appropriate stochastic model; it would, for example, evaluate the hypothesis that women accumulate more susceptibility events than men.

A linear stochastic differential equation model was estimated for a 16-year longitudinal course of depressive symptoms in the Young Finns community sample of 3596 participants (1832 women, 1764 men). This model enabled us to decompose the variance in depression symptoms into a stable trait, cumulative effects and state/error fluctuations.

Women showed higher mean levels and higher variance of depressive symptoms than men. In men, the stable trait accounted for the majority [61%, 90% confidence interval (CI) 48.9–69.2] of the total variance, followed by cumulative effects (23%, 90% CI 9.9–41.7) and state/error fluctuations (16%, 90% CI 5.6–23.2). In women, the cumulative sources were more important than among men and accounted for 44% (90% CI 23.6–58.9) of the variance, followed by stable individual differences (32%, 90% CI 18.5–54.2) and state fluctuations (24%, 90% CI 19.1–27.3).

The results are consistent with previous observations that women suffer more depression than men, and have more variance in depressive symptoms. We also found that continuously accumulating effects are a significant contributor to between-individual differences in depression, especially for women. Although the accumulating effects are often confounded with non-systematic state fluctuations, the latter are unlikely to exceed 27% of the total variance of depressive symptoms.

As children with attention-deficit/hyperactivity disorder (ADHD) usually show psychopathological signs beyond their core symptoms (e.g. elevated scores of the dysregulation profile (DP) in 30–40%), treatments with a broader approach to self-regulation skills may be supportive. Neurofeedback (NF) may reflect such an option. Aim of the present analysis was to compare the effects of slow cortical potential (SCP) NF and θ/β NF on the DP using data from a previous trial.

Thirty children with ADHD (aged 8–12 years) and a DP score in the Strengths and Difficulties Questionnaire (SDQ-DP) ⩾ 3 were included. NF treatment consisted of one block of SCP NF and one block of θ/β NF (18 units per block) allowing an intraindividual comparison. Effects of the NF protocols were also contrasted to a control group (n = 18) that completed an attention skills training (between-group analysis).

Regarding the SDQ-DP, SCP NF was superior to θ/β NF and the control condition. Effects of SCP NF and θ/β NF on ADHD symptom severity were not significantly different. The SDQ-DP score did not correlate with EEG-related measures previously found to be predictors for SCP NF on ADHD symptoms.

SCP NF may reflect a more general approach to improve cognitive, emotional and behavioral self-regulation skills. If confirmed in a larger sample, the SDQ-DP score could be used as an indication criterion and contribute to the individualization of NF in ADHD. Overall, the differential effect provides further evidence for the specificity of NF effects.

Ethnic minority individuals have an increased risk of developing a psychotic disorder, particularly if they live in areas of ethnic segregation, or low own group ethnic density. The neurobiological mechanisms underlying this ethnic minority associated risk are unknown. We used functional MRI to investigate neural responses to faces of different ethnicity, in individuals of black ethnicity, and a control group of white British ethnicity individuals.

In total 20 individuals of black ethnicity, and 22 individuals of white British ethnicity underwent a 3T MRI scan while viewing faces of black and white ethnicity. Own group ethnic density was calculated from the 2011 census. Neighbourhood segregation was quantified using the Index of Dissimilarity method.

At the within-group level, both groups showed greater right amygdala activation to outgroup faces. Between groups, the black ethnicity group showed greater right amygdala activation to white faces, compared to the white ethnicity group. Within the black ethnicity group, individuals living in areas of lower own group ethnic density showed greater right amygdala reactivity to white faces (r = −0.61, p = 0.01).

This is the first time an increased amygdala response to white faces has been demonstrated in individuals of black ethnicity. In the black ethnicity group, correlations were observed between amygdala response and neighbourhood variables associated with increased psychosis risk. These results may have relevance for our understanding of the increased rates of paranoia and psychotic disorders in ethnic minority individuals.

Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner.

Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N = 3212–5369 per phenotype).

The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints [β = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; β = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls.

Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific.

Impulsivity may be a process underlying binge-eating disorder (BED) psychopathology and its treatment. This study examined change in impulsivity during cognitive-behavioral therapy (CBT) and/or pharmacological treatment for BED and associations with treatment outcomes.

In total, 108 patients with BED (NFEMALE = 84) in a randomized placebo-controlled clinical trial evaluating the efficacy of CBT and/or fluoxetine were assessed before treatment, monthly throughout treatment, at post-treatment (16 weeks), and at 12-month follow-up after completing treatment. Patients completed established measures of impulsivity, eating-disorder psychopathology, and depression, and were measured for height and weight [to calculate body mass index (BMI)] during repeated assessments by trained/monitored doctoral research-clinicians. Mixed-effects models using all available data examined changes in impulsivity and the association of rapid and overall changes in impulsivity on treatment outcomes. Exploratory analyses examined whether baseline impulsivity predicted/moderated outcomes.

Impulsivity declined significantly throughout treatment and follow-up across treatment groups. Rapid change in impulsivity and overall change in impulsivity during treatment were significantly associated with reductions in eating-disorder psychopathology, depression scores, and BMI during treatment and at post-treatment. Overall change in impulsivity during treatment was associated with subsequent reductions in depression scores at 12-month follow-up. Baseline impulsivity did not moderate/predict eating-disorder outcomes or BMI but did predict change in depression scores.

Rapid and overall reductions in impulsivity during treatment were associated with improvements in specific eating-disorder psychopathology and associated general outcomes. These effects were found for both CBT and pharmacological treatment for BED. Change in impulsivity may be an important process prospectively related to treatment outcome.

Expressive writing about a traumatic event is promising in treating posttraumatic stress disorder (PTSD) symptoms in adult trauma survivors. To date, the comparative efficacy and acceptability of this approach is uncertain. Therefore, we aimed to examine the comparative efficacy and acceptability of expressive writing treatments.

We included 44 RCTs with 7724 participants contributing 54 direct comparisons between expressive writing (EW), enhanced writing (i.e. including additional therapist contact or individualized writing assignments; EW+), PTSD psychotherapies (PT), neutral writing (NW), and waiting-list control (WL).

EW, EW+, PT, and NW were statistically significantly more efficacious than WL at the longest available follow-up, with SMDs (95% CI) of −0.78 (−1.10 to −0.46) for PT, −0.81 (−1.02 to −0.61) for EW+ , −0.43 (−0.65 to −0.21) for EW, and −0.37 (−0.61 to −0.14) for NW. We found small to moderate differences between the active treatments. At baseline mean PTSD severity was significantly lower in EW+ compared with WL. We found considerable heterogeneity and inconsistency and we found elevated risk of bias in at least one of the bias dimensions in all studies. When EW+-WL comparisons were excluded from the analyses EW+ was no longer superior compared with EW.

The summarized evidence confirms that writing treatments may contribute to improving PTSD symptoms in medium to long-term. Methodological issues in the available evidence hamper definite conclusions regarding the comparative efficacy and acceptability of writing treatments. Adequately sized comparative randomized controlled trials preferably including all four active treatment approaches, reporting long-term data, and including researchers with balanced preferences are needed.