Exercise improves stress perception and sleep quality and reduces repetitive negative thinking in patients with various mental disorders. However, it is unclear whether changes in these processes mediate treatment effects on psychopathology in a transdiagnostic sample.

Physically inactive adult outpatients with depressive disorders, agoraphobia, panic disorder, post-traumatic stress disorder, and/or nonorganic primary insomnia were randomly allocated to ImPuls – a 6-month transdiagnostic group exercise intervention – plus treatment-as-usual (n = 198), or to a treatment-as-usual alone control group (n = 201) at 10 study sites between March 2021 and May 2022. The primary outcome was global symptom severity; perceived stress, repetitive negative thinking, and sleep quality were included as mediators. All variables were assessed at baseline, 6 months, and 12 months using validated rating scales. As a secondary analysis of an RCT, intention-to-treat analyses were performed using structural equation modeling to test whether changes in stress perception, repetitive negative thinking, and sleep quality mediate treatment effects on changes in global symptom severity in two path models (from baseline to 6 and 12 months, respectively).

Treatment effects on global symptom severity were fully mediated by changes in perceived stress (6 months: β = −0.99, p = .024; 12 months: β = −1.28, p = .014) and repetitive negative thinking (6 months: β = −1.34, p = .004; 12 months: β = −0.94, p = .024).

Our results suggest that changes in perceived stress and repetitive negative thinking may be key transdiagnostic mechanisms underlying the treatment effect of exercise on global symptom severity.

The results of a previous randomized trial showed that mentalization-based treatment for psychotic disorder (MBTp) was associated with greater improvement than treatment as usual (TAU) in social functioning up to 6 months after treatment. The purpose of the present study is to examine the effect after 5 years.

The researchers tried to find all patients who had participated in the trial (n = 84) and to assess, blind to previous treatment status, their social functioning and mentalizing capacity. Social functioning was measured using the Social Functioning Scale, mentalizing using the Social Cognition and Object Relations Scale and the Hinting Task.

Twenty-three MBTp patients and 23 TAU patients collaborated. There was no evidence of selective drop-out. A complete case, repeated measure analysis of variance on the basis of intention-to-treat showed that, 5 years post-treatment, MBTp patients still scored better on social functioning compared to baseline [ηp2 = .25, p = .01], whereas TAU patients did not [ηp2 = .01, p = .67], with a significant difference between the conditions [ηp2 = .10, p = .03]. A sensitivity analysis with linear mixed models, however, showed weaker evidence for an additive effect of MBTp over TAU on social functioning 5 years post-treatment, F = 3.731, p = .06. MBT patients also showed a greater improvement in one aspect of mentalizing, understanding of social causality [ηp2 = 0.17, p = .04], but not other aspects of mentalizing.

The results suggest a durable effect of MBTp.

Growing studies have reported an elevated risk of violence in patients with depression, yet the neurobiological underpinnings remain poorly understood. The present study explored the resting-state electroencephalogram (EEG) features in major depressive disorder (MDD) patients with violent offenses to identify potential neurological markers for violence prediction and intervention.

Twenty-nine MDD patients who committed violent offenses (violent depression [VD] group), 27 MDD patients without violent behaviors (nonviolent depression [NVD] group), and 25 healthy controls (HCs) were included. Resting-state EEGs were recorded for at least 5 min. EEG microstates, functional connectivity (FC), and graph theory metrics were analyzed and compared between groups.

First, the VD group had increased microstate A, more microstates A-B transition, but lower microstates B-D and C-D transition. Second, the VD group exhibited two enhanced functional brain networks compared to NVD and HCs, and three weakened functional brain networks compared to HCs, which were primarily distributed in the frontal and frontoparietal networks. Third, the VD group specifically exhibited reduced nodal efficiency (aNe) in the superior parietal lobe and increased aNe in the middle occipital gyrus.

MDD patients with violent offenses exhibited alterations in EEG microstates, FCs in the frontal lobe and frontoparietal network, and disrupted aNe in specific parietal and occipital lobes. These alternations are closely associated with deficits in emotional regulation, executive function, and inhibitory control, which may subserve as potential neurobiomarkers for violence risk assessment in patients with depression.

Cumulative stress exposure is extensively involved in carcinogenesis. However, cancer risk associated with allostatic load (AL), a valid measure of chronic stress, has not been comprehensively evaluated in large cohorts, and the combined effect of AL and personality trait on cancer risk remains unknown.

This prospective cohort study was conducted based on 245,683 participants from the UK Biobank, with a median follow-up of 13.5 years. The AL score was calculated based on 11 biomarkers. Personality traits were constructed and categorized into two clusters. Multivariable Cox regression model was used to assess the risk of incident cancer according to AL and personality clusters, and multiplicative and additive interactions were evaluated.

High AL was associated with an increased cancer risk compared to low AL (hazard ratio [HR] = 1.06, 95% confidence interval [CI]: 1.04–1.09), particularly for cancers of stomach, liver, kidney, esophageal, lung, colorectal, breast, and leukemia (HR ranged from 1.08 to 1.43). Personality clusters was associated with risk of lung cancer (HR = 1.14, 95% CI: 1.05–1.23), but not overall cancer. Significant synergistic interaction was observed between high AL and ‘nervous-dominant’ personality for overall cancer risk, with the strongest association observed for liver cancer (HR = 1.58, 95% CI: 1.24–2.02).

High AL was related to higher risks of overall cancer and site-specific cancers, particularly when combined with nervous-dominant personality, highlighting the interplay between chronic physiological stress and psychological factors in cancer development.

Evidence regarding the effects of antipsychotic medication on cognitive functioning after a first-episode psychosis (FEP) remains inconclusive. This study examined whether dopamine D2 receptor occupancy, affinity, and antipsychotic dose are related to cognitive functioning in people in remission from FEP.

278 remitted FEP participants from the HAMLETT-trial were included. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia, 3–6 months after remission. D2 receptor occupancy was estimated based on antipsychotic type and dose. Antipsychotics were categorized into partial agonists, or antagonists with high or low D2 receptor affinity. Linear regression analyses were performed with inverse probability of treatment weighting to control for differences in characteristics between groups.

D2 receptor occupancy was negatively related to global cognition (β = −0.18), verbal fluency (β = −0.22), and attention and processing speed (β = −0.17, all p < 0.003). The interaction between daily dose and D2 receptor affinity category was significant for global cognition (p = 0.0046) and working memory (p = 0.0019), but not for verbal fluency after correction for multiple testing (p = 0.029). Interactions showed that higher daily dose was related to lower cognitive functioning, with significantly stronger negative effects in high-affinity antagonists compared to other antipsychotics.

The current findings underscore the importance of antipsychotic D2 receptor occupancy and affinity for cognitive functioning and suggest better cognitive functioning in users of partial agonists and low D2 receptor affinity antipsychotics. This can be important when selecting antipsychotics for individuals with FEP.

While prenatal exposure to tobacco has been associated with adolescent suicide attempt, little is known about the mechanisms explaining this association. This study aims to explore the mediating roles of internalizing symptoms, externalizing behaviors, and peer problems across childhood in the association between prenatal exposure to tobacco and adolescent suicide attempt.

We analyzed data from N = 8,861 participants from the Millennium Cohort Study followed from ages 9 months to 17 years. Binary logistic regression models were used to investigate the total association between exposure to tobacco in pregnancy and suicide attempt, and mediation analyses were conducted using structural equation models to investigate the direct and indirect associations.

In models adjusted for key covariates, we found a significant association between prenatal tobacco exposure and increased risk of adolescent suicide attempts (odds ratio = 2.08, 95% confidence interval = [1.68, 2.56]), partly mediated through internalizing problems, externalizing behaviors, and peer problems from ages 3 to 14 years (accounting for 37% of the total association, that is, 16%, 12%, and 9%, respectively).

These findings suggest that interventions targeting mental health symptoms and peer problems may maximize suicide prevention efforts among children who were prenatally exposed to tobacco, thus potentially reducing the long-term risk of suicide attempt.

Adults with intellectual disability (ID) experience marked mental health inequities, yet population-wide estimates that capture both primary- and specialist-care diagnoses remain scarce.

Using nationwide Swedish registries, including primary care, specialist, inpatient, prescription drug, criminal, and suspicion registers, we included all individuals born in Sweden between 1958 and 1997 (N = 3,970,600), including 38,818 individuals with ID diagnoses (0.98%; 49.1% mild, 13.3% moderate, and 9.6% severe/profound). Hazard ratios (HR) were calculated using Cox proportional hazards regression to estimate the relative risk of lifetime diagnoses of major depression, anxiety disorders (ANX), obsessive-compulsive disorder (OCD), bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), drug use disorder, alcohol use disorder, schizophrenia, and other nonaffective psychosis. Additionally, cohort effects on psychiatric diagnosis risks in adults with intellectual disabilities versus the general population were evaluated.

People with ID were at higher risk for all psychiatric and substance use disorders, with HRs ranging from 1.7–2.0 for major depression and anxiety, drug and alcohol use disorders, 3.5–5.8 for BD, OCD and ADHD, and 10.9–12.7 for schizophrenia and other nonaffective psychosis. Higher prevalence was consistently seen among those with mild versus moderate or severe/profound intellectual disability. Relative risks narrowed modestly in successive birth cohorts, although absolute differences remained substantial.

Across six decades of follow-up, adults with ID faced markedly higher psychiatric and substance-use morbidity – most pronounced for psychotic disorders – than the general population. Whole-system mental-health screening and tailored interventions are required to address this persistent disparity.

While mobile gaming addiction (MGA) behavior is increasingly prevalent among children and adolescents, the role of specific emotional-behavioral profiles – particularly their latent patterns – in associating with MGA behavior remains poorly understood. This study aimed to examine these associations and age-related variations.

Data were analyzed from 507,188 participants aged 6–18 years in the Children’s Growth Environment, Lifestyle, and Physical and Mental Health Development Project, conducted in Guangzhou, China, in 2020. Latent class analysis was performed on parent-reported Strengths and Difficulties Questionnaire (SDQ) data to identify subgroups with distinct emotional and behavioral problems. Associations between SDQ dimensions, latent classes, and MGA behavior were examined using logistic regression analysis.

Five latent classes were identified: ‘Low symptom’ (82.2%), ‘Internalizing’ (0.8%), ‘Peer and prosocial issues’ (4.3%), ‘High difficulties’ (5.0%), and ‘Hyperactive’ (7.6%). Compared to the ‘Low symptom’ class, all other latent classes showed significantly higher risks for MGA, with the strongest association observed in the ‘Internalizing’ class (adjusted odds ratio [AOR]: 2.84; 95% confidence interval [95% CI]: 2.67–3.02). Among SDQ subscales, conduct problems presented the highest association (AOR: 2.08; 95% CI: 2.04–2.12), though all SDQ subdimensions were significantly positively correlated with MGA behavior (all p < 0.05). Notably, these associations were consistently stronger in adolescents (aged 13–18 years) than in children (aged 6–12 years).

This study identifies specific SDQ-based risk characteristics for MGA behavior, with adolescents (aged 13–18 years) being the most vulnerable. Future longitudinal studies should verify these associations, and clinicians may prioritize early screening for internalizing and conduct-related difficulties.

Impaired social functioning is commonly observed in youth at clinical high risk (CHR) for psychosis. Interpersonal synchrony, defined as the temporal alignment of movement between interacting partners, is a key component of successful social interactions. This study aimed to investigate interpersonal head synchrony in naturalistic virtual settings among CHR individuals using automated video analysis tools.

We analyzed short video recordings from virtual clinical interviews involving 116 participants including 50 CHR participants, 36 individuals with sub-threshold positive symptoms (SUB), and 30 healthy controls (HC). Vertical head movement time series were extracted using an open-access video-based head-tracking tool. Interpersonal head synchrony was computed using Windowed Cross-Correlation to assess group differences and associations with clinical symptoms and functioning.

CHR participants showed significantly reduced strength of synchrony compared to HC (β = −0.05, 95% CI [−0.09, −0.02], p = .004), although 14% of variance in strength of synchrony was attributable to assessor identity. No significant group differences were found for delay of synchrony. Within the CHR group, delay of synchrony was positively associated with social anhedonia (r = 0.29). Strength of synchrony correlated with better social (r = 0.33) and role (r = 0.28) functioning.

Our findings suggest that impaired interpersonal head synchrony is already present in the psychosis-risk state and relates to negative symptoms and social and role functioning. These findings support the utility of nonverbal synchrony as a potential biomarker and demonstrate the feasibility of automated tools and virtual assessments to study social processes in at-risk populations.

Anhedonia is a multidimensional concept, and it is not known which aspects of it are linked to the heterogeneity of treatment responses in major depressive disorder (MDD). We examine the role of anhedonia dimensions in predicting response to antidepressant medication and adjunctive pharmacotherapy.

In CAN-BIND-1, 187 adults with MDD completed the Dimensional Anhedonia Rating Scale (DARS) and the Snaith–Hamilton Pleasure Scale (SHAPS) before undergoing 8 weeks of treatment with escitalopram. At week 8, 90 nonresponders received adjunctive treatment with aripiprazole for an additional 8 weeks. Mixed-effects models tested the hobbies, food, social, and sensory subscales and items of DARS and SHAPS as predictors of change in the Montgomery-Åsberg Depression Rating Scale (MADRS).

Of the four DARS subscales, sensory anhedonia predicted a worse treatment outcome with escitalopram (b = 1.14, 95%CI 0.08 to 2.20, p = 0.034) as did a three-item SHAPS sensory anhedonia subscale (b = 1.50, 95%CI 0.43 to 2.57, p = 0.006). A combined DARS–SHAPS sensory anhedonia subscale complemented the previously reported interest–activity symptom dimension to improve treatment outcome prediction. In contrast, food and social anhedonia dimensions predicted worse outcomes with adjunctive aripiprazole (b = 2.52, 95%CI 1.25 to 3.80, p < 0.001; b = 2.56, 95%CI 1.16 to 3.96, p < 0.001). Corresponding SHAPS items showed similar results.

The inability to enjoy sensory experiences and the lack of interest in food and social activities distinctly predict outcomes with serotonergic versus dopaminergic pharmacotherapy. These findings require replication and extension to other treatments.

Rates of loneliness have increased over the past several decades worldwide, particularly among people with serious mental illnesses. A better understanding of the neurocognitive mechanisms underlying loneliness could provide useful information for the efforts to address this public health problem.

To investigate these mechanisms, a functional magnetic resonance imaging (fMRI) study was conducted which accounted for known cognitive biases associated with loneliness. Participants with (n = 40) and without (n = 60) psychotic disorders (PD) viewed images of faces that appeared to approach or withdraw from the participants while fMRI data were collected. Following the scanning, participants rated the trustworthiness of the faces, and these ratings were included as weights in the fMRI analyses. Neural responses to approaching versus withdrawing faces were measured, and whole-brain regression analyses, with loneliness as the regressor, were performed.

In the PD and full samples, a higher level of loneliness was significantly associated with greater responses of the hippocampus and areas of the basal ganglia to withdrawing (versus approaching) face stimuli. Moreover, the effects in the hippocampus, but not the basal ganglia, remained significant after controlling for potential confounds such as social activity levels, depression and social anhedonia. Finally, in a subset of the full sample (n = 66), greater hippocampal responses to withdrawing faces predicted greater loneliness 1 year later.

Heightened responses of the hippocampus to withdrawing faces may represent a candidate neurobiological marker of loneliness that could be modified by interventions targeting loneliness.

Substantial evidence supports the efficacy of cognitive bias modification (CBM) for attention and interpretation. However, CBM targeting memory bias (CBM-M) remains underexplored despite its clinical relevance. This study examines the effectiveness and neurobiological mechanisms of CBM-M.

Fifty-eight individuals with elevated anxious and depressive personality traits (>1 SD) were randomly assigned to either CBM-M or sham training (n = 29 per group) in a parallel, double-blind, randomized controlled trial. The intervention involved eight sessions over 1 month. CBM-M aimed to enhance positive autobiographical memory (AM) recall by focusing on positive and negative words, whereas sham training lacked this enhancement module. Anxiety and depressive traits and symptoms, explicit and implicit memory biases, and AM specificity were assessed. Additionally, intrinsic functional connectivity was measured via functional magnetic resonance imaging, and cortisol levels were assayed via saliva collected at 10 time points across 2 days before and after the intervention.

Both groups showed reduced anxiety and depressive traits from pre- to post-intervention. Compared with sham training, CBM-M specifically reduced stress vulnerability, negative explicit memory bias, and daytime cortisol levels, with a large effect size. Improvement in memory bias correlated with stress vulnerability and cortisol reductions. CBM-M also enhanced amygdala functional connectivity with the anteromedial orbitofrontal cortex in comparison with sham training from pre- to post-intervention.

CBM-M reduced stress vulnerability and elicited neural changes in amygdala–anteromedial orbitofrontal cortex interactions, which were involved in social reward and AM recall. Future research should identify the most responsive populations and elucidate underlying mechanisms.

Low self-esteem is an important and potentially modifiable risk factor for the development and outcome of psychotic disorders. The factors involved in low self-esteem in psychotic disorders are not yet fully understood. The current study aims to investigate the cross-sectional and longitudinal associations between (changes in) self-esteem and severity of psychotic symptoms, internalized stigma, negative reaction to antipsychotics, personal recovery, childhood bullying, childhood trauma, and social support in symptomatically remitted first-episode psychosis (FEP) patients.

Data from the ongoing longitudinal Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study were used. Participants were in symptomatic remission for 3–6 months after the FEP. Cross-sectional associations (N = 299) were investigated through Pearson’s correlations, and longitudinal changes (N = 238) were investigated via linear regressions with inverse probability weighting.

Cross-sectionally, we found that lower self-esteem was related to higher severity of symptoms, higher internalized stigma, higher childhood trauma (specifically emotional neglect), higher childhood bullying, more negative side effects of antipsychotic medication, lower personal recovery, and lower social support. Longitudinally, contrary to our hypothesis, we found that higher baseline internalized stigma, higher childhood trauma (specifically emotional abuse), and a higher baseline negative subjective reaction to antipsychotics predicted an increase in self-esteem after 6 months. Furthermore, a decrease in psychotic symptoms, internalized stigma, and negative subjective reaction to antipsychotics, and an increase in social support predicted an increase in self-esteem.

Early intervention programs for psychotic disorders should target factors related to changes in self-esteem. This might improve self-esteem and thereby promote recovery.

Although the short-term preventive effects of mHealth consultation intervention on postpartum depressive symptoms have been demonstrated, the long-term effects and role of alleviating loneliness on depressive symptoms remain unclear.

This follow-up study extended our previous trial, which ended at three months postpartum, by continuing observation to 12 months. Participants in the original trial were randomized to the mHealth group (n = 365) or the usual care group (n = 369). Women in the mHealth group had access to free, unlimited mHealth consultation services with healthcare professionals from enrollment through four months postpartum. The primary outcome of this study was the risk of elevated postpartum depressive symptoms at 12 months post-delivery (Edinburgh Postnatal Depression Scale score of ≥9). The mediation effect of alleviating loneliness on the primary outcome was also evaluated, using the UCLA loneliness scale at three months postpartum.

A total of 515 women completed the follow-up questionnaires (mHealth group, 253/365; usual care group, 262/369; 70.2% of the original participants). Compared to the usual care group, the mHealth group had a lower risk of elevated postpartum depressive symptoms at 12 months post-delivery (36/253 [14.2%] vs. 55/262 [21.0%], risk ratio: 0.68 [95% confidence interval: 0.46–0.99]). Mediation analysis showed that reducing loneliness at three months post-delivery mediated approximately 20% of the total effect of the intervention on depressive symptoms 12 months post-delivery.

mHealth consultation services provided during the early perinatal period may help alleviate depressive symptoms at 12 months postpartum.

Early life adversity (ELA) is common and cross-sectionally associated with brain gray matter structure, including cortical thickness, cortical surface area, and subcortical volumes in childhood. However, to which degree ELA influences the trajectory of gray matter macrostructural and microstructural development during childhood and adolescence remains largely unexplored.

We included 6414 participants from the Adolescent Brain Cognitive Development study at ages 9–11, where 1923 were followed to ages 11–13. We used linear mixed-effects models to test for associations between MRI-derived longitudinal measures of gray matter macro- (cortical thickness, surface area, subcortical volume) or microstructure (T1w/T2w ratio) and trauma exposure, parental acceptance, household abuse, and being resilient or susceptible to trauma in terms of developing an internalizing disorder.

At ages 9–11, higher levels of parental acceptance, trauma exposure, and being trauma resilient were associated with lower levels of cortical thickness. In contrast, being trauma susceptible was negatively related to hippocampal volume and cortical surface area. Longitudinally, more parental acceptance at baseline was associated with more cortical thinning between ages 9–11 and 11–13, while more household abuse was associated with less change in T1w/T2w ratio over time.

Parental acceptance and trauma resilience are linked to accelerated pace of apparent cortical thinning in youth aged 9–13 years, while household abuse is associated with slower microstructural development, as reflected by smaller longitudinal changes in the T1w/T2w ratio. Threat and deprivation may be distinctly associated with gray matter developmental trajectories in late childhood.

Structural brain alterations in bipolar disorder (BD) have been widely reported, yet the hierarchical organization of cortical morphometric networks and their molecular and cognitive underpinnings remain unclear.

We applied the morphometric inverse divergence (MIND) network approach to structural MRI data from 49 BD patients and 119 healthy controls. Principal MIND gradients were derived using diffusion map embedding, followed by multiscale analyses linking gradient alterations to neurotransmitter systems, cognitive-behavioral domains, and transcriptomic profiles from the Allen Human Brain Atlas. Validation was performed in three independent, cross-scanner, cross-race, and cross-age validation datasets.

Bipolar disorder patients showed significant principal gradient alterations in the left rostral middle frontal and lateral occipital cortices, with network-level decreases in the ventral attention and motor networks and increases in frontoparietal and visual networks. Gradient alterations spatially correlated with acetylcholine (VAChT) and GABA (GABAA/BZ) systems, and were associated with cognitive processes involving executive control and visual attention. Transcriptomic analyses identified gene sets enriched for BD-related GWAS loci, expressed predominantly in excitatory and inhibitory neurons, astrocytes, and oligodendrocytes, with preferential enrichment in cortical layers III-IV and developmental windows spanning early fetal to young adulthood.

These findings reveal disrupted hierarchical cortical organization in BD and link macroscale morphometric alterations to specific neurotransmitter systems and transcriptional architectures. The MIND gradient emerges as a potential biomarker bridging structural disruptions with molecular and cognitive mechanisms in BD.