To identify resilience to trauma using longitudinal psychological assessments and uncover its genetic components.

This prospective cohort study included 12,946 surgical patients from the China Surgery and Anesthesia Cohort (CSAC) with assessments of depressive symptoms from pre-surgery through 1, 6, and 12 months post-surgery, using the 9-item Patient Health Questionnaire (PHQ-9). Linear mixed-effects models predicted post-surgery PHQ-9 scores; individuals with much lower observed PHQ-9 score than expected (i.e. lowest 25th percentile of residuals) were defined as resilient. We performed genome-wide association study (GWAS) analysis to identify variants associated with psychological resilience. We examined the identified variant in 2,285 patients from the China Severe Trauma Cohort (CSTC) using genotype stratification and additive models.

CSAC participants had a mean age of 52.2 years and 58.5% were female. Overall, 2,328 (18.0%) were identified as resilient and exhibited a lower prevalence of psychological symptoms. GWAS identified a lead single-nucleotide polymorphism (rs11766511, P = 3.082 × 10−8) mapped to the gene sidekick cell adhesion molecule 1 (SDK1), as a candidate locus implicating neural signaling pathways in stress response and resilience. In CSTC, genotype stratification suggested a lower symptom burden among GG genotype of rs11766511 compared with AA carriers (e.g. Beta = −0.94 [−1.76 to −0.12] for PHQ-9 score). The additive genetic model showed a directionally consistent but non-significant protective pattern of the G allele across psychological symptoms.

Longitudinal assessments of depressive symptoms offer a reliable method for measuring psychological resilience. The rs11766511 locus mapped to SDK1 may represent a candidate genetic signal for psychological resilience and warrants confirmation.

There is growing interest in potential protective factors that may attenuate the impact of psychotic experiences (PEs), but research is still scarce. The present study investigates contemporaneous and temporal associations between daily reports of experienced stress and PEs in individuals at different early risk stages of psychosis, focusing on the possible moderating role of positive affect (PA) in these relationships (within-person moderation). Second, the buffering effect of PA differs across early risk stages (between-person moderation).

This study used 90-day daily diary data from 96 individuals allocated into 4 subgroups reflecting increasing psychosis risk: increased psychometric risk without current symptoms (subgroup 1; n = 25), low risk (subgroup 2; n = 27), mild risk (subgroup 3; n = 24), and ultra-high risk (subgroup 4; n = 20). Multilevel models, including double and triple interaction testing, applied to examine associations between experienced stress, PEs, and PA, and to compare these associations across subgroups.

Experienced stress showed a significant contemporaneous effect on PEs, which was stronger in subgroup 4 than in other subgroups and stronger in subgroup 3 compared to subgroup 1. PA significantly moderated the contemporaneous effect of experienced stress on PEs; this moderating effect did not differ between subgroups. No significant temporal effect of experienced stress on PEs was found, nor was this effect moderated by either PA or subgroups.

Experienced stress is associated with PEs contemporaneously among individuals in early risk stages, and PA buffers this association, underscoring PA as a potentially important protective factor.

Age of onset is considered a key factor for the heterogeneity in major depressive disorder (MDD). Differential cortical thickness (CT) alteration patterns between youth-onset and adult-onset MDD have been evident, yet the neurobiological factors associated with such divergence remain unknown.

CT alteration patterns in youth-onset and adult-onset MDD were derived from the Enhancing NeuroImaging Genetics through Meta-Analysis. We interrogated whether the structural connectome constrains MDD-related CT alterations, followed by identifying likely epicentre regions and examining the hub vulnerability hypothesis. Using the neurotransmitter, transcriptome, and mitochondria atlases, we further explored the neurochemical basis, genetic architecture, and molecular energetic landscape related to the CT alterations.

The structural connectome constrained CT alterations in both youth-onset and adult-onset MDD, but the constraint effect was greater in adult-onset MDD. The epicentres were divergent for youth-onset (lateral prefrontal cortex) and adult-onset (orbitofrontal cortex, anterior and middle cingulate gyrus) MDD. The association between CT alterations and connectome degree centrality confirmed the hub vulnerability hypothesis in youth-onset MDD. Moreover, we found common and distinct neurotransmitter systems linked to CT alterations in youth-onset and adult-onset MDD. Transcriptomic contextualization demonstrated that CT alterations in adult-onset MDD were related to gene categories primarily involving synapse, neuron, synaptic transmission, and ion channel activity, yet those in youth-onset MDD were not related to gene expression. Additionally, associations between mitochondrial features and CT alterations were found in adult-onset MDD but not in its youth-onset counterpart.

Our findings may illuminate the neurobiological factors related to the spatial patterning of cortical abnormalities in youth-onset and adult-onset MDD.

Children in families navigating significant adversity often face co-occurring physical and mental health problems, which together can contribute to substantial marginalization across the life course. These children and their families may greatly benefit from targeted interventions to disrupt accumulating vulnerability, which requires empirical evidence on the underlying dynamics of adversity and health problems throughout childhood.

We investigated associations between childhood adversities (material deprivation, experiences of loss or threat of loss, and family dynamics) and hospitalizations for mental and physical health problems across four developmental periods among 11,978 children who experienced high rates of family adversity. We used data from the Danish Life Course (DANLIFE) register-based cohort study and applied cross-lagged networks models. Hospitalizations were identified through inpatient, outpatient, and emergency hospital contacts.

We found clear evidence of reciprocal associations between childhood adversities and physical and mental health problems across childhood, alongside strong autoregressive effects within adversity and health domains, indicating vicious circles of reinforcing vulnerability. Conditional on high health problems in infancy, childhood adversity was not found to be associated with additional health problems throughout the rest of childhood. Child health problems were, however, positively associated with subsequent adversity across childhood.

Dynamics of childhood adversity and poor health give rise to complex reinforcing patterns of vulnerability over time. Our findings contribute to a better understanding of the emergence of vulnerability resulting from childhood adversity and poor health in children, highlighting the importance of embracing the complex nature of these emergent phenomena, both in research and intervention.

Identifying how affect and daily behaviors influence each other is central to understanding mood disorder development. This study investigated how negative affect (NA), positive affect (PA), physical activity, and smartphone use influence one another in daily life, and whether familial risk or mood disorder history shapes these relationships.

In a 14-day experience sampling protocol, we measured NA and PA five times a day along with passive sensing of step count and screen-on time. We examined the effect of familial high risk and history of mood disorders on within-person affect–behavior dynamics using Dynamic Structural Equation Modeling.

The sample included offspring of parents with bipolar disorder (n = 82) and control participants (total n = 128, Mage = 37.8, 57% female), of which 32 had a history of mood disorders (recurrent: n = 3, single: n = 29). Results showed a credible bidirectional relationship between step count and PA (step count → PA: β = 0.06; 95% credibility interval [CrI], 0.02–0.09; PA → step count: β = .07; 95% CrI, 0.03–0.11), while NA exhibited no credible associations. Higher PA predicted decreased screen-on time (β = −.05; 95% CrI, −0.08 to −0.02), while increased screen-on time was associated with subsequent elevated NA (β = .03; 95% CrI, 0.01–0.06). Familial risk status and recurrent mood disorders did not alter these bidirectional effects, but were associated with lower PA and higher NA on average (all p < 0.001).

Findings highlight PA as a key driver in the interplay between behavior and affect. Supporting PA through increased activity may help improve daily emotional experiences, even in those with elevated mood disorder risk.

Adults with a history of childhood trauma often experience impairments in social cognition, but these difficulties are rarely therapeutically targeted. We designed ‘SOCIAbLE’ as a novel virtual reality (VR)-assisted intervention to improve social cognitive functioning and real-world social function in adults with childhood trauma histories.

This single-arm proof-of-concept study evaluated the feasibility, acceptability, and preliminary outcomes of the SOCIAbLE intervention. Adults with a history of early-life adversity and ongoing social difficulties completed eight weekly one-hour intervention sessions combining psychoeducation, cognitive-behavioral strategies, and immersive VR role-play, targeting social cognition. Outcome assessments were conducted at baseline, 6, 12 (end of treatment), and 18 weeks. Acceptability was assessed based on post-intervention qualitative interviews.

Of 32 participants who completed baseline, n = 25 completed the full 8-week intervention; n = 23 completed the 12-week intervention, and n = 24 completed the 18-week follow-up assessments. Improvements relative to baseline were observed at 12 weeks on both our primary (BLERT emotional recognition: g = 1.04) and secondary outcome measures, which persisted at 18 weeks. Data from qualitative interviews (n = 24) indicated a high level of intervention acceptability to participants, highlighting perceived gains in confidence, self-awareness, and real-world social functioning.

In this pilot study, SOCIAbLE was observed to be feasible and acceptable and showed preliminary evidence of benefits to social cognition, clinical symptoms, and social functioning. These data suggest that immersive VR-assisted interventions warrant further investigation in a full randomized controlled trial as a potentially effective, engaging way to target social cognitive difficulties in adults with a history of CT.

Gambling disorder (GD) is clinically heterogeneous, with trait impulsivity and negative affect (anxiety/depression) representing key sources of variation. This study investigated whether neurophysiological responses to loss feedback differ across GD subgroups defined by these features and whether subgroup membership moderates the association between neural responses and clinical severity.

Electroencephalography was recorded from 120 individuals with GD, typed via k-means clustering of impulsivity, anxiety, and depression scores, and 52 healthy controls (HC) during the Balloon Analogue Risk Task. Event-related potentials, including feedback-related negativity (FRN) and P3, were used to index feedback processing.

Two GD subgroups were identified: an ‘impulsive type’ (high impulsivity, low negative affect) and an ‘emotionally vulnerable type’ (high impulsivity with severe anxiety/depression), with the latter exhibiting greater gambling severity. Neurophysiologically, the emotionally vulnerable type showed blunted FRN and feedback-P3 amplitudes to loss feedback compared to HC, whereas the impulsive type did not differ from HC. Critically, subgroup membership moderated the association between feedback-P3 and gambling severity; a reduced feedback-P3 predicted higher severity only within the emotionally vulnerable type.

These findings identify blunted neural responses to loss feedback as a specific characteristic of the emotionally vulnerable GD type. These findings resolve the inconsistent patterns of loss feedback processing in GD and highlight the potential for personalized interventions targeting this subgroup.

Perinatal depression is a global health concern linked to adverse maternal and neonatal outcomes. Although evidence-based psychological interventions, such as interpersonal psychotherapy (IPT), are effective, women lack access to in-person perinatal care. Smartphone-based interventions may offer scalable support; however, evidence from randomized controlled trials (RCTs) evaluating IPT-informed smartphone interventions remains limited. This study assessed the acceptability and efficacy of an IPT-informed smartphone intervention for perinatal mental well-being.

Participants were recruited nationwide through online advertisements and postcards. In this nonblinded RCT, 350 pregnant women were assigned to a fully self-guided smartphone application (intervention) or usual care (control). No minimum depression symptom score was required for participation. Acceptability in the intervention group at 8 weeks after enrolment was indicated by the Japanese version of the Client Satisfaction Questionnaire-8 (CSQ-8J) scores of ≥17. Efficacy was defined as the change in Patient Health Questionnaire-9 (PHQ-9) scores from baseline to 8 weeks following enrolment. Depressive symptoms were assessed at 1 month postpartum.

The application achieved acceptability, with 90.2% (157/174) of participants scoring ≥17 on the CSQ-8J. No significant between-group differences in depressive symptoms were observed during pregnancy (standardized mean difference (SMD) = 0.11). At 1 month postpartum, the intervention group exhibited significantly lower depressive symptom scores (SMD = 0.28).

The smartphone application was highly acceptable. While no significant differences in depressive symptoms were observed during pregnancy, differences favoring the intervention group were observed at 1 month postpartum. An IPT-informed smartphone intervention may represent a promising approach to perinatal mental health support.

Cerebral perfusion abnormalities may contribute to the pathophysiology of psychosis spectrum disorders (PSD), including schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar disorder with psychotic features (BP), yet large-scale investigations remain limited.

Pseudo-continuous arterial spin labeling scans were acquired from 2412 SZ, 2278 SAD, 158 BP, 401 neurotypical controls (NC) and processed using ExploreASL and FreeSurfer to quantify resting-state cerebral blood flow (CBF) across total gray matter and 60 brain regions. General linear regression compared CBF between NC and diagnostic groups or biologically informed biotypes derived from neurophysiological clustering. Within patient groups, Spearman correlations assessed associations between cognitive/clinical measures and CBF. Analyses were corrected for multiple comparisons.

Compared to NC, patient groups showed significantly lower total gray matter CBF (PSD: Cohen’s d=-0.124, p-adjusted=0.037; BP: d=-0.259, p-adjusted=0.004; the most severe biotype, Biotype 1: d=-0.222, p-adjusted=0.006). BP and Biotype 1 exhibited significant hypoperfusion in 25 regions spanning bilateral temporal, occipital, inferior frontal cortices, and subcortical structures (BP d= -0.21 to -0.33; Biotype 1 d=-0.19 to -0.26). No significant CBF-cognition associations were observed. Within PSD, higher total gray matter CBF correlated with greater psychotic symptom severity, while right superior temporal sulcus hyperperfusion was associated with greater psychotic, manic, and depressive symptoms.

Distinct perfusion patterns exist in PSD, with widespread hypoperfusion in BP and Biotype 1 and hyperperfusion associated with greater symptom severity, supporting perfusion as a potential biomarker to stratify PSD subtypes.

Suicidal ideation among youth is a public health crisis, creating a need to identify features that can prognosticate suicide-related outcomes. This study characterized trajectories of suicidal thoughts in youth with depression/suicidality and evaluated features predicting trajectories.

Participants in the Texas Youth Depression and Suicide Research Network with self-reported suicidal ideation data available for baseline and ≥2 other time points were included (n = 1,449). Group mixture models were used to identify trajectories of suicidal thoughts at four follow-up assessments during the succeeding 6 months. Random Forest analyses evaluated baseline clinical and sociodemographic variables that predicted trajectory group membership after splitting into training (two-thirds) and validation (one-third) samples.

Mean (standard deviation) age was 15.6 (2.7) years, and 72.8% were female. Three trajectories were identified: persistently no (43.3%), persistently low (44.2%), and persistently high (12.4%) suicidal thoughts. In Random Forest analyses, self-reported severity of suicide propensity (including pessimism, helplessness, perceived lack of social support, and despair) plus a clinical interview of suicidal ideation predicted these trajectories. The area under the curve in training and validation samples for predicting persistently no suicidal thoughts was 0.83 and 0.80, respectively, and for persistently high suicidal thoughts was 0.87 and 0.87, respectively.

Three distinct trajectories of suicidal thoughts were identified. A combination of baseline self-reported measures of depression, pessimism, helplessness, perceived lack of social support, and despair, along with a clinical interview of suicidal ideation, predicted no or high suicidal thoughts over 6 months with high accuracy, providing a clinically useful predictive model of suicide risk.

Major depressive disorder (MDD) is a complex disorder caused by genetic and environmental factors. Previous evidence implicates a potential depression subtype from interaction between childhood maltreatment (CM) and kynurenine pathway (KP) gene. Here, we investigated the top-down multi-omics KP alterations for this subtype.

A total of 142 patients with MDD receiving monotherapy were included. Individuals carrying IDO2 rs2340953 TT genotype and reporting CM were classified as IDO2-CM group, whereas the remaining patients were categorized as non-IDO2-CM group. Plasma KP metabolites, DNA methylation, KP-related protein, and inflammatory protein were profiled. Group differences were examined using regression models adjusting for relevant covariates.

Thirty patients met criteria for the IDO2-CM group. Compared with non-IDO2-CM, IDO2-CM individuals exhibited significantly poorer response rate to antidepressant at weeks 4 and 8. Metabolite analyses revealed a significantly elevated quinolinic acid (QA)/kynurenine (KYN) ratio and QA/kynurenic acid (KYNA) ratio in IDO2-CM group (β = 0.086, SE = 0.042, P = 0.023; β = 0.164, SE = 0.045, P = 0.0006). Epigenetic analyses of KP genes demonstrated coordinated methylation shifts favoring QA production (hypomethylation of KMO and AFMID; hypermethylation of ACMSD) and suppression of KYNA related enzymes (hypermethylation of CCBL1, CCBL2, AADAT, and GOT2). Proteomic profiling identified reduced circulating levels of KYNU and VCAM1 in IDO2-CM group.

CM interacting with IDO2 genotype defines a biologically distinct MDD subtype characterized by poor antidepressant response and convergent multi-omics evidence of KP bias toward neurotoxic metabolism. These findings support a stratification strategy and highlight the KP as a potential target for precision treatment in depression.

Poor school achievement in comprehensive education (~ age 15) has been associated with the later risk of mental disorders, but it remains unclear whether school achievement in upper secondary education (~ age 18) is also associated with this risk. We examined whether school achievement in upper secondary education is associated with the later risk of mental disorders and whether school achievement in comprehensive education modifies these associations.

We studied all individuals born in Finland between 1980 and 2001 (N = 579 781). Individuals were followed from graduation from upper secondary education (ages 18–20) until first mental disorder diagnosis, emigration, death, or December 31, 2023. Matriculation examination grade point average (GPA) at the end of upper secondary education was the main exposure. Time to a mental disorder diagnosis was the outcome. Associations were estimated using Cox proportional hazards models, including sibling-stratified analyses and stratification across comprehensive education GPA groups.

Upper secondary GPA showed no consistent association with any mental disorder diagnosis as a broad category. Greater upper secondary GPA was generally associated with smaller risk of substance use disorders and greater risk of depression, anxiety, eating, and personality disorders. Reduction in GPA from comprehensive to upper secondary education was associated with greater risk of schizophrenia, and improvement with greater risk of bipolar disorder.

Associations between school achievement in upper secondary education and later mental disorders are disorder-specific, with higher school achievement associated with either an increased or decreased risk depending on the specific disorder.

Prior research shows that humans adjust their learning rate based on environmental volatility. This adaptation has been shown to be reduced in individuals with high levels of anxious-depression, but past studies have been cross-sectional, making it unclear whether this adaptation is trait-like or responsive to treatment. There are also questions about the basic replicability of this effect with recent studies failing to find robust associations.

In the Precision in Psychiatry study, we examined changes in learning rate adaptation in a points-loss task, following four weeks of treatment in two patient groups receiving either internet-based cognitive behavioral therapy (n = 677) or antidepressants (n = 95), compared to a group of healthy participants (n = 95).

All groups showed increased learning rates in volatile environments at baseline, but against our prediction, learning rate adaptation was not cross-sectionally associated with individual differences in anxious-depression. There was also no evidence that learning rate adaptation changed post-treatment, despite symptom improvements. However, in the antidepressant group, symptom reductions correlated with learning rate adaptation. This finding should be interpreted cautiously as we found that the key outcome measure had poor test–retest reliability.

Overall, our results suggest that associations between learning rate adaptation and anxious-depression, if present, are likely modest, depend on task characteristics, may not be present in treatment-seeking adults, and do not improve following treatment.