Psychological Medicine[JOURNAL]
Sun
200 papers
Computerized assessments of emotional expression and emotional reactivity predict negative symptoms in individuals at clinical high-risk for psychosis.
Bertrand CE, Pokorny VJ, Gold JM … +11 more , Waltz JA, Schiffman J, Ellman LM, Strauss GP, Walker EF, Woods SW, Powers AR, Kenney J, Corlett PR, Silverstein SM, Mittal VA
Psychol Med · 2026 Jun · PMID 42267441 · Full text
BACKGROUND: Negative symptoms are a core feature of psychosis and a strong predictor of functional outcome, yet they remain difficult to assess due to conceptual and methodological challenges. Although abnormalities in e...
BACKGROUND: Negative symptoms are a core feature of psychosis and a strong predictor of functional outcome, yet they remain difficult to assess due to conceptual and methodological challenges. Although abnormalities in emotional expressivity and emotional reactivity are documented in individuals at clinical high-risk (CHR) for psychosis, these domains are typically examined independently, and their relationship remains unclear. METHODS: Facial expressions were quantified using automated facial analysis (FaceReader) during clinical interviews in 101 CHR individuals and 41 healthy controls (HCs). Emotional reactivity was assessed using the International Affective Picture System (IAPS). Principal component analyses were conducted on facial expression and emotional reactivity variables within the CHR group. Associations with negative symptom domains, positive symptoms, and social functioning were examined using correlational and two-step regression analyses. RESULTS: CHR participants showed greater disgust expression than HCs (g = 0.40, uncorrected = .0025, FDR-corrected = .023). Facial expression and emotional reactivity components showed minimal associations ( > .20). Reduced high-arousal facial expressions were associated with greater emotional expressivity deficits ( = -.22, = .027), whereas greater happy facial expression was associated with more motivation and pleasure impairment ( = .21, = .044). Happy facial expression explained additional variance in motivation symptoms beyond emotional reactivity (Δ = .089, = .008). CONCLUSIONS: Automated facial expression captured variance in some negative symptom domains that was largely independent of emotional reactivity. These findings support the use of multimodal, objective assessments to improve characterization of negative symptoms in psychosis risk.
Network functional connectivity and anterior cingulate cortex gamma-aminobutyric acid in antipsychotic medication-naïve first-episode psychosis patients.
Samson GD, Maximo JO, Nelson E … +3 more , Adnani SN, Bashir A, Lahti AC
Psychol Med · 2026 Jun · PMID 42261240 · Full text
BACKGROUND: Functional connectivity (FC) is consistently altered in patients with schizophrenia. The brain's primary inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), and its relationship to FC in psychosis sp...
BACKGROUND: Functional connectivity (FC) is consistently altered in patients with schizophrenia. The brain's primary inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), and its relationship to FC in psychosis spectrum disorders are under-investigated. The anterior cingulate cortex (ACC) has been implicated in many cognitive functions impaired in psychosis. We hypothesize that the relationships between ACC GABA and FC in key brain networks will be altered in first-episode psychosis (FEP) patients as compared to healthy controls (HC). METHODS: We used magnetic resonance spectroscopy (MRS) with a MEGA-PRESS sequence to quantify ACC GABA levels in 67 antipsychotic medication-naïve FEP patients and 110 HC. Resting state functional magnetic resonance imaging (fMRI) was used to assess positive and negative FC within the default mode (DMN), salience (SN), dorsal attention (DAN), and executive control (ECN) networks. We used linear regressions to test GABA-FC relationships in each network between groups. RESULTS: FEP patients had significantly lower GABA levels compared to HC. We also found several clusters in the ECN, DAN, and DMN where FC differed between groups. Ultimately, we found significant GABA-FC group interactions in two ECN clusters and one SN cluster, where GABA and FC were positively correlated in HC but negatively correlated in FEP. CONCLUSIONS: Our data add to the growing literature supporting GABA's significant role in psychosis spectrum disorders, especially as it relates to FC in key brain networks. Our findings call for further investigation of the mechanisms underlying altered neurometabolic activity and connectivity in psychosis spectrum disorders.
Methodological guidance on clinical prediction models in mental health research.
Costa R, de Sousa B, Kneib T … +2 more , Martins R, Mayr A
Psychol Med · 2026 Jun · PMID 42261225 · Full text
Clinical prediction models play a crucial role in advancing personalized care for mental health disorders, providing essential insights for diagnosis, prognosis and intervention planning. This work examines the current m...
Clinical prediction models play a crucial role in advancing personalized care for mental health disorders, providing essential insights for diagnosis, prognosis and intervention planning. This work examines the current methodological approaches used to develop such models, emphasizing their application to mental health problems, including depression. To illustrate these concepts, we used data on prenatal depression from a multinational observational study of 5,372 pregnant women. The goal is to develop an individual prognostic model for depressive symptoms that can be used already at the beginning of pregnancy. Our analysis explores variable selection strategies, validation methodologies and the integration of clinical expertise with data-driven approaches. Particular attention is given to addressing challenges such as population heterogeneity, overfitting and the importance of external validation for generalizability across diverse settings. We distinguish between statistical regression models and machine learning techniques, discussing their respective strengths and limitations in terms of interpretability, predictive accuracy and clinical usability. This work offers practical guidance for researchers and clinicians, focusing on the critical steps for model development and implementation. We highlight best practices to avoid common pitfalls, advocate for interdisciplinary collaboration and address challenges of integrating advanced statistical and machine learning tools into clinical practice. By providing practical guidance and addressing these issues, our aim is to support the development of robust and clinically relevant prediction models.
Strengths-based resilience: the biopsychosocial factors that differentiate 12-year mental well-being trajectories following adverse childhood experiences.
Connon E, Park HRP, Turner RM … +2 more , Williams LM, Gatt JM
Psychol Med · 2026 Jun · PMID 42260997 · Full text
BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased long-term mental and physical health risk, yet inter-individual variation indicates that resilience is possible. Distinct trajectories of sus...
BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased long-term mental and physical health risk, yet inter-individual variation indicates that resilience is possible. Distinct trajectories of sustained mental well-being have been observed among individuals exposed to ACEs, predicting favorable long-term outcomes. However, the biopsychosocial markers underpinning sustained trajectories of resilience remain poorly understood. This study aimed to identify factors that predict higher well-being ('resilient') trajectories over time in individuals with and without ACE exposure. METHODS: Previously identified 12-year well-being trajectory classes (higher vs. lower well-being) were examined in participants with no ACE history ( = 779) and those exposed to ACEs ( = 889). Logistic regression models were used to identify factors differentiating higher versus lower well-being trajectories in the non-ACE sample, and resilience versus risk trajectories in the ACE sample. Predictors included childhood adversity characteristics, genetic predisposition, demographic and environmental factors, social and occupational factors, health and lifestyle factors, and psychological functioning. RESULTS: Across both samples, higher well-being was predicted by higher education, better subjective physical health, greater social engagement, stronger work performance, and adaptive personality traits (lower neuroticism and higher extraversion). In the non-ACE sample, polygenic well-being scores and family history of mental illness further differentiated trajectories. In contrast, resilience following ACEs was additionally characterized by modifiable factors, including parenting style, relationship status, BMI, and conscientiousness. CONCLUSIONS: Resilience in the context of childhood adversity is defined by identifiable, largely modifiable social, health, and personality factors, highlighting potential targets for interventions to enhance long-term well-being.
The long reach of childhood income inequality: a multinational twin study of gene-environment interplay on adult depressive symptoms.
Petkus AJ, Reynolds CA, Finch BK … +18 more , Thomas K, Beam CR, Catts VS, Ericsson M, Finkel DG, Franz CE, Kremen WS, Larsen LA, Martin NG, McGue M, Mosing MA, Neiderhiser JM, Nygaard M, Pedersen NL, Thalamuthu A, Whitfield KE, Gatz M, IGEMS Consortium
Psychol Med · 2026 Jun · PMID 42253158 · Full text
BACKGROUND: Living in a country with a large gap between high and low earners has been linked to poor health, including depression. Less studied is gene-by-environment interplay with income inequality as the environmenta...
BACKGROUND: Living in a country with a large gap between high and low earners has been linked to poor health, including depression. Less studied is gene-by-environment interplay with income inequality as the environmental exposure. Here, we examine the association between childhood exposure to inequality and individual differences in adult depressive symptoms, testing for moderation of genetic influences by inequality using polygenic indices for major depressive disorder, as well as twin models. METHODS: The research participants were 69,924 members of twin studies from four developed countries, born between 1893 and 1979, aged 22-103 years at depressive symptom assessment. Genotyping was available for 6,256 participants. Income inequality was operationalized as share of income accruing to the top 1% for each country when the participants were between age 5 and 15 years. RESULTS: Childhood income inequality was associated with depressive symptom scores in adulthood, adjusting for covariates. Each 1% rise in inequality was associated with 0.295 higher depressive symptoms (scaled on T-score units). In genetic analyses, interaction effects showed that men who faced more inequality as children and had higher genetic risk for depression reported modestly higher depressive symptoms compared to other men. For women, both genetic risk and inequality mattered, with each independently associated with depressive symptoms. Twin models showed that inequality moderated genetic variance underlying depressive symptoms; heritability of depressive symptoms was higher where exposure to income inequality was higher. CONCLUSIONS: Findings illustrate the long reach of childhood exposure to income inequality and suggest that advantaged environments may help protect against the effects of deleterious genes.
Antidiabetes agents and risk of incident depression in 686,522 people with type 2 diabetes mellitus: A 20-year population-based cohort study.
Ho MTH, Chan JKN, Lo HKY … +7 more , Fang CZ, Wong CSM, Lee KCK, Lai FTT, Ng APP, Wong WCW, Chang WC
Psychol Med · 2026 Jun · PMID 42253148 · Full text
BACKGROUND: People with diabetes have increased risk of depression that further worsens clinical outcome. However, occurrence of depression among patients with diabetes exposed to antidiabetes agents is under-studied. We...
BACKGROUND: People with diabetes have increased risk of depression that further worsens clinical outcome. However, occurrence of depression among patients with diabetes exposed to antidiabetes agents is under-studied. We investigated whether antidiabetes agents would decrease the risk of depression in people with diabetes. METHODS: This population-based cohort study identified 686,522 patients with incident type-2 diabetes between 2002-2021 in Hong-Kong who were exposed to any antidiabetes agents, using territory-wide medical-record database of public-healthcare services. Associations of exposure to antidiabetes agents and risk of first-diagnosed depression were examined by Cox proportional-hazards models for each individual agent. An array of covariates, including age, sex, calendar-year period, catchment-area, pre-existing physical/psychiatric-comorbidities, average HbA1c-level, diabetic-complications, cardiovascular/lipid-lowering medications, and presence of other antidiabetes agents under investigation was adjusted. Three sets of sensitivity-analyses were conducted by (a) restricting to patients with cumulative drug-exposure ≥90 days and ≥180 days, (b) monotherapy, and (c) incorporating commonly-used non-antidiabetic medications as exposure variables. RESULTS: Lower risk of new-onset depression was associated with exposure to any antidiabetes agents (HR 0.42, 95%CI 0.39-0.45) compared with no exposure in patients with incident type-2 diabetes. Lower depression risk was associated with exposure to metformin (0.61[0.57-0.66]) compared with no antidiabetes agents, and to pioglitazone (0.25[0.10-0.63]), linagliptin (0.26[0.13-0.52]), and insulin (0.63[0.55-0.72]). Sensitivity-analyses affirmed that lower depression risk was associated with metformin and insulin. CONCLUSION: Patients with type-2 diabetes with exposure to several antidiabetes agents is at decreased risk of new-onset depression. Further research is warranted to clarify the depression-reducing mechanisms of antidiabetes agents in this vulnerable population.
Psychological and behavioral mechanisms linking childhood trauma profiles to voice-related distress in schizophrenia spectrum disorders: latent class, mediation, and conditional process analyses.
Christensen MJ, Olesen AV, Ward T … +8 more , Hardy A, Mainz J, Thomas N, Smith LC, Mariegaard LS, Nordentoft M, Glenthøj LB, Vernal DL
Psychol Med · 2026 Jun · PMID 42253147 · Full text
BACKGROUND: Childhood traumas increase the risk of psychosis and voice-hearing. While trauma profiles have been identified in voice-hearers, pathways linking these to voice-related distress remain unclear. This study exa...
BACKGROUND: Childhood traumas increase the risk of psychosis and voice-hearing. While trauma profiles have been identified in voice-hearers, pathways linking these to voice-related distress remain unclear. This study examined between-group differences in mediation by psychological and behavioral variables in profile-distress associations, with potential moderation by gender. METHODS: This cross-sectional study derived childhood trauma profiles via latent class analysis of Childhood Trauma Questionnaire (CTQ) scores from 266 voice-hearing Challenge trial participants with schizophrenia-spectrum diagnoses. Mediation analyses (structural equation modeling with bootstrapped 95% confidence intervals for indirect effects) tested between-group differences in indirect effects of negative voice content, persecutory beliefs about voices, voice power, voice relating style, negative self/other beliefs, emotion regulation, depression, and sleep disturbances in the association between childhood trauma profiles (exposure) and voice-related distress (outcome), with gender as a moderator. Hypotheses were preregistered on the Open Science Framework. Reporting followed AGReMA-guidelines. RESULTS: Three childhood trauma profiles were established: (1) 'variable severity' ( = 160), (2) 'severe neglect and emotional abuse' ( = 84), and (3) 'severe poly-trauma' ( = 22). Significant between-group differences in indirect effects were observed for persecutory beliefs about voices (1 < 3), voice power (1 < 3), and sleep disturbances (1 < 2). Age-adjustment revealed a between-group difference in indirect effect of negative self-beliefs (1 < 3). No moderation by gender was found. CONCLUSIONS: This is the first investigation of mediators and moderators of childhood trauma profiles and voice-related distress in clinical voice-hearers. Findings suggest that trauma profiles may provide indicators of mediators potentially relevant to inform individualized formulation and therapy planning.
Disrupted brain functional networks in adolescents and young adults with gaming disorder during social interaction: An fNIRS study.
Wang Z, Huang C, Shan H … +14 more , Wang Y, Li S, Guo L, Lyu X, Chen Y, Zeng Y, Su H, Chen T, Du J, Jiang H, Deng M, Wen X, Zhao M, Zhong N
Psychol Med · 2026 Jun · PMID 42253034 · Full text
BACKGROUND: Gaming disorder (GD) is increasingly recognized for its adverse impact on social functioning, yet the underlying neural mechanisms remain unclear, particularly during real-time social interactions. This study...
BACKGROUND: Gaming disorder (GD) is increasingly recognized for its adverse impact on social functioning, yet the underlying neural mechanisms remain unclear, particularly during real-time social interactions. This study examined neural differences in the prefrontal cortex (PFC) and temporoparietal junction (TPJ) during cooperation and competition tasks in adolescents and young adults with GD. METHODS: Using functional near-infrared spectroscopy (fNIRS), we examined 175 male participants, classified into Gaming Disorder (n = 42), Hazardous Gaming (n = 69), and Healthy Control (n = 64) groups. Participants performed cooperation and competition tasks while activation, functional connectivity, and network topology were assessed within the PFC and TPJ. RESULTS: In the current study, GD participants exhibited significantly greater impairments in social and emotional functioning compared to the HG and HC groups. The GD group showed increased right TPJ activation during cooperation and decreased activation during competition. Both GD and HG groups demonstrated heightened medial PFC activation and functional connectivity, indicating compensatory engagement. Graph theory analysis revealed disrupted network topology in GD, including reduced nodal efficiency and centrality within the PFC and TPJ. Neural alterations were significantly correlated with clinical measures, including gaming duration and social-emotional deficits. CONCLUSION: This study identifies critical neural disruptions underlying social dysfunction in GD, particularly within mentalizing and executive control networks. The neural markers observed in the GD group have important implications for clinical diagnosis and targeted intervention, whereas similar patterns in the HG group highlight opportunities for early detection and preventive strategies.
Determining the relative importance of risk and protective factors for adjustment disorder symptoms during the COVID-19 pandemic by mixed-effects random forests.
Lotzin A, Finne E, Schildbach G … +23 more , Acquarini E, Ajdukovic D, Ajdukovic M, Anastassiou-Hadjicharalambous X, Ardino V, Hensler I, Arnberg FK, Böttche M, Dragan M, Figueiredo-Braga M, Gelezelyte O, Grajewski P, Groen S, van Hoof MJ, Javakhishvili JD, Kazlauskas E, Lioupi C, Lueger-Schuster B, Sales L, Tsiskarishvili L, Zrnic Novakovic I, Schäfer I, ADJUST Study Consortium
Psychol Med · 2026 Jun · PMID 42237604 · Full text
BACKGROUND: The COVID-19 pandemic exposed individuals to numerous psychosocial and health-related stressors associated with adjustment disorder (AjD) symptoms, yet it remains unclear which factors are most predictive. ME...
BACKGROUND: The COVID-19 pandemic exposed individuals to numerous psychosocial and health-related stressors associated with adjustment disorder (AjD) symptoms, yet it remains unclear which factors are most predictive. METHODS: Using mixed-effects regression random forests (MERF), a machine learning approach that combines random forests with mixed-effects regressions, we analyzed longitudinal data from 15,155 adults across 11 European countries collected at three time points between June 2020 and January 2022. We evaluated 245 candidate predictors, including sociodemographic, pandemic-related, and health-related factors, for their relative importance in predicting AjD symptoms (ADNM-8). RESULTS: The seven most influential predictors, ranked in descending order of importance, were uncertainty about the pandemic's duration and risks, poor health, social isolation, conflicts at home, loss of daily structure, fear of infection, and restricted personal contact with close others. CONCLUSIONS: AjD symptoms were most strongly linked to factors related to lack of control (e.g., uncertainty, loss of daily structure, fear of infection), as well as current poor health and reduced social connectedness. Interventions that enhance a sense of control through clear communication, help individuals re-establish daily routines, and strengthen social connectedness may mitigate AjD symptoms during future public health crises. Our findings also highlight the potential of machine learning approaches for identifying complex patterns across high-dimensional predictors of clinical symptoms, which may improve prediction accuracy in mental health research.
Cell-type and spatiotemporal transcriptional signatures of white matter morphometric similarity network alterations in major depressive disorder.
Wu Y, Xu J, Wang H … +11 more , Shen Y, Zhai Y, Lei M, Zhang Z, Wu Q, An Q, Cai W, Su L, Peng Y, Zhang Q, Liu F
Psychol Med · 2026 Jun · PMID 42237602 · Full text
BACKGROUND: White matter (WM) abnormalities are implicated in major depressive disorder (MDD), yet the organization of white matter morphometric similarity networks (WM-MSNs) - which capture interregional similarity in v...
BACKGROUND: White matter (WM) abnormalities are implicated in major depressive disorder (MDD), yet the organization of white matter morphometric similarity networks (WM-MSNs) - which capture interregional similarity in voxel-wise WM morphology - and the transcriptional mechanisms associated with their disruption remain insufficiently understood. METHODS: Using T1-weighted MRI from a large multisite sample (1,154 individuals with MDD and 1,026 healthy controls), we constructed individualized WM-MSNs. Group differences were assessed at the edge, global, and nodal levels. To identify molecular pathways underlying these alterations, nodal abnormalities were linked to regional gene expression profiles from the Allen Human Brain Atlas using spatially informed transcriptomic association, followed by functional, cell-type-specific, and developmental enrichment analyses. RESULTS: MDD showed distributed but selective reorganization of WM-MSNs. Network-based statistics revealed two significant components, with 118 edges exhibiting increased morphometric similarity and 45 showing decreased similarity. Globally, MDD demonstrated higher small-worldness, clustering coefficient, global efficiency, and local efficiency, together with shorter characteristic path length. Nodal disruptions were concentrated in major commissural and association tracts - including the corpus callosum, cingulum, uncinate fasciculus, and tapetum. Transcriptomic integration indicated enrichment for gene signatures related to oligodendrocyte function, myelination, lipid metabolism, axonal organization, and cellular stress-related molecular processes, with implicated genes showing broad developmental-stage expression. CONCLUSIONS: MDD is associated with robust alterations in individualized WM-MSNs that converge with transcriptional signatures linked to myelination, metabolic processes, axonal structure, and cellular stress, linking macroscale network disruption to underlying molecular architecture and providing cross-scale insights into WM pathology in depression.
Modulation of depression through the neurobiological underpinnings of the glymphatic-rumination relationship.
Ma J, Zhang R, Lin K … +1 more , Lee TMC
Psychol Med · 2026 Jun · PMID 42237463 · Full text
BACKGROUND: Glymphatic functioning is implicated in cognitive and affective functioning. Given that rumination, a major risk factor for major depressive disorder (MDD), is a cognitive process regulating information proce...
BACKGROUND: Glymphatic functioning is implicated in cognitive and affective functioning. Given that rumination, a major risk factor for major depressive disorder (MDD), is a cognitive process regulating information processing, knowledge of the neurobiological mechanisms underpinning the relationship among glymphatic functioning, rumination, and depression would offer significant insight into the precipitating and maintenance mechanisms of MDD. METHODS: This study recruited 53 MDD patients and 47 matched healthy controls (HCs). Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index was computed as a proxy of the glymphatic functioning. Rumination and depressive severity were evaluated using Ruminative Response Scale (RRS) and Hamilton Depression Rating Scale (HAMD), respectively. Static and dynamic functional connectivity (FC/dFC) analyses were performed, and associations with neurotransmitter maps were explored. RESULTS: MDD patients showed reduced glymphatic function compared to HCs, with lower glymphatic function correlating with more severe depression and rumination. Rumination mediated the glymphatic-depression relationship. Furthermore, overlapping static FC involving default mode and subcortical networks linked the glymphatic functioning and rumination. Edge-centric dynamic FC analysis showed reduced State 3 occurrence and heightened rumination, further mediating the glymphatic-rumination relationship in HCs. Both FC biomarkers spatially correlated with various neurotransmitter maps (e.g. dopamine). CONCLUSIONS: Glymphatic dysfunction may exacerbate depression by disrupting brain networks and neurotransmitter balance, trapping individuals in maladaptive rumination. Enhancing glymphatic flow (e.g. via physical exercise) could restore neurobiological health, breaking the maladaptive cycles. This highlights glymphatic functioning as a potential therapeutic target bridging neurobiology, cognition, and depression severity.
Safety behaviors maintain persecutory ideation in individuals with psychotic disorders: evidence from an ecological momentary assessment study.
Schönig SN, Lincoln TM, Krkovic K
Psychol Med · 2026 Jun · PMID 42231752 · Full text
BACKGROUND: Safety behaviors are a common response to persecutory ideation in psychosis. They potentially contribute to the maintenance and exacerbation of symptoms and emotional distress and are therefore a promising tr...
BACKGROUND: Safety behaviors are a common response to persecutory ideation in psychosis. They potentially contribute to the maintenance and exacerbation of symptoms and emotional distress and are therefore a promising treatment target. However, empirical evidence for this hypothesized maintenance role is scarce. We therefore examined cross-sectional and micro-longitudinal associations between safety behaviors, negative affect, and persecutory ideation in the daily lives of individuals with psychotic disorders. METHODS: We assessed safety behaviors, persecutory ideation, and negative affect at baseline and 10 times/day during one week of Ecological Momentary Assessment (EMA) in = 64 participants with persecutory ideation and a psychotic disorder. RESULTS: At baseline, safety behaviors were positively correlated with persecutory ideation ( = .47), depression ( = .67), and anxiety ( = .69). Safety behaviors assessed at baseline and safety behaviors assessed in daily life showed a moderate correlation ( = .56). Multilevel analyses of the longitudinal EMA data revealed persecutory ideation ( = .16) and negative affect ( = .11) to predict subsequent use of safety behaviors. Momentary use of safety behaviors predicted subsequent persecutory ideation ( = .13) and negative affect ( = .18). CONCLUSIONS: Our results provide evidence for a vicious cycle of maintenance involving persecutory ideation, negative affect, and safety behaviors. Targeting safety behaviors with ecological momentary interventions in daily life could be a promising approach to interrupt this cycle.
Polygenic risk factors for comorbid diagnoses in individuals with substance use disorders: A phenome-wide survival analysis.
Barr PB, Neale ZE, Bigdeli TB … +4 more , Chatzinakos C, Harvey PD, Peterson RE, Meyers JL
Psychol Med · 2026 Jun · PMID 42219759 · Full text
OBJECTIVE: Persons with substance use disorders (SUD) often suffer from additional comorbidities. Researchers have explored this overlap via phenome-wide association studies (PheWASs). However, PheWASs are largely cross-...
OBJECTIVE: Persons with substance use disorders (SUD) often suffer from additional comorbidities. Researchers have explored this overlap via phenome-wide association studies (PheWASs). However, PheWASs are largely cross-sectional, limiting our understanding of whether diagnoses predate the development of an SUD. We characterize whether polygenic scores (PGSs) are associated with time to comorbid diagnoses in electronic health records (EHR) after the first documented SUD diagnosis. METHODS: Using data from All of Us ( = 393,596), we explored: (1) whether social determinants of health (SDoHs) are associated with lifetime risk of SUD ( cases = 42,568) and (2) within a subset those with a diagnosed SUD and available genetic data SUD ( = 21,357), whether PGS for alcohol use disorders, cannabis use disorders, depression, externalizing, posttraumatic stress disorder, and schizophrenia were associated with subsequent diagnoses via a phenome-wide survival analysis. RESULTS: Multiple SDoHs were associated with lifetime SUD diagnosis, with annual household income having the largest overall associations (e.g. <$10 K annually vs $100 K-$150 K annually: OR = 4.18; 95% CI = 3.92, 4.45). There were 86 phenome-wide significant PGS associations with subsequent diagnoses across various bodily systems. PGSs for alcohol use disorders, posttraumatic stress disorder, and schizophrenia were each associated with time to their respective diagnoses. CONCLUSIONS: Social determinants, especially those related to income, have profound associations with lifetime SUD risk. Additionally, PGSs for psychiatric conditions are associated with multiple post-SUD diagnoses within those with a SUD, suggesting PGS may capture information beyond lifetime risk, including timing and severity of comorbidities related to SUD.
A causal role of the ventromedial prefrontal cortex in regulating anticipated regret and risk behaviors in trait anxiety.
Ai H, Wang M, Zhang M … +6 more , Zeng Y, Gao J, Huang L, Duan L, Xu P, An L
Psychol Med · 2026 Jun · PMID 42219756 · Full text
BACKGROUND: Individuals with high trait anxiety (HA) exhibit maladaptive goal-directed behaviors, which are associated with dysfunctional counterfactual-thinking during decision-making. While lesion studies suggest the c...
BACKGROUND: Individuals with high trait anxiety (HA) exhibit maladaptive goal-directed behaviors, which are associated with dysfunctional counterfactual-thinking during decision-making. While lesion studies suggest the causal role of the ventromedial prefrontal cortex (vmPFC) in counterfactual-thinking, its modulatory role in anxiety-related counterfactual decision-making remains uncharacterized. Here, we bridge this gap by examining the characteristics of decision-making (forward counterfactual) and emotion responses (backward counterfactual) in trait anxiety, as well as its underlying modulatory mechanisms by targeting at the vmPFC. METHODS: A counterfactual-thinking paradigm was employed to identify the patterns of goal-directed choice and emotional responses in trait anxiety in experiment 1. In all, 107 participants with varied levels of trait anxiety were recruited and counterfactual indices were modeled. In experiment 2, the high-definition transcranial direct current stimulation (HD-tDCS) was applied to modulate forward and backward counterfactual responses targeting at the vmPFC in HA. Based on the exploratory results of experiment 1, 61 participants with HA were randomly assigned to cathodal or sham stimulation. RESULTS: High level of anxiety was associated with stronger emotional responses to backward counterfactuals, more anticipations of regret to forward counterfactuals, higher value-expectations to potential rewards, and more risk-taking behaviors. Related to sham, cathodal HD-tDCS over the vmPFC in HA showed normalized sensitivity to anticipated regret, which leads to less risk-taking behaviors during goal-directed decision-making. CONCLUSIONS: The findings provide evidences of disrupted forward and backward counterfactual processing in anxious individuals, wherein the vmPFC plays a modulatory role. Targeting vmPFC with noninvasive stimulation may normalize maladaptive decision patterns in anxiety and anxiety disorders.
Structure and temporal stability of adolescent psychotic experiences: findings from a German longitudinal cohort study.
Nguyen PM, Schäfer B, Kiernan G … +5 more , Berg F, Luhmann M, Kelleher I, Schneider S, Rus-Calafell M
Psychol Med · 2026 Jun · PMID 42219755 · Full text
BACKGROUND: Psychotic-like experiences (PLEs) are common in adolescence and often associated with later mental health difficulties. Although many psychosocial factors are related to PLEs, little is known about how these...
BACKGROUND: Psychotic-like experiences (PLEs) are common in adolescence and often associated with later mental health difficulties. Although many psychosocial factors are related to PLEs, little is known about how these factors interact over time. Longitudinal network analysis allows examination of the stability of symptom associations and identification of potential intervention targets. This study investigated the structure and temporal stability of PLE networks in a large community-based adolescent cohort. METHODS: Adolescents aged 13-19 years (N = 605 with complete data across all time points) completed assessments at baseline, 12 months, and 24 months. Measures included positive and negative PLEs, cognitive biases, depression, anxiety, trauma, and interpersonal sensitivity. Networks were estimated at each time point, and permutation-based tests were used to compare network structure and overall connectivity across time. Centrality stability was assessed using bootstrapping procedures. RESULTS: Network structures were stable across the 2-year period, with no significant differences in overall organization or connectivity between time points. Depression consistently showed the highest centrality, followed by anxiety and attributional bias. Positive PLEs were most strongly associated with anxiety, while negative PLEs showed their strongest associations with depression. Attributional bias remained centrally positioned and was strongly linked to trauma. All networks showed robust accuracy and high stability. CONCLUSIONS: Despite considerable developmental change during adolescence, the psychosocial architecture of PLEs remained notably stable. Depression, anxiety, and attributional biases emerged as consistent key nodes, highlighting them as promising targets for prevention and early intervention in adolescents at risk for persistent PLEs.
Adherence to the EAT-Lancet diet and neuropsychiatric disorders: a systematic review and meta-analysis.
Wang Y, Li Z, Wu Z … +5 more , Hu W, Wu H, Hu Y, Ju Y, Zhang Y
Psychol Med · 2026 Jun · PMID 42219754 · Full text
Neuropsychiatric disorders (NPDs) are a leading cause of disability worldwide. The predominantly plant-based EAT-Lancet diet has been proposed to confer neuropsychiatric benefits, yet evidence remains limited. This study...
Neuropsychiatric disorders (NPDs) are a leading cause of disability worldwide. The predominantly plant-based EAT-Lancet diet has been proposed to confer neuropsychiatric benefits, yet evidence remains limited. This study synthesized associations between adherence to the EAT-Lancet diet and neuropsychiatric outcomes. We searched PubMed, Web of Science, Embase, Scopus, and ProQuest Dissertations and Theses Global through September 4, 2025. Observational studies reporting associations between EAT-Lancet adherence and NPDs were included. Binary outcomes were pooled as hazard ratios (HRs) or odds ratios (ORs), and continuous outcomes as regression coefficients (β). Subgroup, sensitivity, and publication-bias analyses were performed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). Twenty-two cohort and six cross-sectional studies were included. Higher adherence to the EAT-Lancet diet was associated with lower risks of depression (OR 0.76; 95% CI 0.71-0.81), anxiety (OR 0.82; 0.76-0.89), stroke (HR 0.84; 0.76-0.92), and dementia (HR 0.96; 0.93-1.00), whereas no significant association was observed for global cognitive function (β 0.02; -0.01 to 0.06). Sensitivity analyses supported robustness. Certainty of evidence was very low for anxiety, depression, and cognition, and low for stroke and dementia. Greater adherence to the EAT-Lancet diet was associated with lower risks of depression, anxiety, stroke, and dementia. However, given the low certainty of evidence, findings should be interpreted cautiously. Further large prospective studies and randomized controlled trials are warranted to improve evidence quality and clarify the potential role of the EAT-Lancet diet in neuropsychiatric disease prevention.
Childhood paternal abuse and low paternal affection predict adult panic symptoms 18 years later via actigraphy-indexed sleep disruptions.
Zainal NH, Van Doren N
Psychol Med · 2026 Jun · PMID 42219750 · Full text
BACKGROUND: Child abuse and low parental affection are established risk factors for higher adulthood panic disorder (PD) severity, but their plausible sleep mediators are under-investigated. We thus examined how actigrap...
BACKGROUND: Child abuse and low parental affection are established risk factors for higher adulthood panic disorder (PD) severity, but their plausible sleep mediators are under-investigated. We thus examined how actigraphy indices mediated the links between child parental abuse and affection deficits to adulthood PD severity. METHODS: Community-dwelling adult participants ( = 1,054) completed a series of self-reports on child parental abuse and affection at Wave 1. An eight-day actigraphy protocol was conducted at Wave 2, 9 years later. Telephone-administered clinical interviews assessing PD symptoms were conducted in W1 and Wave 3, separated by 18 years. A series of bias-corrected, bootstrapped causal mediation analyses was performed. RESULTS: Paternal, but not maternal abuse, predicted higher rest- and sleep-stage actigraphy markers after 9 years (βs = 0.263-469.79, < .001), comprising more activity counts, longer wake time, higher wake time percentage, and wake bouts. These markers, thereby, mediated the trajectory from paternal abuse to higher PD severity (average causal mediation effects (ACMEs): βs = 0.003-0.020, 95% CIs excluding zero, < .001). Likewise, paternal affection deficits predicted greater disturbances in rest- and sleep-stage actigraphy (all < .05), thereby mediating the link to greater PD severity (ACMEs: βs = 0.001-0.002, ≤ .04). Neither maternal abuse nor affection was a significant mediator. DISCUSSION: These outcomes aligned with, but do not verify, a causal mediation argument wherein actigraphy-derived nocturnal sleep-wake disturbances partially accounted for the trajectory from adverse paternal caregiving encounters to adulthood PD severity. Strategically targeting sleep disturbances may reflect a viable intervention approach for persons with past child paternal abuse learning histories.
Childhood trauma as a mediator between autistic traits and depression: Evidence from the ALSPAC birth cohort.
Underwood JFG, Madley-Dowd P, Dardani C … +5 more , Hull L, Kwong ASF, Pearson RM, Hall J, Rai D
Psychol Med · 2026 May · PMID 42212598 · Full text
BACKGROUND: Autistic traits have been associated with greater risk of childhood trauma and adulthood psychopathology. However, the role that childhood trauma plays in the association among autism, autistic traits, and de...
BACKGROUND: Autistic traits have been associated with greater risk of childhood trauma and adulthood psychopathology. However, the role that childhood trauma plays in the association among autism, autistic traits, and depression in adulthood is poorly understood. METHODS: We used a UK-based birth cohort with genotype and phenotype data on autism, autistic traits, childhood trauma, and depression in up to 9,659 individuals prospectively followed up until age 28 years. Using mixed-effects growth-curve models, we assessed trajectories of depression symptoms over time according to autism diagnosis, autism polygenic score and trait measures, and explored whether these differed by trauma exposure. We further investigated the association between autism/autistic traits and depression in adulthood using confounder-adjusted logistic regression models and undertook mediation analyses to investigate the relationship with childhood trauma. RESULTS: All autism variables demonstrated increased depressive symptom trajectories between ages 10 and 28 years. Social communication difficulties (SCDs) were most strongly associated with a depression diagnosis in adulthood (age 24 OR = 1.86; 95% CIs: 1.15-3.01). Trauma and autistic traits combined to further increase depression symptom scores. Mediation analyses provided evidence for direct pathways between autistic traits and increased risk of depression alongside indirect pathways through increased risk of trauma. CONCLUSIONS: Autism/autistic traits increase the odds of experiencing childhood trauma and of being diagnosed with depression at ages 18 and 24. Depressive symptom trajectories emergent in childhood persist into adulthood. The combined effect of SCDs and childhood trauma is greater than the individual exposures, suggesting worse depression symptomatology following trauma in individuals with SCDs.
Evaluating psychosis-specific effects of trauma exposure in early-onset and adult-onset psychosis.
Unzueta J, Mathias S, Lanzagorta N … +15 more , Mollon J, Knowles EEM, Deaso E, Cadavid L, Brownstein C, D'Angelo E, Gonzalez-Heydrich J, Ramírez P, Sarmiento E, Bustamante C, Almasy L, Nicolini H, Pearlson G, Glahn DC, Rodrigue A
Psychol Med · 2026 May · PMID 42212570 · Full text
Trauma is a risk factor for early-onset (EOP) and adult-onset (AOP) psychosis and is also associated with other psychiatric diagnoses and poorer fputcomes in the general population. We examined (1) whether trauma effects...
Trauma is a risk factor for early-onset (EOP) and adult-onset (AOP) psychosis and is also associated with other psychiatric diagnoses and poorer fputcomes in the general population. We examined (1) whether trauma effects are specific to psychosis and (2) whether these effects differ between EOP and AOP.Linear regression models evaluated trauma exposure in two samples (EOP: 647 cases, 694 controls; AOP: 162 cases, 230 controls) as a function of psychotic and nonpsychotic psychiatric diagnosis (NPD) status. Parallel models assessed associations between trauma and symptom severity, global functioning, and cognition. Relative to individuals without psychiatric disorders, participants with psychosis and comorbid NPDs reported the greatest trauma exposure (EOP: β = 0.95; AOP: β = 1.1), followed by those with psychosis only (EOP: β = 0.67; AOP: β = 0.41) and NPDs only (EOP: β = 0.47; AOP: β = 0.36). Greater numbers of NPDs were associated with higher trauma exposure regardless of psychosis status (EOP: β = 0.15; AOP: β = 0.24). Trauma was associated with greater symptom severity (EOP: β = 0.13; AOP: β = 0.14) and poorer global functioning (EOP: β = -0.21; AOP: β = -0.13), but not cognition. No psychosis-by-trauma interactions were observed.Psychosis-specific effects were limited to greater trauma exposure, while trauma-related impacts on outcomes were similar across diagnostic groups. Findings were consistent across EOP and AOP. Results highlight the need for trauma-informed care in psychiatry given broad effects that influence disease course and prognosis.
Factors associated with social functioning by relapse frequency in Japanese outpatients with schizophrenia: the Multicenter Treatment Survey and Assessments for Schizophrenia in Psychiatric Clinics (MUSASI).
Takekita Y, Katsumoto E, Adachi N … +14 more , Kubota Y, Edagawa K, Azekawa T, Ueda H, Tamura T, Hongo S, Goto E, Hida H, Miki K, Fujii C, Watanabe K, Kato M, Yasui-Furukori N, Takeuchi H
Psychol Med · 2026 May · PMID 42208959 · Full text
BACKGROUND: Impaired social functioning substantially affects the quality of life of patients with schizophrenia; however, it remains unclear whether the factors associated with social functioning differ according to rel...
BACKGROUND: Impaired social functioning substantially affects the quality of life of patients with schizophrenia; however, it remains unclear whether the factors associated with social functioning differ according to relapse frequency. This study aimed to examine the differences in these factors among Japanese outpatients with schizophrenia, stratified by relapse frequency. METHODS: This nationwide cross-sectional study, the Multicenter Treatment Survey and Assessments for Schizophrenia in Psychiatric Clinics (MUSASI), was conducted in 330 psychiatric clinics in Japan between September and October 2023. A total of 10,081 patients diagnosed with schizophrenia-related disorders were analyzed. Patients were categorized as nonrelapsers, low-frequency relapsers (1-2 relapses), or high-frequency relapsers (≥3 relapses). Social functioning was assessed using the Social and Occupational Functioning Assessment Scale, with scores ≥61 defined as high functioning. RESULTS: This study included 3,670 nonrelapsers, 4,428 low-frequency relapsers, and 1,983 high-frequency relapsers. Overall, 55.8% ( = 5,631) of patients were classified as having high social functioning. Across all groups, employment, shorter periods of instability during the past year, lower Clinical Global Impression-Severity scores, and fewer negative symptoms were significantly associated with higher social functioning. Group-specific associations were also observed: in nonrelapsers and low-frequency relapsers, positive symptoms and medication-related factors were relevant, whereas in low- and high-frequency relapsers, marital history was associated, and in high-frequency relapsers, the absence of tardive dyskinesia emerged as a factor. CONCLUSIONS: Factors associated with social functioning differed according to relapse frequency, highlighting the need for relapse frequency-based, stratified intervention strategies.
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