Psychological Medicine[JOURNAL]
Sun
200 papers
Integrative multi-omics identifies as a novel pharmacological target for bipolar disorder.
Yuan C, Zhang B, Liang Y … +9 more , Ran J, Hu S, Liu A, Liu Y, Qin F, Jian L, He Y, Han F, Zhang C
Psychol Med · 2026 May · PMID 42206661 · Full text
BACKGROUND: Current bipolar disorder (BD) therapies suffer from limited efficacy and adverse effects, necessitating mechanistically grounded targets. METHODS: We integrated BD genome-wide association study data (158,036...
BACKGROUND: Current bipolar disorder (BD) therapies suffer from limited efficacy and adverse effects, necessitating mechanistically grounded targets. METHODS: We integrated BD genome-wide association study data (158,036 cases; 2,796,499 controls) with brain proteomics (ROSMAP and Banner dorsolateral prefrontal cortex, = 376 and 152) to perform proteome-wide association studies (PWAS). Bayesian colocalization and summary-data-based Mendelian randomization (SMR) prioritized causal genes. Cell-type-specific transcriptomics validated dysregulation in iPSC-derived neurons, astrocytes, and postmortem hippocampus/prefrontal cortex. Weighted gene co-expression networks (WGCNAs), functional enrichment, and molecular docking assessed functional pathways and druggability. RESULTS: PWAS identified eight BD-associated genes (false discovery rate < 0.05), with emerging as the top candidate. Colocalization ( > 0.8) and SMR supported a causal association of with BD, with no pleiotropy (heterogeneity in dependent instruments > 0.01); expression decreased in BD across neurons ( = 4.26 × 10), astrocytes ( = 2.09 × 10), hippocampus ( = 9.80 × 10, = -2.738), and prefrontal cortex ( = 1.44 × 10, = -2.580); WGCNA positioned as a key regulator (module membership/gene significance < 0.05) of co-expression networks enriched for BD-associated processes including neurotransmitter secretion and postsynaptic actin cytoskeleton organization ( < 0.05); molecular docking revealed favorable-affinity binding (ΔG < -4 kcal/mol) between DOC2A and BD-related drugs and neuroprotective compounds. CONCLUSIONS: Our convergent multi-omics framework highlights dysregulation as a key contributor to synaptic dysfunction in BD and nominates it as a promising therapeutic target. The demonstrated interaction with existing neuroactive compounds provides immediate translational avenues.
Affective dynamics in adolescents with major depressive disorder and subthreshold depression: an experience sampling study.
Liu TCY, Kwok NT, Chan SS … +10 more , Mo FYM, Ching EWK, Chau SWH, Wong OWH, Ma SL, Tsoi KKF, Lai KYC, Leung PWL, Hung SF, So SH
Psychol Med · 2026 May · PMID 42206400 · Full text
BACKGROUND: Sub-threshold depression (SD) affects around 11% of adolescents and can be as impairing as conditions reaching the full diagnostic criteria of Major Depressive Disorder (MDD). However, limited research has be...
BACKGROUND: Sub-threshold depression (SD) affects around 11% of adolescents and can be as impairing as conditions reaching the full diagnostic criteria of Major Depressive Disorder (MDD). However, limited research has been conducted on how affective disturbances manifest in SD during adolescence, a period of affective vulnerability. We compared three groups of adolescents along the spectrum of depression on their positive affective (PA) and negative affective (NA) levels and dynamics, including variability, inertia, and reactivity to event-related stress and pleasure in daily life. METHOD: One hundred and ninety eight adolescents (age 12-18), grouped by psychiatric diagnosis (MDD = 66; SD = 35; healthy controls, HC = 88), completed a 14-day experience sampling on their smartphone, clinical ratings, and questionnaires. They were recruited from multiple sources, including an epidemiologic study and specialist clinics. RESULTS: The level of NA was the highest in MDD, followed by SD and HC; vice versa for PA. MDD and SD displayed greater NA variability than HC. NA inertia was greater in MDD than SD and HC. NA reactivity (to event-related pleasure and stress) and PA reactivity (to event-related pleasure) were greater in MDD and SD than HC. SD showed greater PA reactivity to event-related stress than MDD. CONCLUSIONS: Adolescents with SD were as reactive and expansive in their NA experience as the MDD group, but they did not stay in that negative state for as long. The SD group was more reactive than HC to event-related pleasure and stress, suggesting heightened sensitivity. Clinical implications of emotional sensitivity and flexibility on early intervention for depression are discussed.
Positive and negative maternal mental health demonstrate distinct pathways to childhood depression.
Huang P, Manahan AMA, Lee MYH … +14 more , Chan SY, Ngoh ZM, Kee MZL, Phua DY, Sathyapalan AS, Chong YS, Gluckman PD, Chen H, Fortier MV, Daniel LM, Zhou JH, Law EC, Meaney MJ, Tan AP
Psychol Med · 2026 May · PMID 42206398 · Full text
BACKGROUND: Maternal mental health strongly influences child development and depression risk. This study investigated how positive and negative dimensions of prenatal maternal mental health differentially shape childhood...
BACKGROUND: Maternal mental health strongly influences child development and depression risk. This study investigated how positive and negative dimensions of prenatal maternal mental health differentially shape childhood depressive symptoms through cognitive mediators. METHODS: Participants were drawn from the (GUSTO) cohort. Of the 1198 mother-child dyads enrolled, 523 (52.6% boys) had sufficient data for the mediation analysis. Maternal mental health at 26 weeks' gestation was assessed using a bifactor model derived from the Beck Depression Inventory-II, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale. Child language ability was measured at age 2 years with the Bayley Scales of Infant Development, executive function at age 7 years with the Behaviour Rating Inventory of Executive Function, and depressive symptoms at age 9 years with the Children's Depression Inventory-2. Serial mediation models tested hypothesized pathways. RESULTS: Distinct mediation pathways emerged. Positive maternal mental health was associated with enhanced early language ability, which in turn was associated with fewer depressive symptoms in later childhood ( = -0.017, 95% CI: -0.042, -0.003). Conversely, negative maternal mental health was associated with poorer executive functioning, which in turn was associated with more depressive symptoms ( = 0.040, 95% CI: 0.016-0.077). CONCLUSIONS: Positive and negative maternal mental health are linked to childhood depressive symptoms through distinct neurocognitive pathways. By identifying language and executive function as specific developmental mediators, our findings point to targeted and developmentally sensitive intervention opportunities to disrupt intergenerational pathways of depression.
Effectiveness of 13-week dialectical behavior therapy skills training for non-suicidal self-injury: a multi-center randomized clinical trial in China.
Ni F, Wu S, Liang M … +18 more , Liu C, Zhang P, Zhang D, Rodriguez M, Glasenapp J, Yin C, Long J, Liu Y, Sun Y, Wu X, Liu G, Jiang X, Wang X, Lv H, Zhang Z, Wang S, Rosenthal Z, Wang C
Psychol Med · 2026 May · PMID 42206397 · Full text
BACKGROUND: Dialectical behavior therapy skills training (DBT-ST) has received empirical evidence for treating non-suicidal self-injury (NSSI). However, its effectiveness in Chinese contexts remains understudied. This st...
BACKGROUND: Dialectical behavior therapy skills training (DBT-ST) has received empirical evidence for treating non-suicidal self-injury (NSSI). However, its effectiveness in Chinese contexts remains understudied. This study aims to explore the effectiveness of DBT-ST for NSSI in a clinical sample of individuals with NSSI. METHODS: We conducted a multicenter, randomized clinical trial in China to evaluate the effectiveness of a 13-week DBT-ST compared with social support group therapy (SSGT). A total of 196 individuals with mental disorders and NSSI were recruited. The primary outcome was the frequency of NSSI thoughts and behaviors, assessed using the Ottawa Self-Injury Inventory. RESULTS: Participants were randomized to the DBT-ST group ( = 97) or the SSGT group ( = 99). DBT-ST was significantly more effective than SSGT in reducing the frequency of NSSI behaviors. It also showed superior effects on borderline symptoms and multiple domains of psychological functioning, including emotion dysregulation, impulsivity, alexithymia, mindfulness, psychological resilience, and emotional intelligence. Both groups exhibited significant reductions in the frequency of NSSI thoughts, suicidal ideation and attempts, and depression, with no significant between-group differences in these outcomes. CONCLUSIONS: These findings confirm that the 13-week DBT-ST intervention is an effective treatment for Chinese patients with NSSI in clinical settings.
Familial coaggregation and shared genetic loading of mental disorders and cardiovascular diseases.
Chen PC, Pan YJ, Lin MC … +4 more , Su MH, Fan CC, Wu CS, Wang SH
Psychol Med · 2026 May · PMID 42206393 · Full text
BACKGROUND: The high comorbidity between mental and cardiovascular diseases is widely recognized, but the underlying mechanisms are not yet well understood. We investigated the familial coaggregation and shared genetic l...
BACKGROUND: The high comorbidity between mental and cardiovascular diseases is widely recognized, but the underlying mechanisms are not yet well understood. We investigated the familial coaggregation and shared genetic loading between these diseases. METHODS: Using claims data from Taiwan's universal health insurance program, we identified cohorts of 4,513,509 individuals with parental information and 3,330,181 with full-sibling information born between 1970 and 1999, and followed up until 2020. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. Multiple logistic regression models were used to estimate the association of parental history, full-sibling history, and polygenic risk scores (PRSs) for severe mental illnesses (schizophrenia, bipolar disorder, major depressive disorder [MDD]) with the risk of myocardial infarction, stroke, peripheral arterial disease (PAD), and heart failure. RESULTS: Individuals with a parental history of schizophrenia, bipolar disorder, or MDD were more likely to have stroke and PAD. Coaggregation in full-siblings was observed for MDD with myocardial infarction and heart failure, bipolar disorders with stroke, and schizophrenia with PAD. The PAD risk increased with more relatives affected by MDD; the magnitude of association was larger when both parents were affected than when either parent was affected, and when there were two affected siblings than in those with only one. MDD PRS was positively associated with the risk of myocardial infarction and PAD. CONCLUSIONS: This study revealed familial coaggregation between mental and cardiovascular diseases, and shared polygenic liability of MDD with cardiovascular diseases. Our findings suggest the potential benefit of family-based integrated screening and preventive strategies.
Predicting functional remission after antipsychotic discontinuation: a real-world study in schizophrenia.
Lu C, Dong Y, Zhai Z … +12 more , Gao T, Luo M, Chang D, Chen J, Xue J, Zhao Y, Xiang Q, Li X, Ma X, Wei Z, Feng T, Liu D
Psychol Med · 2026 May · PMID 42206392 · Full text
BACKGROUND: This real-world study aimed to characterize patients with schizophrenia who achieve sustained good functional outcomes after antipsychotic discontinuation and to develop the Functional Remission in Schizophre...
BACKGROUND: This real-world study aimed to characterize patients with schizophrenia who achieve sustained good functional outcomes after antipsychotic discontinuation and to develop the Functional Remission in Schizophrenia after Antipsychotic Discontinuation (FURSAD) predictive model. METHODS: We retrospectively identified individuals aged 18-65 years with schizophrenia (ICD-10) from the Shanghai Mental Health Center discharge database. Patients who discontinued antipsychotics for ≥1 year were classified as functional remission (FR) or functional non-remission (FNR) based on functioning assessments. Sociodemographic, clinical, and treatment-related data were extracted blindly from hospital records and structured interviews. RESULTS: Among 4,166 discharged patients screened, 180 met the inclusion criteria (FR: 116; FNR: 64). Six independent predictors were identified: total disease course, Clinical Global Impression-Severity (CGI-S) score, Positive and Negative Syndrome Scale (PANSS) emotional distress subscale score, use of first-generation antipsychotics, discontinuation due to treatment benefits, and discontinuation due to lack of insight. The logistic regression model showed strong predictive performance (AUC = 0.867, 95% CI 0.813-0.921), with 82.8% sensitivity and 81.9% specificity. Internal validation was performed via 10-fold cross-validation. CONCLUSION: Discontinuation motives and illness trajectory are relevant in predicting long-term functional outcomes. A limitation is that a substantial number of patients could not be recontacted or declined participation, which may introduce selection bias. The FURSAD nomogram may help clinicians estimate the probability of FR 4.5 years post-antipsychotic discontinuation in patients previously on antipsychotics for ≥3 years.
Patterns of subjective well-being and psychopathology trajectories in adolescence: a population-based cohort study.
Uno A, Nagaoka D, Minami R … +10 more , Tanaka R, Sawai Y, Okuma A, Tomoshige N, Yamaguchi S, Yamasaki S, Miyashita M, Nishida A, Ando S, Kasai K
Psychol Med · 2026 May · PMID 42178148 · Full text
BACKGROUND: Mental health encompasses subjective well-being (SWB) as well as psychopathology (PP). SWB and PP are related but separate domains: some individuals experience high SWB despite high PP, and others experience...
BACKGROUND: Mental health encompasses subjective well-being (SWB) as well as psychopathology (PP). SWB and PP are related but separate domains: some individuals experience high SWB despite high PP, and others experience low SWB despite minimal PP. Given substantial and heterogeneous developmental changes in both domains during adolescence, examining their co-developmental trajectories may clarify how they integrate across this period. METHODS: Using data from the Tokyo Teen Cohort ( = 2994), a population-based prospective birth cohort study, we conducted parallel process latent class growth analysis to cluster SWB-PP trajectories at ages 10, 12, 14, and 16 years. We then investigated various sociodemographic, individual, familial, and socioenvironmental correlates for each class. RESULTS: We identified four distinct classes: high SWB-low PP (55.0%), high SWB-mid PP (20.2%), low SWB-mid PP (17.0%), and mid SWB-high PP (7.7%). SWB declined from ages 10 to 16 years across all four classes. Lower PP did not necessarily correspond to higher SWB, and in some pairs of classes, the relationship between SWB and PP levels was reversed. When comparing the two classes with moderate PP, higher aspirations, more prosocial behavior, and better interpersonal relationships were associated with the high SWB class. In contrast, being female and having a higher household income were associated with the low SWB class. CONCLUSIONS: Discrepant SWB-PP trajectories suggest characteristic patterns of developmental integration between these domains during adolescence. Considering their interplay may complement domain-specific approaches and inform psychosocial supports aimed at maintaining SWB even in the presence of PP.
Global prevalence of prolonged grief disorder during the COVID-19 pandemic under standardized diagnostic frameworks: A systematic review and meta-analysis.
Li S, Qiu L, Li Y … +4 more , Liu X, Luo Z, Liu J, Ma X
Psychol Med · 2026 May · PMID 42165098 · Full text
Prolonged grief disorder (PGD), recently classified in ICD-11 and DSM-5-TR, is characterized by persistent and functionally impairing grief lasting beyond 6-12 months. The COVID-19 pandemic was accompanied by widespread...
Prolonged grief disorder (PGD), recently classified in ICD-11 and DSM-5-TR, is characterized by persistent and functionally impairing grief lasting beyond 6-12 months. The COVID-19 pandemic was accompanied by widespread mortality, social isolation, disrupted mourning rituals, and social disconnection, raising concerns about a potentially high burden of PGD during the pandemic period. We conducted a systematic review and meta-analysis, following PRISMA guidelines and PROSPERO registration (CRD42023463720), to estimate PGD prevalence under standardized ICD-11 and DSM-5-TR diagnostic frameworks and to examine potential moderators during the COVID-19 pandemic. PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2024. Eligible studies included adults who experienced bereavement during the pandemic and were assessed using validated PGD instruments (PG-13-R, ICG, BGQ). Random-effects models were applied to pool prevalence estimates, with subgroup and meta-regression analyses. Thirteen studies comprising 5,766 participants were included. The pooled prevalence of PGD during the pandemic period was 24% (95% CI: 13%-36%), with the highest estimates observed in China (43%, 95% CI: 33%-54%). In the overall pooled analysis, studies applying DSM-5-TR criteria yielded lower prevalence estimates than those using ICD-11 criteria (18% vs.26%, = 0.41). Digital interventions showed no statistically significant pooled effects (Hedges' = -0.38, 95% CI: -0.90 to 0.14). The high and geographically heterogeneous prevalence of PGD observed during the COVID-19 pandemic underscores the need to strengthen mental health surveillance, standardized assessment, and service accessibility in large-scale public health emergencies, and provides important evidence to inform population-level interventions and resource allocation strategies.
Altered amygdala resting-state functional connectivity in anxiety disorders: a coordinate-based meta-analysis.
Lu L, Xu H, Wang R … +6 more , Zhang B, Wu B, Zhang L, Li X, Gong Q, Strawn JR
Psychol Med · 2026 May · PMID 42165096 · Full text
BACKGROUND: Anxiety disorders are associated with disrupted amygdala connectivity; however, resting-state functional MRI studies have reported heterogeneous findings. To clarify these inconsistencies, we conducted a meta...
BACKGROUND: Anxiety disorders are associated with disrupted amygdala connectivity; however, resting-state functional MRI studies have reported heterogeneous findings. To clarify these inconsistencies, we conducted a meta-analysis of amygdala-based connectivity studies. METHODS: A systematic search of Embase, PubMed, and Web of Science was performed through December 26, 2025. Studies comparing amygdala-based whole-brain resting-state functional connectivity in patients with anxiety disorders versus healthy controls were included. Meta-analysis was conducted with the latest software - Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), which employs voxel-wise tests and multiple corrections to minimize false positives. Subgroup analyses were performed to examine differences by age and hemisphere. RESULTS: Fifteen datasets (378 patients, 405 controls) were included. Compared to healthy controls, patients with anxiety disorders had decreased amygdala-anterior cingulate cortex (ACC, = -0.54, 95% confidence interval [CI]: -0.73 to -0.35) connectivity and increased connectivity with the left superior temporal gyrus ( = 0.46, 95% CI: 0.27-0.65), middle temporal gyrus ( = 0.38, 95% CI: 0.19-0.57), and cuneus ( = 0.35, 95% CI: 0.17-0.53). After threshold-free cluster enhancement correction, only reduced amygdala-ACC connectivity remained significant ( = -0.54, 95% CI: -0.73 to -0.35). Subgroup analyses confirmed this effect was driven mainly by adult patients and the left amygdala. CONCLUSIONS: Reduced connectivity between the left amygdala and the ipsilateral ACC was the most robust neuroimaging marker of anxiety disorders, which suggests a lateralized vulnerability. By applying updated analytic methods, this study refines our understanding of the neuropathology of anxiety disorders and provides a potential primary target for biomarker development and novel interventions.
Altered social and cognitive control interactions during decision-making in social anxiety.
Li Y, Van Dam NT, Wang Z … +2 more , Luo Y, Xu P
Psychol Med · 2026 May · PMID 42145274 · Full text
BACKGROUND: Social anxiety is characterized by fear and avoidance of social situations, yet many everyday decisions are made in the presence of others and are shaped by social influence. However, the influences of social...
BACKGROUND: Social anxiety is characterized by fear and avoidance of social situations, yet many everyday decisions are made in the presence of others and are shaped by social influence. However, the influences of social anxiety on social decision-making and the underlying neural processes are not well understood. METHODS: Fifty-five adults with varying levels of social anxiety completed a social risk decision-making task during functional magnetic resonance imaging (fMRI). In each trial, participants chose between a safe option and a risky gamble against either a human or a computer opponent, with or without information about others' choices. Social influence on choice was quantified using repeated-measures analyses and drift-diffusion modeling, while brain activity and functional connectivity were examined using whole-brain analyses. RESULTS: Compared to individuals with lower social anxiety, those with higher social anxiety showed reduced conformity to others' risky choices, specifically when interacting with human, but not computer, opponents, together with a stronger starting-point bias toward safe options. These behavioral differences were accompanied by lower dorsolateral prefrontal cortex (dlPFC) activation and stronger dlPFC-temporoparietal junction (TPJ) functional connectivity. CONCLUSIONS: Social anxiety is associated with decreased social approach and reduced social influence from others in social decision contexts. Decreased activation of the prefrontal control system and its increased interactions with the social brain network point toward a conflict between heightened social monitoring and inefficient executive control. By distinguishing social-context effects from general risk aversion, this study provides a refined mechanistic framework for understanding how impaired regulatory control shapes maladaptive social decision-making in social anxiety.
Delusional disorder and its differentiation from schizophrenia: A narrative review.
Rossi Grauenfels D, Henriksen MG, Nordgaard J
Psychol Med · 2026 May · PMID 42138058 · Full text
The nosological status and psychopathology of delusional disorder have been a subject of debate since Kraepelin distinguished it from schizophrenia and affective psychoses. Contemporary diagnostic manuals define delusion...
The nosological status and psychopathology of delusional disorder have been a subject of debate since Kraepelin distinguished it from schizophrenia and affective psychoses. Contemporary diagnostic manuals define delusional disorder primarily by the presence of delusions, offering limited guidance for its differentiation from schizophrenia. Notably, DSM-5 introduced a major, seemingly unexplained change by allowing bizarre delusions in delusional disorder, contrary to ICD-11, prior DSM editions, and classical descriptions. This narrative review revisits the seminal works of six classical authors (Kraepelin, Jaspers, Kretschmer, Sérieux and Capgras, and De Clérambault), who shaped the concept of delusional disorder (paranoia), and their detailed clinical cases of the disorder. All considered delusional disorder to be an independent psychotic disorder, characterized by chronic, systematized, nonbizarre delusions, preservation of personality, and minimal hallucinations, with a largely intact experiential framework outside of the delusional theme. Additional features such as delusional misinterpretations, illusions, and false memories were also emphasized in the classical literature. We examined these authors' clinical cases of delusional disorder for the presence of delusional features characteristic of schizophrenia (delusional mood, first-rank symptoms, autistic-solipsistic delusions, and double bookkeeping), which index alterations in the structure of experience rather than mere delusional content. Such delusions were rarely found in the classical clinical cases of delusional disorder. Our findings highlight psychopathological distinctions between delusional disorder and schizophrenia, suggesting that schizophrenia involves a qualitative alteration of the experiential framework that is absent in delusional disorder. These findings raise concerns about the validity of the DSM-5 change, allowing bizarre delusions in delusional disorder.
Effectiveness of a one-year smoking cessation intervention for people with severe mental illness: results of the KISMET cluster-randomized controlled trial.
Küçükaksu M, Hoekstra T, Vermeulen JM … +4 more , Jansen L, Helmig S, van Meijel B, Adriaanse MC
Psychol Med · 2026 May · PMID 42138038 · Full text
BACKGROUND: This study evaluated the effectiveness of a one-year smoking cessation intervention for people with severe mental illness compared with treatment as usual (TAU) in outpatient mental healthcare. METHODS: The K...
BACKGROUND: This study evaluated the effectiveness of a one-year smoking cessation intervention for people with severe mental illness compared with treatment as usual (TAU) in outpatient mental healthcare. METHODS: The KISMET study is a pragmatic cluster-randomized controlled trial conducted in 21 outpatient mental healthcare teams in the Netherlands. Eleven teams delivered the KISMET intervention comprising cognitive-behavioral and peer support, combined with optional pharmacological reatment. Ten teams participated in the TAU condition. We collected data between October 2022 and July 2024. The primary outcome was self-reported smoking cessation at 12 months, verified through exhaled carbon monoxide levels below 10 parts per million. Secondary outcomes included depression and anxiety (HADS), severity of psychotic symptoms (PANSS-6), quality of life (SF-12), disease self-management (PAM-13), lipid profile, blood pressure, body mass index, glucose level, and physical fitness. Crude and adjusted linear and multivariable logistic regression and mixed model analyses were performed. RESULTS: Eighty-nine participants were included in the KISMET intervention and 44 in TAU. Smoking cessation rates were significantly higher in the KISMET group at 3 months (OR 12.1, 95% CI 1.4 to 103.7) and at 12 months (OR 4.2, 95% CI 1.0 to 17.2) but not at 6 months (OR 1.9, 95% CI 0.5 to 6.9). No significant differences between groups were found for secondary outcomes. Dropout rates were 58% in the intervention and 32% in the TAU group. CONCLUSIONS: The KISMET intervention shows potential without signs of physical or psychopathological complications. However, results must be interpreted with the high dropout rates in mind.
The emotion dysregulation inventory - self-report: development and psychometric evaluation.
Conner CM, Yu L, Zeglen KN … +2 more , Pilkonis PA, Mazefsky CA
Psychol Med · 2026 May · PMID 42138030 · Full text
BACKGROUND: Emotion dysregulation is a transdiagnostic construct associated with multiple mental health conditions and shown to be an amenable target for treatment. The original Emotion Dysregulation Inventory (EDI) was...
BACKGROUND: Emotion dysregulation is a transdiagnostic construct associated with multiple mental health conditions and shown to be an amenable target for treatment. The original Emotion Dysregulation Inventory (EDI) was created as a proxy-report measure validated in autistic and nonautistic youth. The goal of the current study was to develop a self-report version, the EDI-Self-Report (EDI-SR), that captures a first-person perspective and creates the option of multi-reporter measurement from adolescence through adulthood. METHODS: Using methods developed by the Patient-Reported Outcomes Measurement Information System (PROMIS), potential items and response options were written and tested in cognitive interviews. Two samples (996 participants who are autistic or have other intellectual and developmental disabilities and 1,000 participants selected to be representative of the US census as a nonclinical comparison group) completed the initial item pool. Items were assessed using exploratory and confirmatory factor analyses, item response theory analyses, concurrent calibrations, convergent correlations with comparable legacy measures, internal consistency reliability, and test-retest reliability. RESULTS: Exploratory factor analyses suggested splitting Reactivity and Dysphoria items for confirmatory factor analyses and subsequent analyses. Following analyses, a 25-item Reactivity scale, a 7-item Dysphoria scale, and a 6-item Reactivity short-form scale were finalized. EDI-SR subscales showed convergent validity and superior total information when compared with similar measures, strong internal consistency reliability, and good test-retest reliability. CONCLUSIONS: The EDI-SR provides an efficient, precise measure of ED in autistic individuals, individuals with other intellectual and developmental disabilities, and a US census-matched representative sample, and allows for multi-reporter assessment in clinical and research contexts.
Symptom severity, neighborhood crime, and neural correlates of reappraisal in patients with major depression and social anxiety.
Feurer C, Jimmy J, Uribe M … +5 more , Burkhouse KL, Shankman SA, Phan KL, Ajilore O, Klumpp H
Psychol Med · 2026 May · PMID 42138028 · Full text
BACKGROUND: Cognitive reappraisal deficits are a transdiagnostic risk factor for major depressive disorder (MDD) and social anxiety disorder (SAD) and are observed in patients with these disorders at the neural level. Pr...
BACKGROUND: Cognitive reappraisal deficits are a transdiagnostic risk factor for major depressive disorder (MDD) and social anxiety disorder (SAD) and are observed in patients with these disorders at the neural level. Preliminary research suggests less activation of prefrontal regions during reappraisal (vs. viewing) of negative stimuli associates with overall symptom severity in patients with MDD or SAD, however, this is not reliably observed across studies. Consistent with research showing that reappraisal may only be adaptive when employed to cope with uncontrollable adversity, this study sought to examine whether neighborhood-level adversity (i.e. socioeconomic disadvantage, crime) moderated the relation between internalizing symptom severity and neural correlates of reappraisal. METHODS: This study included patients with a current diagnosis of MDD ( = 51) or SAD ( = 39). Patients completed measures of symptom severity as well as an emotion regulation task while in the scanner to assess neural activation during reappraisal. Patients' addresses were geocoded to assess neighborhood socioeconomic disadvantage and crime. RESULTS: Results indicated that greater symptom severity was associated with decreased activation of key prefrontal regions underlying reappraisal, but only for patients living in neighborhoods characterized by high levels of personal (i.e. violent) crime. Unexpectedly, the opposite was found for patients living in low-crime neighborhoods, such that greater symptom severity was associated with increased neural activation during reappraisal (vs. viewing) of negative stimuli. CONCLUSIONS: Findings highlight the critical importance of considering patients' neighborhood contexts when evaluating associations between symptom severity and neural correlates of reappraisal in patients with internalizing disorders.
A meta-analysis of preventive psychosocial interventions against depressive and anxiety symptoms in older adults.
Saldivia S, Aslan J, Castillo-Carreño A … +2 more , Petkari E, Pietschnig J
Psychol Med · 2026 May · PMID 42132005 · Full text
Common mental disorders (CMDs) such as depression and anxiety are highly prevalent among older adults. While psychosocial interventions are increasingly recognized for their preventive potential, a comprehensive synthesi...
Common mental disorders (CMDs) such as depression and anxiety are highly prevalent among older adults. While psychosocial interventions are increasingly recognized for their preventive potential, a comprehensive synthesis of their effectiveness with nonclinical elderly populations is pending. This study aimed to evaluate the effectiveness of such interventions in reducing depressive and anxiety symptoms among older adults with subclinical symptom levels and to examine potential moderators (that is, intervention type, length, delivery modality, and control group characteristics). A meta-analysis was conducted of 58 randomized controlled trials (RCTs) testing psychosocial interventions aimed at preventing depression and/or anxiety, using validated measures and targeting adults aged ≥60. Moderator variable effects were assessed through mixed-effects meta-regressions, and effect generality was examined using multiverse analyses. Psychosocial interventions showed a moderate postintervention effect in reducing depressive symptoms ( = -0.474) that remained nontrivial and modest at follow-up ( = -0.386) compared to control. For anxiety, a small-to-moderate effect was observed postintervention ( = -0.333), with a small, albeit nominally nonsignificant, effect at follow-up ( = -0.205) compared to control. No significant differences were found between intervention types or control conditions. Younger participants experienced greater reductions in depressive symptoms from pre-to-post-intervention and at follow-up, and in anxiety symptoms from pre-to-post-intervention only. Multiverse analyses showed that intervention effects generalized across numerous variables, thus indicating a remarkable robustness of the findings. Our findings demonstrate that it is important to implement psychosocial interventions in community settings, regardless of intervention type, to protect the elderly against CMDs.
The link between basic visual processing and higher-level social cognition: Eye gaze perception as a bridge in a transdiagnostic sample enriched with social dysfunction.
Mathis K, Blain SD, Locarno L … +7 more , Lasagna CA, DeStefani S, Kraft J, Colombi C, Thakkar KN, Burton CZ, Tso IF
Psychol Med · 2026 May · PMID 42132002 · Full text
BACKGROUND: Social cognitive deficits are common across many psychiatric conditions and contribute to broader social dysfunction. One hypothesized mechanism involves altered basic visual processing, which may disrupt the...
BACKGROUND: Social cognitive deficits are common across many psychiatric conditions and contribute to broader social dysfunction. One hypothesized mechanism involves altered basic visual processing, which may disrupt the perception of low-level social cues and, in turn, compromise broader social cognitive processes. Here, we examined relations between basic visual processing and different levels of social cognition in a transdiagnostic youth sample. METHODS: A sample of 148 youth, ranging from healthy individuals to individuals with neuropsychiatric diagnoses and significant social dysfunction, completed two measures of basic visual processing (contrast sensitivity and visual integration) and a battery of social cognition tasks spanning lower-level (gaze perception) to mid-level (emotion recognition) to higher-level (theory of mind) social cognition. We used a four-level path model to test whether basic visual processing predicts gaze perception, which in turn predicts emotion recognition, which predicts theory of mind. RESULTS: Poorer contrast sensitivity and visual integration were associated with less precise gaze perception, which was, in turn, associated with worse emotion recognition, which was associated with worse theory of mind. This four-level path model demonstrated good fit and showed superior fit compared to alternative models. CONCLUSIONS: These findings suggest that basic visual processing influences the perception of basic social cues (e.g. gaze direction), which subsequently impairs more complex social perception and inference. Notably, this study extends prior observations from individuals with chronic schizophrenia to a transdiagnostic youth sample, indicating that altered basic visual processing may be a shared mechanism contributing to social cognitive deficits across psychiatric disorders and illness stages.
The DSM needs more than revision: five blind spots and a case for dialogical redesign.
Veldmeijer L, Batstra L, Van Os J
Psychol Med · 2026 May · PMID 42131991 · Full text
BACKGROUND: Recent proposals for revising the Diagnostic and Statistical Manual of Mental Disorders (DSM) aim to improve psychiatric diagnosis. While these efforts reflect substantial ambition, they continue to operate w...
BACKGROUND: Recent proposals for revising the Diagnostic and Statistical Manual of Mental Disorders (DSM) aim to improve psychiatric diagnosis. While these efforts reflect substantial ambition, they continue to operate within assumptions embedded in the DSM's underlying classificatory logic. This editorial examines whether such incremental revision is sufficient. METHODS: We provide a critical analysis of the recently published DSM roadmap and accompanying subcommittee commentaries. Drawing on contemporary literature, we identify five structural blind spots in the current reform agenda: public mental health, scientific inference, lived experience, epistemic governance, and the function of diagnosis. Based on this analysis, we propose an alternative dialogical redesign for the DSM. RESULTS: We argue that current revision considerations risk increasing complexity without resolving fundamental limitations in psychiatric classification. Specifically, our analysis highlights several areas that warrant further consideration, including the relationship between diagnostic expansion and societal conditions, the applicability of group-level scientific findings to individual care, the incorporation of experiential knowledge, participatory governance in revision processes, and the identity-related implications of diagnosis. In response, we propose redesigning the DSM as a hybrid dialogical system that retains coarse-grained classificatory categories for pragmatic purposes while shifting diagnostic practice toward contextual interpretation, collaborative meaning-making, relational understanding, and individualized care formulation. CONCLUSIONS: The challenges facing psychiatric diagnosis require more than incremental refinement. We therefore argue for a dialogical redesign of the DSM that better reflects the context-dependent, experiential, and relational nature of mental health conditions, positioning diagnosis as a starting point for collaborative inquiry.
Heterogeneous pathways to depressive and anxiety disorders: A cluster-based predictive study in a nationwide longitudinal cohort.
Chen C, Asai Y, Mochizuki Y … +4 more , Hagiwara K, Okubo R, Nakagawa S, Tabuchi T
Psychol Med · 2026 May · PMID 42130384 · Full text
BACKGROUND: Early prediction of depressive and anxiety disorders is challenging due to substantial heterogeneity in risk pathways. Conventional machine-learning models trained on aggregated populations may obscure subgro...
BACKGROUND: Early prediction of depressive and anxiety disorders is challenging due to substantial heterogeneity in risk pathways. Conventional machine-learning models trained on aggregated populations may obscure subgroup-specific mechanisms and limit interpretability for prevention. We evaluated whether a hybrid unsupervised-supervised framework can identify meaningful subgroups and yield more interpretable risk prediction. METHODS: We analyzed cohort data of 15,897 Japanese adults who completed baseline (August-September 2020) and 6-month follow-up (February-March 2021) surveys and did not screen positive for depressive and anxiety disorders at baseline (K6 score < 13). Using 169 baseline demographic, psychosocial, lifestyle, and behavioral variables, we performed hierarchical clustering to derive data-driven subgroups. Within each cluster, we trained Random Forest models to predict incident screened depressive and anxiety disorders at follow-up (K6 ≥ 13) and interpreted predictors using SHapley Additive exPlanations (SHAP). RESULTS: The overall 6-month incidence was 6.23%. A five-cluster solution revealed two high-risk subgroups: an older-adult profile with poor quality of life (12.9%) and a working-parent profile characterized by work-family overload (29.8%). Compared with a global model trained on the full sample, the cluster-then-predict framework showed broadly similar overall performance but performed better in the highest-risk subgroup and revealed more differentiated predictor profiles. Loneliness, health-related quality of life, happiness, and personality traits predominated in clusters with moderate adversity, whereas lifestyle disruption (sleep, diet, and irregular routines) characterized the high-risk late-life subgroup and alcohol dependence and work-family burden characterized the high-risk working-parent subgroup. CONCLUSIONS: Addressing risk-factor heterogeneity before prediction may enable more interpretable, context-tailored prevention strategies.
Polysubstance use in adolescents: conceptual issues and the need for a new public health framework and approach.
Fleury R, Staines L, Smyth B … +1 more , Cannon M
Psychol Med · 2026 May · PMID 42130292 · Full text
Polysubstance use is increasingly the norm among adolescents who use substances, yet research and clinical frameworks remain concentrated in single-substance models. This narrative conceptual editorial highlights key eme...
Polysubstance use is increasingly the norm among adolescents who use substances, yet research and clinical frameworks remain concentrated in single-substance models. This narrative conceptual editorial highlights key emerging literature on the conceptual inconsistencies and methodological challenges in polysubstance use research, particularly in the context of shifting cannabis legislation and adolescent vulnerability. A lack of definitional consensus, regarding the number of substances, timing of engagement, and intent of substances used, undermines the comparability of findings and the effectiveness of interventions. Adolescent polysubstance use is shaped by developmental, social, and structural factors, with cannabis and nicotine frequently overlooked despite their prevalence. This editorial addresses three linked gaps: definitional inconsistencies, insufficient attention to timing and intent of co-use, and the continued dominance of single-substance research frameworks. Therefore, we argue for clearer definitions, inclusive research designs, and interdisciplinary approaches.
Shared genetic architecture of gray matter deficits in schizophrenia and bipolar disorder: evidence from structural neuroimaging-genetic analyses.
Xie Y, Du J, Jiang Y … +4 more , Zhao Y, Lin S, Zhu W, Cao D
Psychol Med · 2026 May · PMID 42130287 · Full text
BACKGROUND: Schizophrenia (SCZ) and bipolar disorder (BD) share substantial clinical and neuroanatomical features, yet the neurogenetic basis underlying their shared gray matter volume (GMV) deficits remains poorly under...
BACKGROUND: Schizophrenia (SCZ) and bipolar disorder (BD) share substantial clinical and neuroanatomical features, yet the neurogenetic basis underlying their shared gray matter volume (GMV) deficits remains poorly understood. METHODS: We conducted meta-analyses to identify convergent GMV alterations across the two disorders. Genome-wide association studies (GWAS) were performed to uncover genetic variants associated with the shared GMV deficits region in UK Biobank participants. Polygenic risk score (PRS)-GMV associations were analyzed to examine the cumulative influence of genetic risk on GMV in regions with shared deficits. Furthermore, pleiotropic SNPs jointly associated with SCZ, BD, and shared GMV deficits were identified. Spatiotemporal gene expression profiling was utilized to characterize the developmental trajectories, and molecular docking was performed to explore potential drugs. RESULTS: Meta-analysis revealed consistent overlapping GMV reductions in frontal, temporal, and insular regions across SCZ and BD, based on 6,620 patients and 7,762 controls. GWAS identified 14 SNPs associated with the shared GMV deficits. PRS analyses showed that modestly higher SCZ polygenic risk correlated with decreased GMV of shared regions. Two pleiotropic SNPs - rs11191368 and rs79668541 - were linked to both disorders and the shared GMV deficits. Spatiotemporal expression analyses demonstrated distinct developmental trajectories, and molecular docking highlighted 168 drugs with binding interactions for shared genes. CONCLUSIONS: This study delineates shared neurogenetic mechanisms linking GMV abnormalities to genetic risk across SCZ and BD. Given the cross-sectional design, future longitudinal studies in independent cohorts are warranted to validate these findings and clarify the temporal relationships.
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