Journal Of Affective Disorders[JOURNAL]
Sun
200 papers
Sex differences in the association between hazardous alcohol consumption and suicide mortality: A population-based cohort study in South Korea.
Baek SU, Yoon JH
J Affect Disord · 2026 Oct · PMID 42190892 · Publisher ↗
BACKGROUND: While the co-occurrence of hazardous alcohol consumption and mental health problems has been well documented, evidence on sex-specific associations between hazardous alcohol consumption and suicide mortality...
BACKGROUND: While the co-occurrence of hazardous alcohol consumption and mental health problems has been well documented, evidence on sex-specific associations between hazardous alcohol consumption and suicide mortality remains limited. This cohort study explored the relationship between hazardous alcohol consumption and suicide mortality among men and women. METHODS: A nationally representative sample of 64,756 adults (27,726 males and 37,030 females) was followed until December 31, 2022, using data from a national death registry. Hazardous alcohol consumption was measured using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Participants were classified into non-alcohol use, low-risk alcohol consumption, and hazardous alcohol consumption groups. Deaths caused by intentional self-harm (ICD-10 codes X60-X84) were classified as suicide mortality. Sex-stratified Cox regression models were applied to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.67 years, 190 suicidal deaths occurred. Higher AUDIT-C scores were positively associated with the risk of suicide mortality among women (HR: 1.15, 95% CI: 1.03-1.28) but not among men (HR: 1.02, 95% CI: 0.95-1.09). In analyses in which alcohol use status was categorized, hazardous alcohol consumption was not linked to suicide mortality among men (HR: 1.01, 95% CI: 0.57-1.79), whereas hazardous alcohol consumption had a 2.50-fold (95% CI: 1.18-5.32) higher risk for suicidal mortality among women, compared with non-alcohol use. CONCLUSIONS: Hazardous alcohol consumption was linked to an increased risk of suicide mortality, particularly among women. This study underscores the need for sex-specific approaches to suicide prevention, particularly targeting women who engage in hazardous alcohol consumption.
Multimodal digital phenotyping of bipolar disorder subtypes: Differences between bipolar disorder I and II based on passive and active behavioral features from smartphones.
Faurholt-Jepsen M, Hammershøi DE, Bruun CF … +2 more , Bardram JE, Kessing LV
J Affect Disord · 2026 Oct · PMID 42190891 · Publisher ↗
BACKGROUND: Distinguishing between bipolar disorder type I and II constitutes a significant clinical challenge that relies on retrospective patient recall. Misclassification carries risks of inappropriate pharmacological...
BACKGROUND: Distinguishing between bipolar disorder type I and II constitutes a significant clinical challenge that relies on retrospective patient recall. Misclassification carries risks of inappropriate pharmacological management. Digital phenotyping offers a potential objective solution by monitoring behavioral biomarkers via smartphones. This study evaluated whether passive sensing data alone, or a multimodal approach combining active and passive data, could distinguish between bipolar disorder type I and II at the population level versus the individual level. METHODS: Analyses were conducted on data from 156 patients with newly diagnosed bipolar disorder participating in the Aspirin Bipolar RCT. Passive sensor data from smartphones, including GPS mobility and accelerometer activity metrics, were collected over a six- to twelve-month period. Linear Mixed-Effects Models were employed to analyze population-level differences in behavioral features, controlling for age, sex, and treatment allocation. Machine learning performance was assessed using Explainable Boosting Machines in both generalized (across-patient) and personalized (within-patient) paradigms. RESULTS: No statistically significant differences in passive behavioral features were found between bipolar disorder type I and II after accounting for multiple testing. However, demographic factors were predictors of behavior: older age was associated with lower sleep fragmentation (p < 0.001), and female sex was associated with a higher proportion of time still (p = 0.007). Consistent with these findings, generalized machine learning models failed to outperform chance at classifying bipolar disorder type (AUC ≈ 0.53). In contrast, personalized models trained on individual data achieved higher discriminative power. A personalized model relying solely on passive sensing achieved an AUC of 0.77, whereas a multimodal model incorporating passive data, active self-reports, and demographic factors reached an AUC of 0.96. CONCLUSION: Personalized multimodal digital phenotyping models achieved high performance in distinguishing between bipolar I and II, demonstrating the potential of smartphone-based passive sensing to support diagnostic differentiation at the individual level. However, passive sensing alone yielded substantially lower predictive power. This discriminative power did not generalize across populations, suggesting the absence of a universal digital fingerprint distinguishing bipolar subtypes at the population level. Behavioral markers in bipolar disorder appear to be highly idiosyncratic and strongly influenced by demographic variables. Future clinical applications of digital phenotyping should prioritize personalized modeling approaches that account for individual behavioral baselines.
From emotional dysregulation to violence: Psychological pathways associated with aggressive behavior.
Wang H, Amin S
J Affect Disord · 2026 May · PMID 42190890 · Publisher ↗
BACKGROUND: Violence and hostile behavior are major public health problems worldwide. Emotional dysregulation is now seen to be a major psychological mechanism driving violent behavior, yet the processes by which it func...
BACKGROUND: Violence and hostile behavior are major public health problems worldwide. Emotional dysregulation is now seen to be a major psychological mechanism driving violent behavior, yet the processes by which it functions are still not well known. OBJECTIVE: This study examined the mechanisms by which emotional regulation is linked to violent behavior, the moderating effect of impulsivity and chronic stress, and the moderating effect of affective instability. METHOD: We measured emotional dysregulation (DERS), violent behavior (Modified Conflict Tactics Scale), impulsivity (UPPS-P), affective instability, and chronic stress using a cross-sectional design and a nationally representative sample consisting of 1847 participants (M age = 32.4 years, SD = 11.2, 52.3% female). The moderated mediation model was tested using hierarchical regression, structural equation modeling, and bootstrapped mediation analyses (5000 resamples). RESULTS: A direct correlation was observed between emotional dysregulation and violent behavior (R = 0.34, 95% CI [0.29, 39]), indicating that 28.7% of the variance was due to emotional regulation. This relationship was mediated by impulsivity (indirect effect = 0.12, 95% CI [0.08, 0.17]) and chronic stress (indirect effect = 0.09, 95% CI [0.05, 0.14]). This association was moderated by affective instability (=0.18, p < .001) at high levels. The integrated moderated mediation model attributed 43.6% of the variance on violent behavior, including demographic covariates, direct effect, as well as parallel mediators, moderating by affective instability. CONCLUSION: Findings indicate that blended intervention strategies that focus on emotional control skills, impulse control and stress management might be applicable in violence prevention programs especially among individuals that are highly affective and unstable.
Association of age and cardiometabolic risk factors with cardiac diastolic function change in patients with bipolar disorder.
Hsiao CY, Lin YK, Lai HY … +5 more , Hsieh KL, Chung KH, Chiang SJ, Tsai SY, Chen PH
J Affect Disord · 2026 Oct · PMID 42190889 · Publisher ↗
BACKGROUND: Asymptomatic diastolic dysfunction is associated with heart failure and reduced survival. Few studies have evaluated the cardiac diastolic function of patients with bipolar disorder (BD) or examined the risk...
BACKGROUND: Asymptomatic diastolic dysfunction is associated with heart failure and reduced survival. Few studies have evaluated the cardiac diastolic function of patients with bipolar disorder (BD) or examined the risk factors associated with asymptomatic diastolic dysfunction. METHODS: A total of 127 individuals (65 BD and 62 mentally healthy controls) under age 45 without a clinical diagnosis of heart failure were recruited to undergo conventional and speckle-tracking echocardiography. Echocardiographic procedures were performed in accordance with the recommendations of the American Society of Echocardiography. Cardiometabolic risk factors were obtained using standard in-hospital examinations. RESULTS: Compared with the mentally healthy group, the BD group had significantly lower values of E velocity (Cohen d = 0.40), septal e' velocity (Cohen d = 0.65), average e' velocity (Cohen d = 0.41), and E/A ratio (Cohen d = 0.42) and a higher value (i.e., greater impairment) of left atrial conduit strain (Cohen d = 0.38). Multiple linear regression analysis revealed that age, diastolic blood pressure, serum fasting insulin, homeostasis model assessment of insulin resistance, and body mass index were significantly associated with poorer diastolic function in the BD group, whereas lithium use was associated with better diastolic function and a lower left ventricular mass index. CONCLUSION: Increased age and cardiometabolic risk factors are associated with poorer diastolic function in individuals with BD. The findings underscore the importance of integrating proactive cardiometabolic interventions into mental health-care programs designed for this at-risk group.
Witnessing trauma in the digital era: Uncensored media associates with posttraumatic stress in perinatal women.
Allouche-Kam H, Elhasid Felsenstein T, Arora IH … +4 more , Bartal A, Pham CT, Chan SJ, Dekel S
J Affect Disord · 2026 Oct · PMID 42190888 · Publisher ↗
BACKGROUND: Digital media increasingly shape how populations encounter large-scale traumatic events, enabling real-time exposure to uncensored graphic content among individuals not directly exposed. However, whether this...
BACKGROUND: Digital media increasingly shape how populations encounter large-scale traumatic events, enabling real-time exposure to uncensored graphic content among individuals not directly exposed. However, whether this form of indirect exposure is associated with posttraumatic stress responses, particularly following collective trauma, remains poorly understood. METHODS: We studied 630 perinatal women within the first months following the October 7, 2023, attacks and the Israel-Hamas War, none of whom were directly exposed to the attacks. Participants were assessed for posttraumatic stress disorder symptoms, demographic characteristics, psychosocial factors, and trauma exposure; geographic exposure (physical proximity to threat), interpersonal indirect exposure (e.g., knowing affected individuals), and media exposure (engagement with censored and uncensored trauma-related content). Hierarchical regression analyses examined the association between media exposure and PTSD symptom severity while accounting for relevant risk factors. RESULTS: 24.1% of the sample met criteria for probable PTSD. Intrusion and alterations in arousal and reactivity were the most frequently endorsed symptom clusters. Regression analysis revealed that greater exposure to uncensored traumatic video content was associated with higher PTSD symptom severity, after controlling for mental health history, psychosocial resources, religiosity, and other forms of trauma exposure (β = 0.153, p < 0.001), with media exposure explaining an additional 2.8% of the variance. CONCLUSIONS: Exposure to uncensored traumatic digital content was independently associated with greater PTSD symptom severity among perinatal women not directly exposed to the events. These findings suggest that digitally mediated exposure may represent an important contextual form of trauma exposure following collective trauma.
Temporal stability of depression symptom networks across cultures: Longitudinal analysis of MIDUS and MIDJA.
Fujii T, Seo T, Nogami Y
J Affect Disord · 2026 Oct · PMID 42190887 · Publisher ↗
BACKGROUND: The network approach to psychopathology conceptualizes mental disorders as systems with causally interacting symptoms. While the temporal stability of symptom networks has been examined in single-culture samp...
BACKGROUND: The network approach to psychopathology conceptualizes mental disorders as systems with causally interacting symptoms. While the temporal stability of symptom networks has been examined in single-culture samples, no research has compared stability patterns across cultural contexts. METHODS: Using longitudinal data from the Midlife in the United States (MIDUS; N = 673) and Midlife in Japan (MIDJA; N = 197), we estimated depression networks using four CES-D subscales (Depressed Affect, Positive Affect, Somatic Symptoms, Interpersonal Problems) at two time points (T1 and T2). Temporal stability was assessed using the Network Comparison Test and correlations between edge weights and centrality indices. RESULTS: Depression networks demonstrated high temporal stability in both samples, with edge weight correlations of r = 0.945 (MIDUS) and r = 0.902 (MIDJA) and centrality correlations of r = 0.957 (MIDUS) and r = 0.864 (MIDJA). Positive Affect showed moderate negative connections to other subscales in the American sample but was functionally independent in the Japanese sample across both time points. The Depressed Affect-Somatic connection was the strongest edge in both cultures but notably stronger in Japan. LIMITATIONS: The MIDJA sample was relatively small, measurement intervals differed between samples, and findings may not generalize beyond these specific midlife populations. CONCLUSIONS: Depression symptom networks show high temporal stability within cultures while exhibiting stable cross-cultural differences in specific-symptom connections. The functional independence of positive affect in Japanese samples has implications for cross-cultural assessments and culturally adapted interventions.
Suicide and self-harm in the age of generative artificial intelligence: The case of ChatGPT and rise of suicide-related lawsuits.
Ittefaq M, Arif R, Kamboh SA
J Affect Disord · 2026 Oct · PMID 42184938 · Publisher ↗
Self-harm and suicide trends have taken a new turn in the era of GenAI and communicative chatbots. Recent OpenAI's own report suggests that 1.2 million weekly ChatGPT users appear to be expressing suicidal thoughts, and...
Self-harm and suicide trends have taken a new turn in the era of GenAI and communicative chatbots. Recent OpenAI's own report suggests that 1.2 million weekly ChatGPT users appear to be expressing suicidal thoughts, and 80,000 users are potentially experiencing mania and psychosis. At the same time, OpenAI and other AI companies are facing lawsuits in several countries alleging that their chatbots encouraged vulnerable individuals to harm themselves. These lawsuits have sparked a growing scholarly debate about responsibility, safety, and the ethical use of chatbots in mental health services. GenAI can offer timely informational support and help identify suicide risk factors; it also presents significant risks, including the potential to amplify existing vulnerabilities and its inability to provide sustained care. Suicide prevention efforts now face novel challenges, with users, families, mental health professionals, psychiatrists, clinicians, and technology companies struggling to navigate rapidly evolving AI-mediated care. This article contended that researchers and clinicians should be cautious about the promises and pitfalls of GenAI around mental health support. We also discussed key considerations for designing and implementing ethical AI systems to strengthen transparency and regulations to develop humane technology that empowers users, families, and clinicians in promoting mental wellbeing.
Mirtazapine alleviates depressive-like behaviors through the paraventricular SIK1-CRTC1 signaling pathway.
Zhang H, Dong H, Xi Z … +3 more , Yan Z, Zhang Y, Zhang L
J Affect Disord · 2026 Oct · PMID 42184937 · Publisher ↗
BACKGROUND: The paraventricular nucleus (PVN) plays a pivotal role in integrating neuroendocrine responses to stress, with the salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) pathway cr...
BACKGROUND: The paraventricular nucleus (PVN) plays a pivotal role in integrating neuroendocrine responses to stress, with the salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) pathway critically regulating corticotropin-releasing hormone expression and hypothalamic-pituitary-adrenal (HPA) axis activity. Mirtazapine is a clinically effective antidepressant with a unique noradrenergic and specific serotonergic mechanism, yet whether its therapeutic actions involve modulation of this PVN pathway remains unexplored. METHODS: Adult male C57BL/6J mice were subjected to chronic social defeat stress (CSDS) or chronic unpredictable mild stress (CUMS), with mirtazapine (5 or 10 mg/kg, i.p.) administered for two weeks. Behavioral assessments included the forced swim test, tail suspension test, sucrose preference test, and social interaction test. HPA axis function was evaluated through plasma corticosterone and adrenocorticotropic hormone (ACTH) measurements. Molecular analyses of PVN tissue included western blotting, quantitative real-time PCR, co-immunoprecipitation, and immunofluorescence. AAV-mediated SIK1 knockdown in the PVN was employed to establish pathway necessity. RESULTS: Mirtazapine treatment effectively reversed chronic stress-induced behavioral deficits and normalized HPA axis hyperactivity. Chronic stress reduced SIK1 expression, increased total and nuclear CRTC1 levels, decreased cytoplasmic phosphorylated CRTC1, and enhanced CRTC1-CREB binding in PVN neurons-all of which were normalized by mirtazapine administration. Notably, SIK1 knockdown significantly attenuated mirtazapine's antidepressant-like effects and its ability to normalize HPA axis function. CONCLUSIONS: These findings identify the SIK1-CRTC1 system in the PVN as a critical mediator of mirtazapine's antidepressant-like actions, expanding our understanding of its therapeutic mechanism and reinforcing the relevance of this pathway as a target for depression treatment.
Stressed-out parenting brain: Effects of parenting stress, depression and anxiety on caregivers' brain structure and function.
Cheong Y, Lee S, Ro JH … +2 more , Bae J, Jung M
J Affect Disord · 2026 May · PMID 42184936 · Publisher ↗
BACKGROUND: Parenting stress (PS) arises when child-rearing becomes a stressor. Since the brain directs adaptation to stressors, we explored how the parenting brain adapts to PS in relation to depression and anxiety. MET...
BACKGROUND: Parenting stress (PS) arises when child-rearing becomes a stressor. Since the brain directs adaptation to stressors, we explored how the parenting brain adapts to PS in relation to depression and anxiety. METHOD: This study involved 167 primary caregivers (all mothers; mean [SD] age = 40.76 [3.09] years old) who completed the Parenting Stress Index (PSI) and Beck Depression/Anxiety Inventory (BDI/BAI) and underwent 3 T MR scanning. Structural and resting-state functional data were preprocessed using FreeSurfer and CONN. We conducted 1) partial correlation and multivariate linear regression analyses between psychological and brain structural measurements, and 2) seed-to-voxel analysis using left entorhinal cortex (L.ERC) as the seed. Lastly, structural equation modeling analyses were conducted to assess the statistical relationships between psychological and brain measurements. RESULTS: L.ERC surface area was negatively correlated with BDI (r = -0.255, p-adjusted = 0.035). Mediation analyses indicated that PSI subscales indirectly associated with L.ERC via parent characteristic domain and BDI, while BDI was directly negatively associated with L.ERC (β = -0.32, p = 0.001). Resting-state functional connectivity (RSFC) between L.ERC and a right occipital/precuneus cluster was negatively associated with BDI and PSI subscales. In the function-based model (fit: CFI = 0.993, RMSEA = 0.038), RSFCs loaded onto a latent brain function construct, and higher PS was associated with increased BDI, which in turn was associated with reduced RSFC (b = -0.36, p < 0.001). CONCLUSION: Structural and functional aspects of the parenting brain were associated with PS, in conjunction with depression, rather than anxiety, reflecting the cumulative and enduring neurobiological effects of depression over transient effects of anxiety.
Empirical examination of early maternal-infant bonding disturbances: Latent class analysis and development of a clinical decision rule.
Torres-Giménez A, Andrés-Perpiña S, Sureda-Caldentey B … +4 more , Gelabert-Arbiol E, Solé E, Garcia-Esteve L, Roca-Lecumberri A
J Affect Disord · 2026 Oct · PMID 42178029 · Publisher ↗
BACKGROUND: Early maternal-infant bonding is important for infant development and maternal caregiving, and disturbances in bonding are linked to adverse outcomes. Although Brockington et al. (2006) proposed a clinical fr...
BACKGROUND: Early maternal-infant bonding is important for infant development and maternal caregiving, and disturbances in bonding are linked to adverse outcomes. Although Brockington et al. (2006) proposed a clinical framework for bonding disturbances, these have not been examined using statistical classification methods. OBJECTIVE: To evaluate the construct validity of early maternal-infant bonding disturbances using latent class analysis (LCA) and to develop a clinically applicable decision rule. METHODS: A clinical sample of 211 postpartum mothers attending a specialised perinatal mental health unit was assessed using the Stafford Interview, the Postpartum Bonding Questionnaire (PBQ), and the Edinburgh Postnatal Depression Scale (EPDS). Thirteen dichotomous estimators derived from the Stafford Interview were entered into an LCA to identify latent classes. Associations with Brockington et al. (2006) categories and with clinical, psychosocial, and infant factors were examined. A decision rule was derived from the LCA results. RESULTS: Four latent classes were identified: normal bonding (55.5%), mild bonding disturbance (26%), mild bonding disturbance with anxiety (10%), and severe bonding disturbance (8.5%). Latent classes partially overlapped with Brockington et al. (2006) categories. Concordance between decision rule-based categories and LCA classes was good to very good (κ = 0.75-0.93). Classes were associated with PBQ scores, depressive symptoms, and difficult infant temperament. CONCLUSIONS: This study provides preliminary empirical support for the proposed classification of early maternal-infant bonding disturbances and suggests that a clinically applicable decision rule derived from LCA may be useful for their identification in specialist clinical settings.
Effect of continuation treatment on health-related quality of life in remitted psychotic depression.
Bendel RA, Alexopoulos GS, Marino P … +9 more , Meyers BS, Mulsant BH, Neufeld NH, Rothschild AJ, Voineskos AN, Whyte EM, Flint AJ, Bingham KS, STOP-PD II Study Group
J Affect Disord · 2026 Oct · PMID 42176815 · Publisher ↗
BACKGROUND: Continuation treatment with sertraline plus olanzapine is associated with lower risk of relapse of remitted psychotic depression than sertraline plus placebo. We examined the effect of continuation pharmacoth...
BACKGROUND: Continuation treatment with sertraline plus olanzapine is associated with lower risk of relapse of remitted psychotic depression than sertraline plus placebo. We examined the effect of continuation pharmacotherapy on health-related quality of life (HRQOL) in remitted psychotic depression. METHODS: One hundred and twenty-six men and women, aged 18 to 85 years, who had achieved sustained remission of psychotic depression with open-label treatment with sertraline plus olanzapine were randomized to continue sertraline plus either olanzapine or placebo. HRQOL was measured with the 36-item Short Form Health Survey (SF-36) at randomization baseline and study termination. The primary outcome was change in each of the eight SF-36 domains. Linear regression examined the relationship between randomized treatment and change in SF-36 domain scores. RESULTS: Sertraline plus olanzapine was associated with better outcomes in the Role Emotional (RE) and Mental Health (MH) domains than sertraline plus placebo. Relapse was associated with marked decline in both RE and MH scores. RE and MH scores at study termination were more than two standard deviations below the population mean in approximately one quarter of participants in the sertraline plus placebo group. CONCLUSIONS: In individuals with remitted psychotic depression, continuation treatment with sertraline plus olanzapine was associated with better outcomes in HRQOL domains directly relevant to mental health than treatment with sertraline plus placebo. These findings suggest that the benefit of sertraline plus olanzapine in preventing relapse of psychotic depression is associated with benefit in HRQOL.
Latent profile analysis of stress events and their association with anxiety and depression in first-year graduate students: A stress process theory perspective.
Qi X, Liang L, Yuan J … +3 more , Luo Y, Xu J, Meng H
J Affect Disord · 2026 Oct · PMID 42176814 · Publisher ↗
BACKGROUND: First-year graduate students experience substantial psychological burden, yet heterogeneity in stressor patterns remains unclear. Guided by Pearlin's stress process model, this study examined how multidimensi...
BACKGROUND: First-year graduate students experience substantial psychological burden, yet heterogeneity in stressor patterns remains unclear. Guided by Pearlin's stress process model, this study examined how multidimensional stressor configurations relate to anxiety and depressive symptoms and examined the indirect associations of coping style and personal mastery within these relationships. METHODS: A cross-sectional survey of 1654 first-year graduate students from five universities in Wuhan. Measures included stressful events, coping, personal mastery, social support, anxiety, and depression. Latent profile analysis identified subgroups based on four stress domains. Logistic regression and parallel mediation analysis examined profile differences and indirect associations. RESULTS: Three stressor profiles emerged: low-stress (61.5%), moderate-imbalance (27.4%), and high-stress (11.0%). Compared with the low-stress group, the moderate-imbalance and high-stress groups showed higher odds of anxiety (OR = 4.76 and 9.30) and depression (OR = 4.61 and 10.62). Academic and relational stressors showed the strongest associations with affective symptoms. Relative indirect association analyses suggested that personal mastery statistically explained 36% and 35.5% of the total relative associations for moderate-imbalance and high-stress profiles with anxiety, and 36.2% and 30.7% with depression. Coping showed small but statistically significant relative indirect associations only for depression (7.6-8.9%), while perceived social support showed no significant indirect associations. Direct associations remained significant after accounting for indirect associations. CONCLUSIONS: Graduate students exhibit distinct stressor profiles with differing mental health correlates. Elevated stress-particularly academic and relational strain-is associated with higher affective symptom risk, alongside lower personal mastery and adaptive coping. These hypothesis-generating findings may inform future intervention research.
Episode duration and severity as predictors of placebo response in major depressive disorder.
Peters EM, Quadri A, Aziz S … +1 more , Balbuena L
J Affect Disord · 2026 Oct · PMID 42176813 · Publisher ↗
The purpose of this study was to examine the effects of two patient-level factors, episode duration and severity, on placebo response in antidepressant clinical trials. To do this we conducted a secondary analysis of sev...
The purpose of this study was to examine the effects of two patient-level factors, episode duration and severity, on placebo response in antidepressant clinical trials. To do this we conducted a secondary analysis of seven 8-week, randomized, double-blind, placebo-controlled trials of desvenlafaxine (50-400 mg/d) for acute major depressive disorder (n = 3647). Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale. Subgroup variables were used to stratify participants according to episode severity (baseline depression score) and chronicity (episode duration ≥ 24 months). Effects on response rates were tested with logistic regression models. Chronicity and severity were unrelated; both variables were associated with lower placebo response rates, but neither moderated the efficacy of desvenlafaxine over placebo, as evidenced by nonsignificant subgroup-treatment interactions. Overall, the results suggest that chronicity and severity are general prognostic indicators and did not support the notion that drug-placebo differences could be meaningfully increased by selectively recruiting clinical trial participants based on these criteria.
Neural alterations in Pavlovian reversal learning link childhood trauma and transdiagnostic anxiety in youth.
DeCross SN, Kribakaran S, Odriozola P … +4 more , Sheridan MA, Tottenham N, Gee DG, McLaughlin KA
J Affect Disord · 2026 Oct · PMID 42176812 · Publisher ↗
BACKGROUND: Pavlovian reversal learning (RL) is a potential pathway linking childhood trauma (CT) with psychopathology. RL describes the ability to flexibly update associations of stimuli with threat and safety based on...
BACKGROUND: Pavlovian reversal learning (RL) is a potential pathway linking childhood trauma (CT) with psychopathology. RL describes the ability to flexibly update associations of stimuli with threat and safety based on changing contextual significance. This study aims to characterize how CT may alter the neural underpinnings of RL in youth in ways relevant to mental health. METHODS: One hundred participants aged 9-19, half with CT (i.e., interpersonal violence) exposure, completed a RL task during an fMRI scan. One previously-neutral stimulus was paired with an aversive stimulus and predicted threat (CS+); another was not and predicted safety (CS-). Then, contingencies were reversed, such that the old safety cue became the new threat cue (New CS+) and vice-versa. Regions-of-interest analyses and nonparametric mediation models with 10,000 simulations were used to examine patterns of neural activation and connectivity and whether they indirectly linked CT with psychopathology. RESULTS: Youth with CT displayed elevated threat RL (New CS+ > New CS-) in amygdala; reduced safety RL (New CS- > New CS+) in canonical safety-learning regions, including ventromedial prefrontal cortex, hippocampus, and posterior parahippocampal gyrus (PHG); and elevated hippocampus-anterior cingulate cortex connectivity during safety RL. Critically, there were indirect effects of CT on transdiagnostic psychopathology through reduced safety RL in hippocampus and PHG, such that trauma-related reductions in discrimination between reversed cues were associated with lower levels of generalized anxiety and panic symptoms, findings driven by associations within the trauma group. CONCLUSIONS: Alterations in RL following CT during this key developmental window may reflect an environmental experience-dependent pathway to resilience.
Evaluation of suicide behavior screening tools using machine learning and variable importance measures.
Carnes NC, Zouris J, Bryan CJ
J Affect Disord · 2026 Oct · PMID 42176811 · Publisher ↗
Suicide screening in military primary care settings is often conducted with a small number of self-report questions. The PRImary care Screening Methods (PRISM) study investigates how to enhance this screening's predictiv...
Suicide screening in military primary care settings is often conducted with a small number of self-report questions. The PRImary care Screening Methods (PRISM) study investigates how to enhance this screening's predictive validity by supplementing the standard approach with additional questions. The present research uses machine learning, specifically random forests implementing undersampling with discretized data, to characterize the most important risk/protective factors. An analysis of 1522 PRISM participants using 875 features identified suicide attempts up to 12 months post-baseline with 68.7% out-of-bag accuracy. The top five features identified using variable importance measures (VIMs) included: (1) "trouble falling or staying asleep, or sleeping too much"; (2) "have had nightmares about it or thought about it when you did not want to" with respect to a traumatic event; (3) "organization of time" as a life stressor; (4) "have you ever had thoughts of killing yourself"; and (5) "feel like people laugh at you." For each of these, bootstrapped risk ratios revealed that endorsement of the first response option (indicating strong disagreement) served as a protective factor. The most important risk factor identified-endorsing "feel like people laugh at you" with the last response option (indicating strong agreement)-increased both the sensitivity and specificity of primary care suicide screening when used as a supplement to the standard approach. These findings highlight the under-appreciated role of self-conscious emotions and sleep dysregulation in suicidal behavior and reveal the utility of machine learning methods for improving the identification of those at risk for suicidal behavior.
Trajectory classes of post-stroke depression severity and their baseline predictors: A multi-cohort replication study.
Thurston MD, Mattingley JB, Lo JW … +5 more , Sachdev PS, Desmond DW, Traykov L, Mehrabian S, Oestreich LKL
J Affect Disord · 2026 Oct · PMID 42176810 · Publisher ↗
Post-stroke depression (PSD) affects approximately one-third of stroke survivors and is associated with poorer rehabilitation outcomes, increased disability, and higher mortality. Despite its clinical importance, PSD is...
Post-stroke depression (PSD) affects approximately one-third of stroke survivors and is associated with poorer rehabilitation outcomes, increased disability, and higher mortality. Despite its clinical importance, PSD is often studied as a binary outcome, obscuring heterogeneity in symptom trajectories over time. This study aimed to identify replicable longitudinal trajectories of PSD across independent cohorts and examine baseline predictors of trajectory membership. Data were analysed from three cohorts of the Stroke and Cognition Consortium (STROKOG; n = 750). Depressive symptoms were measured using the Geriatric Depression Scale (GDS-15) and the Hamilton Depression Rating Scale (HAMD-17). Latent class growth analysis was conducted within cohorts and in pooled GDS-15 and HAMD-17 datasets. Across six analyses, a consistent three-class solution emerged. The majority of participants (58-83%) showed no clinically significant depressive symptoms (No Depression). A second class (14-29%) displayed mild symptoms that generally remitted over time (Mild Remitting). A smaller subgroup (4-13%) exhibited symptoms in the moderate-severity range throughout follow-up, with trajectory direction varying across analyses. Baseline global cognitive impairment predicted Mild Remitting class membership across both pooled analyses. In pooled HAMD-17 analyses, female sex predicted membership in the Moderate Improving class, characterised by moderately severe symptoms that gradually resolved over time. In pooled GDS-15 analyses, older age, hypertension, and diabetes predicted membership in the Moderate Stable class. PSD follows a robust three-trajectory structure across independent cohorts, countries, and instruments. Early clinical factors, particularly cognitive impairment, sex, and vascular risk factors, may identify stroke survivors at risk for persistent depressive symptoms, enabling earlier targeted intervention.
Risk prediction of depression- and anxiety-related psychological distress in a large multistage survey sample of Chinese adults: a multi-algorithm ensemble machine-learning model with SHAP.
Zang W, Liu N, Wu J … +2 more , Zhang Q, Wang J
J Affect Disord · 2026 Oct · PMID 42173369 · Publisher ↗
OBJECTIVE: To develop an interpretable ensemble machine-learning model to support risk stratification of elevated depression- and anxiety-related psychological distress in a large multistage survey sample of Chinese adul...
OBJECTIVE: To develop an interpretable ensemble machine-learning model to support risk stratification of elevated depression- and anxiety-related psychological distress in a large multistage survey sample of Chinese adults, and to examine nonlinear associations with key psychosocial factors. METHODS: We analysed an unweighted analytical sample of 10,294 adults from the China Social Mentality Survey. Psychological distress was measured with the Kessler-10 scale, and 13 psychosocial indicators were included as candidate predictors. The sample was split 7:3 into training and hold-out test sets. Six binary classifiers were trained and combined using a TOPSIS-weighted classifier fusion (TCF) ensemble. SHAP with LOWESS was used to examine feature importance and dose-response patterns. RESULTS: The TCF model showed the most balanced overall performance across metrics. SHAP analyses showed that loneliness and dehumanization experiences were the strongest risk features, whereas positive psychosocial resources were generally associated with lower predicted risk. SHAP-LOWESS curves indicated nonlinear dose-response relationships: predicted risk rose when key adverse psychosocial features exceeded specific thresholds, whereas several positive resources showed protective patterns within certain ranges. CONCLUSIONS: In a large unweighted multistage survey sample of Chinese adults, the TCF ensemble model provided an interpretable and balanced prediction framework for depression- and anxiety-related psychological distress and highlighted loneliness, dehumanization, and psychosocial resources as key correlates of elevated distress risk. These nonlinear patterns and thresholds may inform future risk assessment and prioritisation of psychosocial assessment, but require confirmation in longitudinal, externally validated, and design-weighted cohorts.
Comparison of digital gait characteristics measured by wearable devices in older adults with and without depressive symptoms.
Sun S, Zuo Y, Zhang L … +7 more , Song Y, Zhang Y, Shi H, Shen J, Zhang C, Zeng P, Fan G
J Affect Disord · 2026 Oct · PMID 42173368 · Publisher ↗
BACKGROUND: As older adults with depression exhibit gait impairments, this study aimed to investigate the association between depressive symptoms in older adults and digital gait parameters derived from wearable devices....
BACKGROUND: As older adults with depression exhibit gait impairments, this study aimed to investigate the association between depressive symptoms in older adults and digital gait parameters derived from wearable devices. METHODS: 862 community-dwelling older adults were recruited. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). A multi-sensor wearable gait analyzer was used to measure periodic, kinetic, and spatiotemporal gait parameters during a 12-m normal walking test. Multivariable logistic regression analyses were conducted to examine the relationship between depressive symptoms and Z-transformed gait parameters, adjusting for demographics, BMI, lifestyles, cognitive function, and comorbidities. Receiver operating characteristic curve analysis was used to evaluate the discriminative performance of gait parameters in identifying depressive symptoms. RESULTS: The mean age of all participants was 70.24 ± 6.19 years, and 58.35% were female. After adjusting for all covariates, longer double-limb support time (OR = 1.30, 95% CI: 1.05-1.60, P = 0.014) and terminal limb support time (OR = 1.26, 95% CI: 1.03-1.54, P = 0.023) were associated with higher odds of depressive symptoms. Conversely, higher thigh swing work (OR = 0.75, 95% CI: 0.59-0.95, P = 0.016), ground reaction force (OR = 0.79, 95% CI: 0.63-0.99, P = 0.041), landing control force (OR = 0.79, 95% CI: 0.63-0.99, P = 0.045), gait speed (OR = 0.63, 95% CI: 0.49-0.80, P < 0.001), stride frequency (OR = 0.78, 95% CI: 0.63-0.95, P = 0.016), step length (OR = 0.59, 95% CI: 0.46-0.75, P < 0.001), and stride length (OR = 0.59, 95% CI: 0.47-0.76, P < 0.001) were related to lower odds of depressive symptoms. Gait parameters demonstrated acceptable value for identifying depressive symptoms, with an area under the curve (AUC) of 0.707. Spatiotemporal parameters (AUC = 0.675) showed better discriminatory ability than periodic parameters (AUC = 0.585) and kinetic parameters (AUC = 0.609). CONCLUSION: Older adults with depressive symptoms exhibited poorer kinetic and spatiotemporal gait performance. Gait parameters measured by wearable sensors hold potential value for identifying depression.
Emotion regulation difficulties in adults with ADHD and associations with insomnia symptoms.
Sørensen L, Hjo C, Vollsund AE … +8 more , Flo-Groeneboom E, Jensen DA, Tømmeraas AM, Holmen N, Becker SP, Sonuga-Barke EJS, Bjorvatn B, Tamnes CK
J Affect Disord · 2026 Oct · PMID 42173367 · Publisher ↗
OBJECTIVES: Adults with attention-deficit/hyperactivity disorder (ADHD) frequently experience both emotion regulation difficulties and sleep disturbances. Although theories of insomnia and studies in non-ADHD samples sug...
OBJECTIVES: Adults with attention-deficit/hyperactivity disorder (ADHD) frequently experience both emotion regulation difficulties and sleep disturbances. Although theories of insomnia and studies in non-ADHD samples suggest a link between poor emotion regulation and insomnia, this relationship is understudied in ADHD. We examined whether difficulties regulating emotions were associated with insomnia symptoms in adults with ADHD, and whether this association was moderated by gender, age (<30 or ≥30 years), or eveningness preference. METHODS: A cross-sectional online survey was distributed in collaboration with the Norwegian ADHD Association. Of 1541 respondents, 1414 adults with self-reported ADHD diagnosis (81% female; ages 16-74; years, M age = 40 years) met inclusion criteria. Participants completed measures of emotion regulation, insomnia symptoms, chronotype, and sociodemographic and clinical characteristics, including education level, occupational status, ADHD symptoms, depression, anxiety, substance use, medication use, and comorbid conditions. RESULTS: Multiple linear regression analyses showed that greater emotion regulation difficulties, especially limited access to effective regulation strategies, were associated with more insomnia symptoms. Associations remained significant after controlling for sociodemographic and clinical characteristics. The association between emotion regulation difficulties and more insomnia symptoms was stronger (medium effects) among emerging adults (<30 years) than older adults (small effects). No moderation effects were found for gender, age as a continuous moderator, or eveningness preference. CONCLUSIONS: Difficulties in adaptively regulating emotional states, a common challenge in ADHD, were linked to more insomnia symptoms. These findings underscore the importance of assessing and addressing sleep disturbances in adults with ADHD, particularly among those with emotion regulation difficulties.
Light, serotonin, neurosteroids, and activation states in bipolar-spectrum mood disorders: a circadian-informed framework.
Fornaro M, Carta MG
J Affect Disord · 2026 Oct · PMID 42167699 · Publisher ↗
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