Journal Of Affective Disorders[JOURNAL]
Sun
200 papers
Childhood violence exposure and the risk of multimorbidity in middle-aged and older adults: A multi-cohort study.
Zhang W, Wu J, Deng L … +2 more , He F, Liang Y
J Affect Disord · 2026 Jun · PMID 42248533 · Publisher ↗
OBJECTIVE: To investigate the longitudinal associations between childhood violence exposure and the risk of depressive symptoms and multimorbidity in middle-aged and older adults using two ageing cohorts. METHODS: Data w...
OBJECTIVE: To investigate the longitudinal associations between childhood violence exposure and the risk of depressive symptoms and multimorbidity in middle-aged and older adults using two ageing cohorts. METHODS: Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020) and the English Longitudinal Study of Ageing (ELSA, 2007-2020). After exclusions, 5417 (CHARLS) and 1789 (ELSA) participants were analyzed using multilevel regression, Cox proportional hazards, and mediation models. RESULTS: The proportion with depressive symptom-multimorbidity comorbidity increased over follow-up. Exposed individuals had higher depression scores, more chronic conditions, and greater comorbidity rates than unexposed counterparts. After adjusting for demographic and socioeconomic factors, childhood violence exposure remained a significant risk factor for depressive symptoms (CHARLS: HR = 1.30, 95% CI: 1.22-1.39; ELSA: HR = 1.52, 95% CI: 1.30-1.78), multimorbidity (CHARLS: HR = 1.19, 95% CI: 1.10-1.28; ELSA: HR = 1.15, 95% CI: 1.01-1.31), and comorbidity (CHARLS: HR = 1.37, 95% CI: 1.26-1.48; ELSA: HR = 1.45, 95% CI: 1.21-1.72). Mediation analyses showed that the association with multimorbidity was partly via depressive symptoms (proportion mediated: CHARLS 14.35%, ELSA 15.20%; both P < 0.05), and the association with depressive symptoms was partly via multimorbidity (CHARLS 19.46%, ELSA 10.05%; both P < 0.05). CONCLUSION: Childhood violence exposure is a significant risk factor for depressive symptoms, multimorbidity, and their comorbidity in middle-aged and older adults. The temporal pathways linking depressive symptoms and chronic conditions may partly account for this association. Early identification and integrated interventions are essential for mitigating the long-term comorbidity burden and promoting healthy ageing.
Parental but not child reports of affective lability in offspring predict conversion to bipolar disorder in youth at increased genetic risk.
Roberts G, Ratheesh A, Fullerton JM … +11 more , Cignarella C, Francis E, Kamali M, Stapp EK, Ghaziuddin N, Hulvershorn L, McInnis MG, Wilcox HC, Edenberg HJ, Nurnberger JI, Mitchell PB
J Affect Disord · 2026 Jun · PMID 42248532 · Publisher ↗
BACKGROUND: The identification of clinical risk factors in individuals at genetic risk of developing bipolar disorder (BD), and who subsequently go on to develop BD, may enable targeted early intervention. Affective labi...
BACKGROUND: The identification of clinical risk factors in individuals at genetic risk of developing bipolar disorder (BD), and who subsequently go on to develop BD, may enable targeted early intervention. Affective lability has been reported to be increased in youth at familial risk of psychiatric illness, and to predict onset of BD in prospective studies. However, parent-reported and child self-reports of affective instability may be discrepant. METHODS: We measured affective lability at baseline using both the self- and parent-reported versions of the Children's Affective Lability Scale (CALS) in a multisite (US and Australian) cohort of 315 young unaffected individuals, aged 12-21, at high familial risk of BD (HR), 165 controls, and 13 patients with established BD. New onsets of threshold and subthreshold BD were assessed prospectively. RESULTS: Parental, but not child, reports of affective lability at baseline were significantly higher in HR who later developed first onset of either threshold (N = 12) or subthreshold BD (n = 27); these differences were driven by irritability and anxiety/depression factors but not by the mania factor of the CALS. LIMITATIONS: While our study is well powered for whole group comparisons, the HR subgroup analyses (of threshold and subthreshold BD groups separately) were underpowered. CONCLUSION: Parental reports of affective lability in youth at increased familial risk to BD may assist clinicians in detecting individuals at elevated risk of converting to BD, but they do not constitute a validated clinical prediction tool.
Association between physical activity and suicidal ideation: Findings from the 1982 Pelotas (Brazil) birth cohort and an updated systematic review and meta-analysis.
Scholl CC, Jaccottet MB, Pecoits DOS … +5 more , di Gregorio M, Quevedo LA, Pinheiro RT, Motta JVDS, Horta BL
J Affect Disord · 2026 Jun · PMID 42248531 · Publisher ↗
BACKGROUND: Evidence on the impact of physical activity on suicidal ideation remains inconsistent. We examined this association in the 1982 Pelotas Birth Cohort (Brazil) and updated a systematic review and meta-analysis....
BACKGROUND: Evidence on the impact of physical activity on suicidal ideation remains inconsistent. We examined this association in the 1982 Pelotas Birth Cohort (Brazil) and updated a systematic review and meta-analysis. METHODS: In 1982, all births in Pelotas (southern Brazil) were identified and prospectively followed up. Leisure-time physical activity at age 23 was measured using the International Physical Activity Questionnaire, and suicidal ideation at age 30 was assessed using the Mini International Neuropsychiatric Interview. Odds ratios (OR) were estimated using logistic regression. For the systematic review, PubMed, CINAHL, and PsycArticles were searched for studies that assessed the relationship between physical activity as exposure and suicidal ideation as outcome. We estimated pooled OR using a random-effects model of studies reporting OR and prevalence ratios (PR). RESULTS: In the cohort (n = 3268), being sufficiently active was associated with lower odds of suicidal ideation in crude analysis (OR = 0.56, 95% CI 0.41-0.78) but the association vanished after adjustment for confounders (OR = 1.01, 95% CI 0.68-1.50). Seventy-two studies met inclusion criteria for the systematic review, of which 50 studies were meta-analyzed, yielding a pooled OR of 0.81 (95% CI 0.76-0.87; I = 94.9%). Associations were observed in cross-sectional studies (OR = 0.82, 95% CI 0.77-0.87) but not in cohort studies (OR = 1.00, 95% CI 0.80-1.25). CONCLUSIONS: Analysis conducted in the 1982 Pelotas Birth Cohort showed that controlling for confounding is crucial. Moreover, pooled estimates from prospective studies do not support a protective association, suggesting that physical activity may not be independently associated with suicidal ideation.
Smartphone-based cognitive assessment in older adults with depression: Feasibility and task performance using ecological momentary assessment.
Kaufman JR, Patrick RE, Ren B … +5 more , Maciarz J, Gregg A, Ozonsi R, Dickinson RA, Weisenbach SL
J Affect Disord · 2026 Jun · PMID 42248530 · Publisher ↗
INTRODUCTION: This study evaluated the feasibility of smartphone-based ecological momentary assessment (EMA) to test middle-aged and older adults' cognition - via tasks of processing speed and cognitive control -with and...
INTRODUCTION: This study evaluated the feasibility of smartphone-based ecological momentary assessment (EMA) to test middle-aged and older adults' cognition - via tasks of processing speed and cognitive control -with and without depression history. METHODS: Participants aged 55-79 (n = 79; 31 with depression history, 48 never-depressed controls) completed a 14-day EMA protocol with three daily assessments. The relevant tasks were Symbol Match Task (SMT; processing speed) and Go/No-Go task (GNG; cognitive control). Feasibility was evaluated through completion rates and missingness. Generalized additive modeling was used to evaluate associations between depression and cognitive performance, including trajectories, controlling for age, sex, and education. RESULTS: Of the 3318 possible response sessions, 2181 GNG and 2311 SMT were completed, nearly 70%. Controls demonstrated higher daily completion (GNG: 2.15 vs. 1.69 sessions, p = 0.035) and lower missingness (28% vs. 44%, p = 0.035) than depressed participants. Across tasks, depression history was associated with slower response times, less accuracy, and reduced efficiency. Controls averaged 2071 ms on SMT versus 2342 ms for depressed participants. Both groups showed performance improvements over time, suggesting learning effects, with parallel trajectories indicating a model consistent with depression's stable impact on cognitive functioning. CONCLUSIONS: While adherence challenges do exist, especially for those with a history of depression, smartphone-based EMA appears feasible for cognitive assessment in older adults. Depression impacts processing speed and cognitive control in this these real-world settings, and deficits persist regardless of current presence of symptoms. These findings support EMA's ecological validity for evaluating cognitive function and its potential for informing targeted interventions in late-life depression.
A network analysis of psychosocial risk factors and depression in adolescence.
Bužinel J, Norman J, Hughes-Nind J … +1 more , Carlisi C
J Affect Disord · 2026 Jun · PMID 42248529 · Publisher ↗
Adolescence is a period marked by social, psychological and physiological change, coinciding with a peak in depression onset. Over the last few decades, incidence of depression in adolescents has increased substantially,...
Adolescence is a period marked by social, psychological and physiological change, coinciding with a peak in depression onset. Over the last few decades, incidence of depression in adolescents has increased substantially, presenting a serious public health concern. The risk factors associated with depression have mostly been studied in isolation or without consideration for differences between age groups, limiting our ability to infer how factors are associated with each other and with depressive symptomatology. In the current study, we explored the relationships between different psychosocial risk factors and depression in adolescence, using cross-sectional data collected from adolescents aged 11-18 years (n = 202). We estimated two network models. The first focused on depression severity and the second on core depressive symptoms (low mood and anhedonia). In both networks, roughly half of all possible edges were estimated as non-zero (52.78% and 53.32%, respectively). Emotion regulation difficulties, perceived stress and school environment were among the most central factors and showed some of the strongest associations with both depression severity and presence of individual core symptoms. The network structure was largely independent of age, but the quality of school environment was more strongly related to depression severity in older adolescents. The study expands our understanding of the multivariate associations of risk factors and depression at different ages. The findings highlight emotion regulation, stress management skills and school environment as potential prevention and intervention targets, and point towards a need to consider differences between age groups when addressing depression in adolescence.
Prosocial behaviors across bipolar and major depressive mood disorders: A preliminary investigation.
Ibonie SG, Villanueva CM, Reddan MC … +7 more , Rosa L, Hargrove R, Weinstock LM, Carter M, Wager TD, Zaki J, Gruber J
J Affect Disord · 2026 Jun · PMID 42248528 · Publisher ↗
Bipolar and major depressive disorders are both serious and costly psychiatric disorders. Yet extant research largely focuses on social functioning impairments in mood disorders despite some work suggesting areas of adap...
Bipolar and major depressive disorders are both serious and costly psychiatric disorders. Yet extant research largely focuses on social functioning impairments in mood disorders despite some work suggesting areas of adaptive social functioning. The present study presents a preliminary investigation aiming to further examine distinct facets of prosocial behavior using previously validated survey and behavioral measures among a clinically diagnosed sample of adults with bipolar I disorder (BD; n = 19), major depressive disorder (MDD; n = 28) and non-psychiatric controls (CTL; n = 29). A subset of individuals with BD and MDD were prospectively followed at a 6-month and 12-month follow-up time point. Findings suggest that BD and MDD individuals did not differ in prosocial behavior across eight distinct measures compared to the CTL group. Follow-up findings suggest that prosocial behavior may be associated with better prospective social support outcomes in the MDD and BDD groups. Although these results are preliminary due to the modest sample size, they suggest that some aspects of prosocial behaviors may be preserved among individuals with bipolar and unipolar mood disorders.
Delineating genetic and environment effects on anxiety in adulthood: Application of a latent trait-state model.
Olatunji BO, Beam CR, Cole DA
J Affect Disord · 2026 Jun · PMID 42248527 · Publisher ↗
Although genetic and environmental factors play a key role in the long-term stability of anxiety, the extent to which the genetic and environmental determinants are best characterized by state- versus trait-like componen...
Although genetic and environmental factors play a key role in the long-term stability of anxiety, the extent to which the genetic and environmental determinants are best characterized by state- versus trait-like components is unclear. Also unclear is whether the genetic and environmental effects underlying trait and state components of anxiety differ across adult development. This study analyses data from twins (N = 4854) in the Washington State Twin Registry (WSTR) that completed a measure of anxious symptoms across seven waves during the COVID-19 pandemic in order to identify the genetic and environmental sources of stability and change in anxiety during adulthood. The sample was divided into three cohorts, representing early, middle, and late adulthood. Application of phenotypic latent trait-state models showed that the latent state component of anxiety accounted for most of the variance in young adulthood and late adulthood whereas the latent trait component accounted for the majority of variance in middle adulthood. Genetically informed models showed that nonshared environmental variance underlying the latent state component accounted for the greatest amount variance in early (50.99%) and late (88.50%) adulthood whereas genetic variance of the trait component accounted for the majority of variance (49.44%) in middle adulthood. These findings highlight different processes (i.e., state vs. trait) that account for stability of anxiety at different periods in adulthood.
Disparate plasma metabolomic profiles in late-life depression and amnestic mild cognitive impairment: A H NMR metabolomics study.
Gao Y, Hu JZ, Zhao MY … +8 more , Wang D, Xue KY, Du XZ, Wang X, Hu XD, Li JH, Zhang JH, Liu S
J Affect Disord · 2026 Jun · PMID 42248526 · Publisher ↗
OBJECTIVE: This study aims to delineate the plasma metabolic signatures of late-life depression (LLD) and amnestic mild cognitive impairment (aMCI), two prodromal populations at high risk for dementia, and to identify ca...
OBJECTIVE: This study aims to delineate the plasma metabolic signatures of late-life depression (LLD) and amnestic mild cognitive impairment (aMCI), two prodromal populations at high risk for dementia, and to identify candidate biomarkers for early intervention. METHODS: Plasma samples from 53 elderly participants (11 LLD, 26 aMCI, 16 healthy controls) were analyzed by H-nuclear magnetic resonance (H NMR) metabolomics. The differential metabolites were screened and correlated with neurocognitive scores, and then the diagnostic efficacy was evaluated by the receiver operating characteristic (ROC) curve. Finally, Mendelian randomization was used to verify the potential causal relationship between these candidate biomarkers and dementia. RESULTS: Both LLD and aMCI displayed marked metabolic perturbations, primarily affecting glycolysis/gluconeogenesis, galactose metabolism, and arginine biosynthesis. Scyllo-inositol was significantly elevated in LLD and reduced in aMCI. It discriminated LLD, aMCI, and healthy controls, and correlated with neurocognitive tests scores. Combination of scyllo-inositol with memory scales yielded promising diagnostic performance. Its AUC was 0.920 (95%CI: 0.808-1.000) for distinguishing LLD from HC, and 0.950 (95%CI: 0.892-1.000) for distinguishing aMCI from HC. There is a potential causal relationship between scyllo-inositol and dementia. CONCLUSION: These findings elucidate the metabolic link between LLD and aMCI and support a preliminary model combining plasma metabolites with cognitive testing for early identification and precise intervention in high-risk populations for dementia.
Predicting NSSI among Chinese transgender and gender diverse people: the role of social connectedness, internalized stigma, and self-esteem.
Guan L, Zhang X, Gao L … +6 more , Zhao Y, Yao H, Nie Z, Lu C, Li J, Tao Q
J Affect Disord · 2026 Jun · PMID 42242430 · Publisher ↗
BACKGROUND: Non-suicidal self-injury (NSSI) is highly prevalent among transgender and gender diverse (TGD) individuals. However, the mechanisms underlying the influence of psychosocial factors on NSSI remain unclear. Thi...
BACKGROUND: Non-suicidal self-injury (NSSI) is highly prevalent among transgender and gender diverse (TGD) individuals. However, the mechanisms underlying the influence of psychosocial factors on NSSI remain unclear. This study aims to explore the relationship between social connectedness, internalized stigma, self-esteem, and NSSI in TGD population. METHODS: The study was conducted from September 2024 to April 2025 among 770 TGD individuals in China (Mage = 25.55). First, we developed and validated an internalized stigma scale for TGD individuals (ISS-TGD) in the Chinese context. Second, a cross-sectional survey was conducted to investigate the relationship between social connectedness, internalized stigma, self-esteem, and NSSI. RESULTS: The developed 24-item ISS-TGD demonstrates excellent psychometric properties. The prevalence rate of NSSI among TGD individuals was 36.36%. Social connectedness (OR = 0.70, 95% CI [0.51, 0.97]), self-esteem (OR = 0.33, 95% CI [0.20, 0.55]) were significantly associated with NSSI. In addition, the relationship between social connectedness and NSSI was mediated by internalized stigma (manifested as stereotype endorsement, β = -0.119, 95% CI [-0.245, -0.019], p = 0.036; and stigma resistance, β = -0.143, 95% CI [-0.305, -0.021], p = 0.046) and self-esteem. Network analysis revealed that "scratching self intentionally" and "pinching self deliberately" were the primary NSSI methods. CONCLUSION: NSSI of TGD individuals is influenced by social connectedness, internalized stigma, and self-esteem. Enhancing social connectedness and self-esteem, and reducing internalized stigma are important for reducing NSSI, thereby improving mental health among TGD individuals.
Dual controllability de-differentiation of functional brain networks in major depressive disorder: Insights from large-scale neuroimaging and transcriptomic integration.
Ou M, Shen H, Liu W … +3 more , Su J, Zeng LL, Hu D
J Affect Disord · 2026 Jun · PMID 42242429 · Publisher ↗
Aberrant brain state transitions are a key neuropathological feature of major depressive disorder (MDD), yet the underlying mechanisms and associated transcriptional signatures remain poorly elucidated. Here, leveraging...
Aberrant brain state transitions are a key neuropathological feature of major depressive disorder (MDD), yet the underlying mechanisms and associated transcriptional signatures remain poorly elucidated. Here, leveraging the largest publicly available resting-state fMRI dataset (N = 1494; 778 patients, 716 controls), we applied network control theory to characterize abnormal state transition dynamics in MDD and examine their link to whole-brain gene expression. Global analyses revealed that although overall brain controllability was reduced in MDD, the spatial distribution pattern of controllability and its coupling with network topology were largely preserved relative to controls. At the network level, we identified a dual de-differentiation of controllability profiles in MDD: average controllability was significantly decreased in the visual and sensorimotor networks, accompanied by aberrant increases in the frontoparietal and salience networks. Conversely, modal controllability exhibited an inverse pattern in these networks. Integrating transcriptomic data from the human brain, we found that MDD-associated genes were significantly enriched within the transcriptional signature related to these controllability alterations. Specifically, genes linked to decreased average controllability were primarily enriched in pathways governing gene expression regulation, whereas those linked to its increase were enriched in synaptic signaling and plasticity pathways. Cell type-specific analyses further indicated that expression changes specific to excitatory and inhibitory neurons showed the strongest associations with the observed alterations in average controllability. Collectively, our findings bridge microscale molecular pathways with macroscale network dysfunction, providing a novel mechanistic framework for understanding the rigid brain dynamics in depression and may inform the identification of potential therapeutic targets.
Week-ahead prediction of depressive episodes using wearable-derived circadian biomarkers: A multicenter deep learning study with risk-based operating thresholds.
Kim B, Chae M, Seo H … +12 more , Jeong J, Park S, Jeong I, Kim Y, Kim Y, Jung T, Lee T, Cho CH, Yeom JW, Lee T, Lee HJ, Lee H
J Affect Disord · 2026 Jun · PMID 42242428 · Publisher ↗
Early detection of depressive episodes is important because shorter duration of untreated illness is associated with better outcomes, yet routine care remains largely reactive and dependent on retrospective self-report....
Early detection of depressive episodes is important because shorter duration of untreated illness is associated with better outcomes, yet routine care remains largely reactive and dependent on retrospective self-report. Wearables enable passive, continuous monitoring, and circadian disruptions in sleep-wake, activity, and diurnal heart rate (HR) patterns may precede mood episodes. However, prior wearable-based models often relied on short prediction horizons, simplistic circadian proxies, and limited clinical interpretability. We evaluated a deep learning approach that integrates two complementary circadian markers derived from a single wearable: an HR-derived cosine acrophase and a sleep-timing-based proxy measure of circadian phase related to dim-light melatonin onset (DLMO), since melatonin was not directly measured. Performance was summarized across risk-based operating thresholds. In a multicenter real-world mood disorder cohort (N = 144; 90,281 person-days), we trained a time-series model using 7-day wearable histories to predict the presence of a clinician-verified depressive episode one week ahead, with participant-level splits (6: 2:2) and discrimination consistency summarized across 10 repeated holdout runs. The combined circadian model achieved a mean area under the receiver operating characteristic curve (AUROC) of 0.772 (95% confidence interval [CI], 0.750-0.794). On the held-out test set, the top 20% of risk-ranked patient-days captured 63.5% of depressive-episode days; at a base prevalence of 5.3%, positive predictive value (PPV) was 16.7% (3.2-fold prognostic lift), with a review burden of 20 per 100 patient-days. These findings support the feasibility of wearable-based week-ahead depressive-risk stratification in mood disorders, although external validation, probabilistic calibration, transportability assessment, and prospective episode-onset evaluation are required before clinical implementation.
Unpacking the role of psychopathology in the state-to-trait mindfulness transition: A longitudinal structural equation modeling study.
O'Brien VL, Rickert NP
J Affect Disord · 2026 Jun · PMID 42235831 · Publisher ↗
OBJECTIVES: Research has established that higher trait mindfulness is inversely associated with psychopathology in cross-sectional and longitudinal studies, and research has also demonstrated that mindfulness-based inter...
OBJECTIVES: Research has established that higher trait mindfulness is inversely associated with psychopathology in cross-sectional and longitudinal studies, and research has also demonstrated that mindfulness-based interventions increase trait mindfulness over time. The present study sought to investigate the trajectory of mindfulness development by examining whether repeated practice of state mindfulness during the intervention cultivates trait mindfulness over time, and whether baseline psychopathology moderates this growth trajectory. METHODS: We recruited 274 participants to explore how psychopathology (i.e., anxiety, depression, trauma, and alcohol use) relate to the development of state mindfulness during a four-week, asynchronous online mindfulness-based reduction course. RESULTS: Using a latent growth curve model, key findings were that previous mindfulness experience predicted baseline state mindfulness (β = 0.324, p < .001); baseline anxiety positively predicted baseline state mindfulness (β = 0.420, p = .002) and negatively predicted growth in state mindfulness (β = -0.492, p = .047); and growth in state mindfulness positively predicted final trait mindfulness levels (β = 1.144, p = .035). CONCLUSIONS: These results suggest that individuals with higher anxiety may face challenges while engaging with mindfulness practice. The study contributes valuable insights into the dynamics of state mindfulness growth and highlights the potential interference of anxiety in the psychotherapeutic trajectory.
Duration-dependent transition from reversible to persistent depressive-like behaviors following chronic circadian misalignment: Involvement of impaired BDNF-TrkB signaling and myelin loss.
Li X, Yuan L, Zuo Y … +5 more , Li X, Jin T, Cheng L, Chu H, Zhang T
J Affect Disord · 2026 Jun · PMID 42235830 · Publisher ↗
BACKGROUND: Chronic circadian misalignment (CM) is increasingly implicated in the development of depression. However, the temporal progression of CM-induced neural dysfunction and the reversibility of associated myelin p...
BACKGROUND: Chronic circadian misalignment (CM) is increasingly implicated in the development of depression. However, the temporal progression of CM-induced neural dysfunction and the reversibility of associated myelin pathology remain poorly understood. PURPOSE: This study aimed to investigate how different durations of CM influence depressive-like behaviors, myelination, and oligodendrocyte (OL) development in mice, with particular emphasis on recovery potential and the involvement of brain-derived neurotrophic factor (BDNF) signaling. METHODS: Male C57BL/6 mice were exposed to a long-term variable photoperiod (L-VP) paradigm for 18, 36, or 54 days, followed by recovery under a normal light-dark cycle for 18 or 54 days. During recovery, a subset of mice received the BDNF mimetic 7,8-dihydroxyflavone (7,8-DHF). Behavioral and molecular analyses were used to assess depressive-like behaviors, OL lineage dynamics, myelination status, and BDNF-TrkB downstream signaling in the prefrontal cortex and hippocampus. RESULTS: CM induced duration-dependent depressive-like behaviors, reduced BDNF expression, impaired OL maturation, and myelin loss. Deficits caused by short- to intermediate-term CM (18 and 36 days) were largely reversible after circadian restoration, whereas prolonged CM (54 days) resulted in persistent myelin basic protein (MBP) reduction and sustained behavioral impairments, indicating a transition toward irreversible pathology. Activation of TrkB signaling via 7,8-DHF partially restored OL. CONCLUSION: This study elucidates the temporal dynamics of CM-induced depressive behaviors and myelin injury, and suggests that prolonged CM drives a transition from reversible dysfunction to persistent pathology. Targeting BDNF-TrkB signaling may represent a potential chronotherapeutic strategy for mood disorders associated with long-term circadian misalignment.
How machine learning applied on fMRI could improve the prognosis of the post-traumatic stress disorder: A systematic review.
Peyvandi A, Pigoni A, Anastasi A … +5 more , Nosari G, Borghi L, Vegni E, Brambilla P, Delvecchio G
J Affect Disord · 2026 Jun · PMID 42235829 · Publisher ↗
BACKGROUND: Post-traumatic stress disorder (PTSD) is a stressor-related disorder that affects a significant proportion of the population worldwide. Despite the neurological nature of this disorder, its functional biomark...
BACKGROUND: Post-traumatic stress disorder (PTSD) is a stressor-related disorder that affects a significant proportion of the population worldwide. Despite the neurological nature of this disorder, its functional biomarkers, due to mixed results remain far to be understood. Therefore, the present review study aims to explore functional brain differences between individuals with PTSD and healthy controls with (TEHC) and without (TUHC) trauma exposure, using a machine learning approach. METHOD: A systematic search was performed in PubMed, Embase, and Scopus to identify relevant studies published before 1st of November 2024. A total of 19 studies were included in our data extraction process. The paper has been registered on OSF (https://archive.org/details/osf-registrations-n6bc7-v1)/(https://osf.io/n6bc7/). RESULTS: Default mode and salience networks have been determinant in classifying PTSD participants from both TEHC and TUHC. However, middle frontal gyrus as well as sensory motor area were only involved in classifying PTSD participants from TEHC. Finally, the results have also shown that the association between left amygdala and hippocampus is determinant in identification of PTSD severity. LIMITATIONS: The analysis of the available literature was restricted due to the non-homogeneous characteristics of studies - both in terms of methodology and clinical aspects - which restricted our ability to draw comprehensive conclusions. In addition, some studies used overlapping samples therefore limiting the generalizability of the results. CONCLUSION: The identified networks play a crucial role in distinguishing PTSD participants from healthy participants. These findings could aid in developing more accurate diagnostic tools and may even help predict individuals at higher risk of developing PTSD following exposure to trauma events.
When love harms: Longitudinal effects of harsh parenting on adolescents' depressive symptoms and reactive-proactive aggression.
Hou Y, Song S, Guo R … +1 more , Li C
J Affect Disord · 2026 Jun · PMID 42229636 · Publisher ↗
BACKGROUND: Harsh parenting is linked to adolescent depressive symptoms and reactive-proactive aggression. The emotional mechanisms behind these links remain unclear, especially in Chinese culture. OBJECTIVE: This 3-year...
BACKGROUND: Harsh parenting is linked to adolescent depressive symptoms and reactive-proactive aggression. The emotional mechanisms behind these links remain unclear, especially in Chinese culture. OBJECTIVE: This 3-year longitudinal study examined whether sadness and anger rumination mediate the effects of harsh parenting on depressive symptoms and reactive-proactive aggression among Chinese adolescents, and whether these pathways differ by gender. METHOD: A total of 878 adolescents (Mage = 12.73 ± 0.43; 56.2% male) were assessed across three waves. Guided by the Functionalist Theory of Emotion and the Process Model of Emotion Regulation, we tested two parallel mediation models: one distinct predictive model for each outcome to examine domain-specific pathways, and one joint predictive model for both outcomes to assess potential cross-domain associations. RESULTS: In the distinct predictive model, sadness rumination mediated the relationship between harsh parenting and depressive symptoms, whereas anger rumination mediated the relationship between harsh parenting and reactive-proactive aggression. In the joint predictive model, sadness rumination emerged as a shared mediator of both outcomes. Gender differences revealed stronger depressive symptom-related pathways in males and greater reactive-proactive aggression in females.
Depression polygenic risk-linked multimodal MRI network and associated cognitive dysfunction.
Ma Y, Tao Y, Amos TJ … +4 more , Yan Y, Wang M, Liao Q, Yang X
J Affect Disord · 2026 Jun · PMID 42225244 · Publisher ↗
Major depressive disorder (MDD) involves complex genetic and neurobiological factors. This study integrated polygenic risk scores (PRS), neurocognitive assessments, and multimodal neuroimaging to examine relationships am...
Major depressive disorder (MDD) involves complex genetic and neurobiological factors. This study integrated polygenic risk scores (PRS), neurocognitive assessments, and multimodal neuroimaging to examine relationships among genetic liability, brain alterations, and cognitive performance in MDD. A total of 74 patients with MDD and 70 healthy controls (HCs) underwent cognitive testing and MRI scans, with gray matter volume (GMV) and amplitude of low-frequency fluctuations (ALFF) extracted as neuroimaging features. PRS were calculated using PRSice based on GWAS summary statistics of depression in East Asian populations, with quality control including MAF filtering, LD pruning, and removal of related individuals. Using multimodal canonical correlation analysis with reference combined with joint independent component analysis (MCCAR + jICA), we identified a PRS-related multimodal brain component involving occipital, frontal, parietal and temporal regions. The identified component exhibited significantly lower ALFF loadings, but not GMV loadings, suggesting greater sensitivity to functional than structural alterations in MDD compared with HCs. PRS scores were negatively associated with performance in pattern recognition memory tasks. These exploratory findings provide preliminary evidence linking genetic susceptibility, multimodal brain alterations, and cognitive dysfunction in MDD, and highlight the potential value of multimodal fusion approaches for investigating genetically informed brain-cognition pathways.
The impact of accelerated 40 Hz transcranial alternating current stimulation on sleep in patients with major depressive disorder: A secondary analysis of a randomized controlled trial.
Zhang Z, Liu Z, Ji Y … +13 more , Xu Y, Zheng C, Xu M, Wang Y, Ye X, Zhang Y, Zhang J, Li Y, Zhang Z, Zhou D, Yu H, Li X, Yu C
J Affect Disord · 2026 May · PMID 42217647 · Publisher ↗
BACKGROUND: Sleep disturbances are prevalent in major depressive disorder (MDD) and are associated with poor clinical outcomes and increased relapse risk. Current treatments often fail to adequately address comorbid slee...
BACKGROUND: Sleep disturbances are prevalent in major depressive disorder (MDD) and are associated with poor clinical outcomes and increased relapse risk. Current treatments often fail to adequately address comorbid sleep problems. Transcranial alternating current stimulation (tACS) at gamma frequency showed potential for modulating neural oscillations relevant to mood and sleep, but evidence in patients with MDD who have sleep disturbances remains limited. OBJECTIVE: This study aims to evaluate the efficacy and feasibility of an accelerated 40 Hz γ-tACS protocol targeting the bilateral dorsolateral prefrontal cortex (DLPFC) on sleep in patients with MDD. METHODS: In this secondary analysis, 36 participants in the active group and 34 in the sham group finished the intervention. Both groups received twice-daily stimulation for 2 weeks. The primary outcome was the total score of Pittsburgh Sleep Quality Index (PSQI) and the seven component scores. RESULTS: Compared with sham group, the active tACS group showed a significant reduction in PSQI total score from baseline to Week 2. Significant reductions were observed in several PSQI component scores, including subjective sleep quality, sleep efficiency, sleep disturbance, sleep medication use, and daytime dysfunction. In addition, insomnia factor scores extracted from the 24-item Hamilton Rating Scale for Depression (HAMD-24) showed greater reductions in the active group. CONCLUSIONS: The twice-daily 40 Hz γ-tACS protocol was well-tolerated and associated with significant improvements in sleep quality in patients with MDD. Considering its efficacy and shortened treatment schedule, accelerated γ-tACS may serve as a promising and efficient intervention for sleep disturbances in patients with MDD.
Treatment outcomes across subgroups of stroke survivors receiving psychological treatment for anxiety and depression.
Gallagher L, Saunders R, Buckman JEJ … +6 more , Bell V, El Baou C, Pilling S, John A, Stott J, Suh JW
J Affect Disord · 2026 May · PMID 42217646 · Publisher ↗
BACKGROUND: Stroke increases the risk of developing depression and anxiety. While psychological therapies are a recommended first-line treatment, outcomes vary between stroke survivors. Identifying those at risk of poore...
BACKGROUND: Stroke increases the risk of developing depression and anxiety. While psychological therapies are a recommended first-line treatment, outcomes vary between stroke survivors. Identifying those at risk of poorer treatment outcomes could improve treatment selection and patient outcomes. This study aimed to identify classes of stroke survivors based on stroke-related clinical characteristics and examine their psychological treatment outcomes. METHODS: NHS Talking Therapies for anxiety and depression (NHS TTad) data, linked to secondary care health records, were used to identify stroke survivors referred to TTad services across England from 2012 to 2019 (N = 6349). Latent class analysis was used to identify patient subgroups based on stroke type, time from stroke diagnosis to psychological treatment, presence of hemiplegia or paraplegia, and physical comorbidities. A distal categorical outcome approach was used to assess treatment across classes. Logistic regression models were used to examine outcomes by treatment intensity within each class. RESULTS: Four statistically distinct classes were identified, primarily differentiated by the type of stroke and time to access psychological treatment. Reliable recovery rates varied from 50 to 55% across classes, with deterioration rates ranging from 5 to 8%. High-intensity treatment was associated with reduced dropout rates in three classes. CONCLUSION: There were limited differences in psychological treatment outcomes between classes of stroke survivors. Stroke-related variables used in this study appear insufficient on their own to meaningfully stratify stroke survivors by psychological treatment prognosis. Future research should incorporate additional patient-level data, such as measures of cognition and language, to develop more clinically informative subgrouping.
Pubertal timing and tempo and depression risk in adolescent boys and girls: A Danish population-based cohort study.
Benson TE, Gaml-Sørensen A, Clemmensen PJ … +6 more , Thomsen AML, Torvik FA, Buyukkececi Z, Myrskylä M, Strandberg-Larsen K, Ramlau-Hansen CH
J Affect Disord · 2026 May · PMID 42217645 · Publisher ↗
PURPOSE: To investigate associations between pubertal timing and tempo and depressive symptoms and clinically diagnosed depression in adolescent boys and girls. METHODS: Data were obtained from the Danish National Birth...
PURPOSE: To investigate associations between pubertal timing and tempo and depressive symptoms and clinically diagnosed depression in adolescent boys and girls. METHODS: Data were obtained from the Danish National Birth Cohort (n = 15,818). Pubertal development was self-reported half-yearly from ages 11-18. Depressive symptoms at age 18 were assessed using the Major Depression Inventory, and clinically diagnosed depression was identified in the Danish National Patient Register. Pubertal timing and tempo were estimated using non-linear mixed-effects growth models. Associations with depressive symptoms were analysed using multinomial logistic regression, and associations with clinically diagnosed depression using binomial logistic regression. RESULTS: In girls, earlier and faster breast development were associated with higher risks of depressive symptoms (RRR = 1.11 (95% CI: 1.00-1.23) and 1.69 (95% CI: 1.08-2.64)), and earlier breast development and menarche were associated with clinically diagnosed depression (RR = 1.27 (95% CI: 1.00-1.60) and 1.36 (95% CI: 1.03-1.79)). In boys, earlier pubic hair development and voice break were associated with depressive symptoms (RRR = 1.32 (95% CI: 1.07-1.63) and 1.35 (95% CI: 1.11-1.63)), while earlier pubic hair development and first ejaculation were associated with clinically diagnosed depression (RR = 1.66 (95% CI: 1.10-2.50) and 1.51 (95% CI: 1.16-1.98)). CONCLUSIONS: Earlier pubertal timing was associated with depressive symptoms and clinically diagnosed depression in both boys and girls, while faster breast development was associated with depressive symptoms in girls. Overall, pubertal timing was more strongly associated with adolescent depression than pubertal tempo.
Pramipexole exposure and risk of incident gambling disorder in individuals with psychiatric disorders: A nationwide register-based cohort study.
Lindström S, Wolfschlag M, Håkansson A … +1 more , Berge J
J Affect Disord · 2026 May · PMID 42217644 · Publisher ↗
BACKGROUND: Pramipexole, a dopamine agonist, has demonstrated antidepressant efficacy as an augmentation strategy in unipolar and bipolar depression. However, dopaminergic treatments are associated with impulse control d...
BACKGROUND: Pramipexole, a dopamine agonist, has demonstrated antidepressant efficacy as an augmentation strategy in unipolar and bipolar depression. However, dopaminergic treatments are associated with impulse control disorders, including gambling disorder, and evidence regarding behavioural risks in psychiatric populations remains limited. METHODS: We conducted a nationwide register-based cohort study including individuals with psychiatric disorders who were prescribed pramipexole between 2006 and 2021. Cumulative pramipexole exposure was quantified longitudinally and analysed as a time-varying variable. The primary outcome was incident, clinically diagnosed gambling disorder identified in specialised healthcare registers. Associations were examined using Cox proportional hazards models, adjusting for relevant sociodemographic and clinical covariates. RESULTS: During follow-up, incident gambling disorder was rare but occurred disproportionately among individuals with higher cumulative pramipexole exposure. A clear dose-response relationship was observed, with progressively increasing risk across exposure categories. Individuals with bipolar disorder exhibited a particularly elevated risk compared with other psychiatric diagnostic groups. CONCLUSIONS: In this nationwide psychiatric cohort, cumulative exposure to pramipexole was associated with an increased risk of incident gambling disorder, with evidence of a dose-response relationship. Although the absolute risk of clinically diagnosed gambling disorder was low-likely reflecting substantial underdiagnosis-the clinical consequences of gambling disorder are considerable. These findings complement trial evidence by highlighting behavioural risks associated with long-term dopaminergic treatment in routine psychiatric care and underscore the importance of exposure-aware prescribing and systematic monitoring, particularly among individuals with bipolar disorder.
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