Journal Of Affective Disorders[JOURNAL]
Sun
200 papers
Latent class modeling of repetitive transcranial magnetic stimulation response trajectories in treatment-resistant depression.
Weissman CR, Cui B, Benster L … +5 more , Stapper N, Miron JP, Daskalakis ZJ, Appelbaum LG, Kohn JN
J Affect Disord · 2026 Jun · PMID 42341943 · Publisher ↗
Over 30% of patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is effective for TRD, yet there is substantial heterogeneity in...
Over 30% of patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is effective for TRD, yet there is substantial heterogeneity in treatment response. The ability to characterize distinct response trajectories could improve clinical decision-making and enhance early triaging of patients receiving acute rTMS treatment. We applied latent class mixture modeling (LCMM) to Patient Health Questionnaire-9 (PHQ-9) scores collected weekly during acute rTMS treatment in 308 patients with TRD treated at the UCSD Interventional Psychiatry Program. We also conducted a sensitivity analysis with baseline-adjusted PHQ-9 scores. LASSO-penalized multinomial logistic regression with nested cross-validation identified baseline clinical predictors of trajectory class membership. A three-class quadratic model best fit raw PHQ-9 trajectories: High Baseline, Minimal Improvement (HBMI); Moderate Baseline, Moderate Improvement (MBMI); and High Baseline, Large Improvement (HBLI). The HBLI group achieved the greatest symptom reduction (65.5%) and highest response rate (84%). Baseline-adjusted modeling yielded a 2-class solution (moderate vs. large improvement). Predictive modeling of raw PHQ-9 achieved strong multi-class discrimination (AUC = 0.82). History of suicidal ideation was associated with higher odds of HBMI class membership, while tobacco use and lack of previous suicide attempt was associated with HBLI membership. In conclusion, patients with high baseline depression severity and suicidal ideation are at greatest risk for nonresponse and may benefit from early consideration of alternative interventions.
Longitudinal course of repetitive adolescent non-suicidal self-injury: Psychological functioning among adults who have ceased or continued to self-injure.
Claréus B, Daukantaitė D
J Affect Disord · 2026 Jun · PMID 42341942 · Publisher ↗
Non-suicidal self-injury (NSSI) often emerges in adolescence, but the lack of longitudinal research means it remains unclear whether the risk of poor outcomes in adulthood reflects NSSI engagement specifically or broader...
Non-suicidal self-injury (NSSI) often emerges in adolescence, but the lack of longitudinal research means it remains unclear whether the risk of poor outcomes in adulthood reflects NSSI engagement specifically or broader adolescent vulnerabilities, and what predicts NSSI cessation among adults. This study addresses these gaps using data from a Swedish school cohort collected in 2007-2008 (N = 506-522, M = 13.7-14.7), 2017 (N = 375, M = 25.3), and 2023 (N = 252, M = 29.8). Participants were grouped as having reported repetitive NSSI in adolescence (≥5 instances in 2007/2008), and as having ceased (0 instances) or continued (≥1 instance) NSSI by 2017/2023, or as having never reported any NSSI. Both NSSI cessation and NSSI continuation were associated with poorer outcomes than never having reported NSSI. However, for the cessation group, all differences except self-views were explained by adolescent mental health. Relative to continued NSSI, cessation was associated with higher flourishing and lower depression, stress, emotion dysregulation, and self-hatred (∆EMM = 0.43-1.00, p = 0.017), independent of adolescent mental health. Continuation between ages 25 and 30 was predicted by lower flourishing (OR = 0.46, p = 0.018) and higher emotion dysregulation, self-inadequacy, and self-hatred (OR = 1.93-2.27, p ≤ 0.037). In conclusion, NSSI cessation by adulthood indicates improvement over continued engagement, although earlier experiences continue to influence adult psychological health. Improved emotion regulation, reduced self-criticism, and greater flourishing appear to be barriers to continuation and key targets for prevention and intervention among individuals with lived experience.
Maternal inflammation and oxidative stress during pregnancy and emotional-behavioral problems in children aged 1.5-3 years: A longitudinal repeated-measures study.
Park S, Woodbury ML, Hao W … +9 more , Park SK, Mukherjee B, Huerta-Montañez G, Rosario-Pabón Z, Vélez-Vega CM, Cordero JF, Alshawabkeh A, Watkins DJ, Meeker JD
J Affect Disord · 2026 Jun · PMID 42336328 · Publisher ↗
Emotional and behavioral problems (EBP) in early childhood have been associated with enduring mental health problems as well as with poor academic outcomes later in life. Thus, understanding the pathology and risk factor...
Emotional and behavioral problems (EBP) in early childhood have been associated with enduring mental health problems as well as with poor academic outcomes later in life. Thus, understanding the pathology and risk factors is essential for developing effective preventive strategies. While recent experimental studies suggest the linkage between maternal inflammation and oxidative stress during pregnancy and offspring's EBP symptoms, few epidemiological studies have explored both simultaneously. In this study, maternal inflammation biomarkers were measured at 18 and 26 weeks of gestation, and oxidative stress biomarkers were measured at 18, 22, and 26 weeks of gestation. Child EBP were assessed at 18 months, 2 years, and 3 years of age using the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5). We investigated the associations of maternal inflammation and oxidative stress biomarkers during pregnancy with child EBP. We additionally explored effect modification by the timing of measurement during pregnancy, child sex, and age. Higher concentrations of inflammatory and oxidative stress biomarkers were associated with higher CBCL/1.5-5 scores, indicating presence of more problematic symptoms. Inflammatory biomarker associations were stronger among boys, while oxidative stress associations varied by gestational timing and were strongest later in pregnancy. Our findings suggest that maternal inflammation and oxidative stress may contribute to EBP outcomes in early childhood, with potential windows of susceptibility during pregnancy and differential vulnerability by child sex.
Altered perivascular water diffusivity links childhood trauma and major depressive disorder: A multimodal integration of cognition, neuroimaging, and transcriptomics.
Wang M, Yan Y, Dou Y … +5 more , Wei J, Zhao L, Ni R, Yang X, Ma X
J Affect Disord · 2026 Jun · PMID 42336327 · Publisher ↗
AIMS: Perivascular water diffusivity, as assessed by diffusion tensor imaging along the perivascular space (DTI-ALPS) index, serves as an indirect imaging marker potentially reflecting glymphatic function. This study inv...
AIMS: Perivascular water diffusivity, as assessed by diffusion tensor imaging along the perivascular space (DTI-ALPS) index, serves as an indirect imaging marker potentially reflecting glymphatic function. This study investigated its associations with childhood trauma and major depressive disorder (MDD) and explored the related biological mechanisms. METHODS: We enrolled 86 patients with MDD and 74 matched healthy controls (HCs). Childhood trauma, cognitive performance, and peripheral blood transcriptomic profiles were evaluated. Regression and exploratory mediation analyses were performed. RESULTS: MDD patients exhibited lower DTI-ALPS index (F = 15.716, p < 0.001), and poor attention, processing speed, visual memory and executive function performance (q < 0.05) than HCs. In the MDD group, the DTI-ALPS index was negatively correlated with CTQ score (r = -0.251, p = 0.02), spatial working memory strategy (SWM_Stra; r = -0.272, p = 0.013) and rapid visual information processing mean latency (RVP_ML; r = -0.232, p = 0.036). The yellow, turquoise, and blue transcriptomic modules were associated with MDD and enriched in immune-inflammatory, intracellular trafficking, and mitochondrial metabolic pathways, whereas the magenta module was associated with the DTI-ALPS index (r = -0.25, p = 0.022) and enriched in hemostasis, platelet activation, and vascular integrity pathway. Mediation analyses revealed that the DTI-ALPS index partially mediated the relationships between childhood trauma and the diagnosis of MDD (indirect effect: coefficient = 0.0001, p = 0.0372). CONCLUSIONS: Altered DTI-ALPS may reflect links between childhood trauma, cognitive dysfunction, and vascular integrity, but as an indirect glymphatic marker, these findings require cautious interpretation.
Clinical and genetic association of comorbid provisional PMDD and ADHD in female patients with bipolar disorder.
Baek JH, Choi MJ, Shin Y … +8 more , Cho EY, Choi Y, Lee H, Myung W, Ha TH, Ahn YM, Ha K, Hong KS
J Affect Disord · 2026 Jun · PMID 42336326 · Publisher ↗
BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a common comorbidity in bipolar disorder (BD), and its association with severe illness course and other comorbidity in BD has been reported. AIMS & OBJECTIVES: This s...
BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a common comorbidity in bipolar disorder (BD), and its association with severe illness course and other comorbidity in BD has been reported. AIMS & OBJECTIVES: This study aims to investigate clinical characteristics and polygenic risk features of the subgroup with DSM-5-based provisional PMDD in BD. Attention deficit/hyperactivity disorder (ADHD) symptoms and polygenic risk of ADHD were included in the analysis based on recent evidence suggesting the clinical and polygenic association between PMDD and ADHD in non-bipolar populations. METHODS: Female patients with BD were grouped into 'with PMDD' and 'without PMDD.' Clinical characteristics, including other comorbidities, and polygenic risk score (PRS) of major psychiatric disorders were compared between the two groups. RESULTS: Of the 423 participants, 187 (44.2%) met the DSM-5 criteria for provisional PMDD. Those with PMDD were more likely to have bipolar II disorder, had earlier illness onset, and experienced more frequent major depressive episodes. The prevalence of comorbid bulimia nervosa and ADHD symptom scores was higher in the PMDD group, compared to those without PMDD. In the analysis of genetic correlation using PRS for 5 major psychiatric disorders, the polygenic risk of ADHD was significantly associated with the severity of both PMDD symptom severity and ADHD symptoms. DISCUSSION & CONCLUSION: Our findings indicate a clinical and genetic association between comorbid PMDD and ADHD symptoms in BD. It is suggested that pleiotropic expression of a common genetic vulnerability might constitute a unique subgroup of BD, characterized by multiple comorbidities with underlying mood dysregulation.
Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar depression: A systematic review and dose-related network meta-analysis across different age groups.
Fornaro M, Di Lorenzo C, Oliva V … +2 more , De Prisco M, Vieta E
J Affect Disord · 2026 Jun · PMID 42331044 · Publisher ↗
BACKGROUND: Acute bipolar depression poses a significant burden and socioeconomic costs. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar depression, cons...
BACKGROUND: Acute bipolar depression poses a significant burden and socioeconomic costs. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar depression, considering dose effects across different age groups. METHODS: We conducted a network meta-analysis (NMA), searching for randomized controlled trials (RCTs) comparing pharmacological interventions against each other/or placebo in patients with acute bipolar depression (Type-I/Type-II/other), indexed in PubMed/MEDLINE, Embase, Web-of-Science/and Scopus (database inception up to 2025.11.25). Co-primary outcomes were change in depressive symptoms/response/and acceptability. Tolerability/remission/change in anxious symptoms/and risk-of-manic/hypomanic switches were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. RESULTS: 103 RCTs, encompassing 71 distinct treatment combinations, included 20,941 participants. Sensitivity analysis including low-risk-of-bias studies only and excluding outliers for possible effect modifiers indicated that lamotrigine 50 mg/day or 200 mg/day, quetiapine extended-release 150 mg/day and 300 mg/day, and lumateperone 42 mg/day outperformed placebo for depressive symptoms, with estimates ranging from -1.53(95%C.I. = -2.13;-0.93) for lamotrigine 50 mg/day, to -0.36(95%C.I. = -0.68;-0.04) for lumateperone 42 mg/day. Several additional drugs might be efficacious, although they emerged as outliers for either mean age of participants/proportion of females/BD-II participants/psychotic features/rapid cycling/baseline severity of depression/and trial duration. No treatment outperformed placebo for response/remission/acceptability/tolerability/and manic/hypomanic switches. CONCLUSIONS: Our findings are consistent with previous NMAs and current guidelines, thereby expanding knowledge by concurrently appraising different drugs, doses, and age groups.
Temporal associations of suicidal ideation within perinatal depressive symptom networks: A cross-lagged network analysis of over 90,000 Chinese women.
Wu D, Kong Y, Zhou R … +6 more , Gao Y, Liu J, Lin Q, Zhang J, Jin S, Chen Y
J Affect Disord · 2026 Jun · PMID 42331043 · Publisher ↗
BACKGROUND: Maternal suicide is a leading cause of postpartum death. Suicidal ideation in perinatal depression is associated with significant risks to maternal, infant, and family well-being. While previous studies have...
BACKGROUND: Maternal suicide is a leading cause of postpartum death. Suicidal ideation in perinatal depression is associated with significant risks to maternal, infant, and family well-being. While previous studies have explored trajectories of perinatal suicidal ideation, the dynamic relationships between symptoms remain unclear. OBJECTIVE: To examine the predictive role of suicidal ideation within the perinatal depression symptom network across different stages of the perinatal period, using cross-lagged network analysis. METHODS: Data were obtained from a population-based perinatal depression screening program in Shenzhen, China (June 2020-May 2022). Among 144,887 women with at least one EPDS screening record, 91,123 contributed data from at least two survey time points; after excluding 694 women who delivered before 32 gestational weeks, 90,429 were included in the final analysis. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Cross-lagged networks were estimated using the 'glmnet' and 'qgraph' packages in R, with missing data imputed via the mice package. RESULTS: Suicidal ideation (EPDS Item 10) demonstrated the strongest predictive influence (out-expected influence) across all three cross-lagged networks. In the T3 → T4 network (late pregnancy to postpartum), suicidal ideation showed the highest out-expected influence (0.193), predicting symptoms including sadness (E8), tearfulness (E9), guilt (E3), and sleep disturbance (E7). The strongest edge across all networks was between suicidal ideation and sadness, with edge weights ranging from 0.1164 to 0.1820. Stability analyses indicated high robustness (CS-coefficients >0.75). CONCLUSION: Suicidal ideation plays a central and sustained predictive role in the evolution of perinatal depressive symptoms, particularly from late pregnancy to postpartum. Systematic monitoring of suicidal ideation and targeted interventions across perinatal stages are essential to mitigate the progression of depressive symptoms. REGISTRATION: Not registered.
Shifts in the brain sex continuum in major depressive disorder: Evidence for a persistent neurobiological marker.
Chen Y, Zhu L, Zhang Y … +8 more , Li J, Langley C, Sahakian BJ, Feng J, Wang X, Si T, Luo Q, ZIB Consortium
J Affect Disord · 2026 Jun · PMID 42331042 · Publisher ↗
BACKGROUND: Major depressive disorder (MDD) heterogeneity impedes the discovery of robust neurobiological markers. This study investigated the brain sex continuum (BSC) score, which is a system-level functional architect...
BACKGROUND: Major depressive disorder (MDD) heterogeneity impedes the discovery of robust neurobiological markers. This study investigated the brain sex continuum (BSC) score, which is a system-level functional architecture marker reflecting psychological androgyny (Zhang et al., 2021), as a persistent neurobiological alteration and replicable diagnostic marker in MDD and its association with symptoms and treatment. METHODS: Resting-state functional connectivity (rsFC) was analyzed in two independent longitudinal cohorts of unmedicated MDD patients (Xiangya Hospital, XYH: n = 173 and Peking University, PKU: n = 79) and healthy controls (n = 238 and 89, respectively). We confirmed the applicability of the BSC score in current samples. Group differences, effects of 8-week antidepressant treatment, and associations with depressive symptoms (17-item Hamilton depression rating scale, HAMD-17) were evaluated. RESULTS: No single individual rsFC consistently differentiated MDD patients from controls across both cohorts. However, BSC scores were reproducibly elevated in unmedicated MDD patients versus controls (PKU: Odds Ratio,OR=7.69,95%CI,0.08to34.45, and XYH: OR=2.39,95%CI,0.99to5.81), indicating a shift toward the extreme male end of the continuum. This BSC shift was primarily driven by elevated alterations in between-network connectivity, particularly in female patients. Crucially, this shift persisted post-treatment in both cohorts and substantially improved diagnostic accuracy. Strikingly, BSC scores showed no significant association with baseline HAMD or symptom changes post-treatment. CONCLUSIONS: The BSC represents a persistent neurobiological marker in MDD that is dissociated from clinical symptom expression. This uncoupling reveals a core neuropathology distinct from symptom-based diagnostic frameworks, advancing biomarker development for heterogeneous depression.
Racial, ethnic, and nativity disparities in elevated symptoms and diagnosis of perinatal mood and anxiety disorders: A population-level study.
Rokicki S, Fink ED, Blumenfeld J
J Affect Disord · 2026 Jun · PMID 42331041 · Publisher ↗
BACKGROUND: This study evaluated racial, ethnic, and nativity disparities in diagnosis of perinatal mood and anxiety disorders (PMADs) for individuals with elevated symptoms in a state with universal screening of perinat...
BACKGROUND: This study evaluated racial, ethnic, and nativity disparities in diagnosis of perinatal mood and anxiety disorders (PMADs) for individuals with elevated symptoms in a state with universal screening of perinatal depression. METHODS: This was a cross-sectional analysis of linked New Jersey birth records and hospital discharge records between January 2016 and December 2019 (n = 338,537 births). Primary outcomes were a positive screen for elevated symptoms using the Edinburgh Postnatal Depression Scale (EPDS ≥ 10) and positive EPDS with a PMAD diagnosis on the delivery hospitalization discharge record. Logistic regression was used to estimate associations between racial, ethnic, and nativity groups and outcomes. We also examined associations between screening and diagnosis outcomes at delivery and postpartum use emergency department (ED) use. RESULTS: Compared with White US-born, births to Asian/Pacific Islander foreign-born mothers had significantly higher odds of positive EPDS (adjusted OR 1.84, 95%CI 1.73-1.96), but lower odds of positive EPDS with PMAD diagnosis (AOR 0.36 95%CI 0.29-0.45). Similar differences were found for Black US-born, Black foreign-born, Hispanic US-born, and White foreign-born births. Compared to those with a negative screen, a positive screen without a diagnosis was associated with higher odds of a psychiatric ED visit in the first year postpartum (AOR 2.23, 95%CI 1.99-2.51). CONCLUSION: This population-level study found that in a setting with universal screening of perinatal depression, there remain substantial racial and ethnic disparities in the pathway from screening to diagnosis. Further research is needed to understand the mechanisms behind these findings and identify policies to improve equity in perinatal mental health care.
Cyberbullying victimization and adolescent emotional and conduct problems: Roles of loneliness, emotion dysregulation, and self-esteem.
Li Y, Knoll M, Obsuth I
J Affect Disord · 2026 Jun · PMID 42331040 · Publisher ↗
Cyberbullying victimization (CV) is a significant stressor linked to youth mental health outcomes, including both emotional and conduct problems. While previous studies have identified various mediators including affecti...
Cyberbullying victimization (CV) is a significant stressor linked to youth mental health outcomes, including both emotional and conduct problems. While previous studies have identified various mediators including affective, cognitive, and social domains, few studies have simultaneously examined them within an integrated model in a longitudinal design. This study investigates whether loneliness, emotion dysregulation, and self-esteem mediate the association between CV and later emotional and conduct problems. A total of 501 Chinese adolescents aged between 15 and 18 years old (53.3% female; M age = 16.33, SD = 0.47) participated in a two-wave longitudinal study with a 6-month interval. Structural equation modeling was used to test mediation effects, controlling for gender and age. Results revealed that CV at Time 1 (T1) was prospectively associated with higher emotional and conduct problems at Time 2 (T2). Loneliness and emotion dysregulation at T2 were significant mediators of CV and both emotional and conduct problems, whereas self-esteem at T2 was not a significant mediator for both outcomes. Subscale analyses of emotion dysregulation revealed distinct emotion-cognitive patterns across outcomes. Limited access to effective emotion-regulation strategies primarily explained the association between CV and emotional problems, whereas impulse-control difficulties most strongly accounted for the link between CV and conduct problems. Interventions should be multi-component, targeting these shared and distinct psychological factors through strategies addressing social isolation and emotion regulation skills while also incorporating outcome-specific approaches for comprehensive prevention and treatment.
Associations between psychiatric diagnoses, comorbidity, and psychological pain across suicide-related presentations: A comparative study in clinical populations.
Aschenbrenner LM, Baumgartner A, Sedlinská MA … +4 more , Frei A, Walther S, Adorjan K, Gysin-Maillart A
J Affect Disord · 2026 Jun · PMID 42323989 · Publisher ↗
OBJECTIVE: Suicidal ideation and behaviour (SIB) occur across various psychiatric disorders. Although certain disorders are associated with elevated rates of SIB, diagnostic labels alone provide limited information about...
OBJECTIVE: Suicidal ideation and behaviour (SIB) occur across various psychiatric disorders. Although certain disorders are associated with elevated rates of SIB, diagnostic labels alone provide limited information about suicide-related presentations. Psychological pain has been proposed as an important experiential process operating across diagnostic boundaries, but its relationship with psychiatric comorbidity remains poorly understood. This study examined associations between psychiatric diagnoses, the number of co-occurring diagnoses, and psychological pain across clinical groups differing in suicide-related presentations. METHOD: N = 233 psychiatric inpatients were recruited (recent suicide attempters [SUAT], recent suicide ideators [SUID], clinical controls [CLIN]). Psychiatric diagnoses were assessed using the Mini-International Neuropsychiatric Interview; psychological pain was measured using the Mee-Bunney Psychological Pain Assessment Scale. Analyses evaluated group differences in the number of diagnoses and psychological pain, their association, and diagnostic patterns. RESULTS: SUAT and SUID had higher mean numbers of diagnoses than CLIN; these did not differ between SUAT and SUID. Psychological pain differed across all groups and was positively associated with the number of diagnoses across the sample and within each group. Affective-anxiety and alcohol-dysthymic profiles were associated with suicide-related status. CONCLUSION: The number of diagnoses did not reflect differences between suicide-related groups. Although suicidal groups displayed greater diagnostic complexity than non-suicidal controls, differences between ideation and attempt were not mirrored by the number of diagnoses. Psychological pain differentiated all groups and was associated with the number of diagnoses. These findings suggest that psychological pain captures aspects of suicide-related clinical states not fully represented by diagnostic descriptions alone.
Differentiating suicidal thoughts, plans, and attempts in U.S. military veterans.
Fischer IC, Nichter B, Hill ML … +3 more , Na PJ, O'Connor RC, Pietrzak RH
J Affect Disord · 2026 Jun · PMID 42323988 · Publisher ↗
BACKGROUND: Although numerous risk and protective factors have been identified as correlates of suicidal thoughts and behaviors (STBs), less is known about factors that differentiate increasing levels of suicide risk, fr...
BACKGROUND: Although numerous risk and protective factors have been identified as correlates of suicidal thoughts and behaviors (STBs), less is known about factors that differentiate increasing levels of suicide risk, from suicidal ideation (SI) to suicide planning (SP) to suicide attempts (SA). This study examined the prevalence and correlates of these STB stages in a nationally representative sample of U.S. veterans. METHODS: Data were analyzed from the 2025-2026 National Health and Resilience in Veterans Study (NHRVS; N = 2636). Weighted estimates were used to determine the lifetime prevalence of SI, SP, and SA. Multivariable binary logistic regression analyses examined sociodemographic, military, psychiatric, and clinical characteristics associated with (1) SI vs. no lifetime history of STBs, (2) SP vs. SI, (3) SA vs. SI, and (4) SA vs. SP. RESULTS: The prevalences of SI, SP, and SA were 18.9%, 8.1%, and 5.0%, respectively. In multivariable analyses, SI (vs. no STB history) was associated with younger age, greater adverse childhood experiences (ACEs) and cumulative trauma burden, higher self-criticism, lower meaning in life, lifetime non-suicidal self-injury (NSSI), and major depressive disorder (MDD). Relative to SI, SP was associated with age, identifying as Non-Hispanic Black, being widowed, divorced, or separated, NSSI, and MDD, and posttraumatic stress disorder. Relative to SI, SA was associated with greater ACEs, NSSI, and anxiety disorder, while SA (vs. SP) was associated with greater ACEs, anxiety disorder, being unpartnered, and identifying as biracial/multiracial. CONCLUSIONS: Findings broadly support ideation-to-action theories and suggest suicidal thoughts and suicidal behavior in U.S. veterans may be influenced by overlapping but distinct processes. They also underscore the importance of addressing both distal vulnerability processes and proximal behavioral risk factors across stages of STBs to inform more precise and stage-specific suicide prevention strategies.
Investigating the effects of antidepressants on measures of insulin resistance in major depressive disorder: A systematic review.
Wong S, Le GH, Zheng YJ … +4 more , Guillen-Burgos HF, Dri CE, Teopiz K, McIntyre RS
J Affect Disord · 2026 Jun · PMID 42323987 · Publisher ↗
BACKGROUND: Persons with depression are disproportionately at risk for developing insulin resistance. Replicated evidence indicates that insulin resistance blunts acute antidepressant response; however, some antidepressa...
BACKGROUND: Persons with depression are disproportionately at risk for developing insulin resistance. Replicated evidence indicates that insulin resistance blunts acute antidepressant response; however, some antidepressants exacerbate insulin resistance risk. Herein, we aim to comprehensively evaluate previous literature reporting on the effects of antidepressants on measures of insulin resistance with the view to disaggregate class- and drug-specific effects. METHODS: A systematic search on PubMed, Ovid and Scopus (inception-July 2025) was conducted, with a manual search of Google Scholar and reference lists. Two reviewers (S.W. and G.H.L.) independently screened studies. Clinical trials investigating FDA-approved antidepressants on a validated measure of insulin resistance were included. Studies were assessed using the National Institute of Health quality assessment tools. RESULTS: Select tricyclic antidepressants (i.e., nortriptyline, amitriptyline, imipramine) were associated with acute and long-term disruptions in insulin sensitivity. SSRIs were not associated with acute alterations in insulin sensitivity. Preliminary evidence suggests agomelatine and bupropion are metabolically neutral and may improve insulin resistance in persons with diabetes mellitus. SNRIs do not adversely affect glucose-insulin signaling in the long-term. There was a paucity of studies reporting the effects of other antidepressant classes and agents. CONCLUSION: The effect of antidepressants on mechanisms mediating insulin sensitivity is mixed, with a relatively limited body of evidence currently available. While select SSRIs and tricyclic antidepressants may adversely affect glucose-insulin homeostasis, conclusions remain preliminary. The development of novel antidepressants may provide an opportunity to optimize psychiatric and metabolic outcomes. Identifying mechanisms contributing to insulin resistance could inform future discovery and development of antidepressants.
Risk factors and help-seeking behavior for postpartum depression following Edinburgh postnatal depression scale screening: A retrospective study of 586 patients.
Atak Z, Rahimli Ocakoğlu S, Ocakoğlu G … +3 more , Uyaniklar ÖÖ, Öye E, Küçüktüfekçi AH
J Affect Disord · 2026 Jun · PMID 42323986 · Publisher ↗
Postpartum depression is a significant mental health condition that may lead to severe consequences, including suicidal ideation. This study aimed to determine the risk groups, and help-seeking behavior among postpartum...
Postpartum depression is a significant mental health condition that may lead to severe consequences, including suicidal ideation. This study aimed to determine the risk groups, and help-seeking behavior among postpartum women screened using the Edinburgh Postnatal Depression Scale (EPDS). This retrospective study included 586 postpartum women. EPDS scores were categorized as ≤9 (low risk), 10-12 (mild risk), and ≥13 (high risk). Demographic and obstetric data, including delivery characteristics and neonatal outcomes, were analyzed. Ordinal logistic regression was used to identify factors associated with higher depression scores. The incidence of high-risk postpartum depression was found to be 8.36% (n = 49/586). Regarding help-seeking behavior, while all patients scoring 10 or higher on the EPDS were formally referred for psychiatric evaluation, the subsequent clinical admission rate to the psychiatric outpatient clinic was only 13.7%. The proportion of preterm births was higher in the high-score group (≥13) compared with the low-score group (≤9) (32.7% vs 18.1%, respectively), demonstrating a marginally significant association (p = 0.050, Cramer's V = 0.10). The 5-minute Apgar score was inversely associated with higher depression scores (OR = 0.87, 95% CI: 0.77-0.99, p = 0.031). Cesarean and assisted vaginal deliveries showed a tendency toward increased risk, although these associations were not statistically significant. Despite screening, help-seeking behavior among at-risk women remained markedly low, highlighting a critical gap between identification and access to care. Targeted screening of high-risk groups, particularly women with preterm birth or adverse neonatal outcomes, may improve early detection and intervention.
Corrigendum to "a healthy lifestyle is associated with lower risk of depression in type 2 diabetes, irrespective of genetic susceptibility: A UK biobank cohort study" [J. Affect. Disord. 405 (2026) 121657, doi:10.1016/j.jad.2026.121657].
Zhang Y, Zhao P, Lou H … +5 more , Zhang W, Zhang C, Liao J, Zhou H, Sun H
J Affect Disord · 2026 Jun · PMID 42323215 · Publisher ↗
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Network-based assessment of plasticity predicts vulnerability to depressive symptomatology in healthy individuals.
Delli Colli C, Viglione A, Poggini S … +1 more , Branchi I
J Affect Disord · 2026 Jun · PMID 42322981 · Publisher ↗
Early identification of individuals at elevated risk for depressive symptoms is essential for prevention. Plasticity, defined as the capacity to transition across mental states, may serve as an individual prognostic mark...
Early identification of individuals at elevated risk for depressive symptoms is essential for prevention. Plasticity, defined as the capacity to transition across mental states, may serve as an individual prognostic marker of mental health trajectories. Indeed, plasticity should be understood from a for-better-or-for-worse perspective, as it enables changes not only toward improvement, such as recovery, but also toward worsening, determining vulnerability. Recently, a network theory of plasticity has been introduced, proposing a computational, network-based approach to quantify plasticity and thus the individual's capacity for change, by estimating connectivity strength among psychological features. Using such an approach, we analyzed ecological momentary assessment (EMA) and symptomatology data collected in 146 healthy people from the Multi-Mood study to test whether baseline plasticity predicts vulnerability to depressive symptomatology. Baseline plasticity was operationalized as the inverse of connectivity strength within EMA items, so that high plasticity corresponds to weak connectivity. We found that individual connectivity strength at baseline was negatively associated with maximal absolute subsequent change in depressive symptoms (ρ = -0.54, P < .001). Additionally, individuals with strong connectivity reached depressive-symptom threshold later (χ = 41, P < .0001) and showed a markedly reduced risk (HR = 0.20, P < .001) compared with those with weak connectivity. These findings support the network-based assessment of plasticity as a prognostic marker for early detection and prevention strategies within precision psychiatry.
Corrigendum to "Depression severity as a predictor of cardiovascular-kidney-metabolic syndrome progression and mortality: Results from two nationally representative cohort studies" [J. Affect. Disord. 388 (2025) 119606].
He Y, Lan L, Liu Y … +3 more , Liang Y, Hu N, Zhang X
J Affect Disord · 2026 Jun · PMID 42321048 · Publisher ↗
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Variation in sleep and instability in mood in patients with bipolar disorder and the association between these - an exploratory post hoc study on daily smartphone-based data from two separate randomised controlled trials.
Faurholt-Jepsen M, Risom A, Bruun CF … +3 more , Budtz-Jørgensen E, Vinberg M, Kessing LV
J Affect Disord · 2026 Jun · PMID 42320790 · Publisher ↗
BACKGROUND: Dysregulation in circadian rhythms, including sleep abnormalities, is a central feature in bipolar disorder during all illness phases. This exploratory post hoc study investigated the association between vari...
BACKGROUND: Dysregulation in circadian rhythms, including sleep abnormalities, is a central feature in bipolar disorder during all illness phases. This exploratory post hoc study investigated the association between variation in sleep and instability in mood based on day-to-day patient-reported smartphone-based data in patients with bipolar disorder. METHODS: Data from patients with bipolar disorder from two prior studies (A-Bipolar and SMART-Bipolar) were included for exploratory analyses. Patients provided daily smartphone-based evaluations of sleep and mood. A total of 370 patients with bipolar disorder each providing data for six months were included in the analyses. We analysed how various summaries of sleep variation were associated with mood instability, using linear mixed effect regression models. RESULTS: There was a positive association between variation in sleep for both the prior three days (1.22, 95%CI: (1.19; 1.24), p < 0.0001) as well as the prior week (1.40,95% CI: (1.36, 1.44), p < 0.0001)) and mood instability. Interestingly, increasing sleep up to a certain point around eight hours was associated with decreased mood instability. Increasing sleep after this point was associated with increased mood instability. The estimated inflection point for this choice of knots was 8.05 h (95% CI: 7.20,8.90) for the A-bipolar study and 8.24 h (95% CI: 6.24,10.24) for SMART-Bipolar study. LIMITATIONS: Analyses were exploratory and post hoc. Sleep and mood were patient-reported. Findings should be interpreted with caution. Temporal ordering of the associations cannot be concluded. CONCLUSION: In this exploratory study of patients with bipolar disorder, short-term fluctuations in sleep were significantly associated with increased mood instability, highlighting the dynamic interplay between circadian regulation and affective variability.
Proximal contributors to suicide risk in college students: A multidimensional ecological momentary assessment.
Dell'Acqua C, Mastromatteo LY, Degasperi G … +6 more , Cellini N, Soliman L, Oppioli L, Palomba D, Scrimin S, Messerotti Benvenuti S
J Affect Disord · 2026 Jun · PMID 42320789 · Publisher ↗
Given the increasing prevalence of suicide risk among young adults, identifying proximal risk factors remains a key challenge. Traditional approaches focusing on distal predictors provide limited insight into short-term...
Given the increasing prevalence of suicide risk among young adults, identifying proximal risk factors remains a key challenge. Traditional approaches focusing on distal predictors provide limited insight into short-term fluctuations in risk. The present study examined whether daily variations in sleep, physical activity, and physiological arousal, in interaction with positive and negative life events, were associated with short-term changes in suicide risk. A sample of 104 university students completed an 8-day ecological momentary assessment protocol with four daily prompts assessing suicide risk and affect. Sleep and physical activity were continuously monitored via wrist actigraphy, and heart rate was assessed using a wearable device. Linear mixed-effects models were used to examine within- and between-person associations between total sleep time, daytime acceleration, and heart rate and next-day suicide risk, as well as their interactions with daily positive and negative life events. Within-person decreases in total sleep time and increases in heart rate predicted higher next-day suicide risk. Within-person increases in daytime acceleration were also associated with higher next-day suicide risk, although this effect was weaker in robust sensitivity analyses and should be interpreted cautiously. Daily negative life events moderated the associations between both physical activity and heart rate and suicide risk, such that these relationships were stronger on days characterized by higher levels of negative events. In contrast, positive life events showed limited buffering effects. These findings suggest that suicide risk in university students is linked to day-to-day changes in sleep, physical activity, and physiological arousal, especially in the presence of daily stressors.
Lifetime comorbid substance misuse in patients newly diagnosed with bipolar disorder.
Stanislaus S, Thirstrup CF, Kjærstad HL … +7 more , Sletved KSO, Faurholt-Jepsen M, Munkholm K, Miskowiak KW, Vinberg M, Coello K, Kessing LV
J Affect Disord · 2026 Jun · PMID 42320788 · Publisher ↗
BACKGROUND: Comorbid substance use is common in patients with bipolar disorder (BD) and associated with a more severe illness course and higher mortality rates. We aimed to investigate 1) the prevalence of lifetime comor...
BACKGROUND: Comorbid substance use is common in patients with bipolar disorder (BD) and associated with a more severe illness course and higher mortality rates. We aimed to investigate 1) the prevalence of lifetime comorbid substance misuse in patients with newly diagnosed BD compared with healthy controls (HC), and 2) differences in illness characteristics between patients with and without comorbid substance misuse. METHODS: We included 376 patients with newly diagnosed BD and 200 HC. Lifetime substance misuse (including alcohol and drug use) was identified through baseline interview and through systematic review of electronic health records. RESULTS: The prevalence of lifetime substance misuse was higher for patients with newly diagnosed BD (43%). Patients with BD had a high prevalence of lifetime comorbid drug misuse (38%) than alcohol misuse (19%). Among patients, lifetime substance misuse was associated with male sex (OR = 2.86 [1.82; 4.55] p < 0.001), childhood trauma (β = 5.33 [2.68; 7.99], p = 0.003), BD type I (OR = 1.71 [1.09; 2.68], p = 0.042), presence of suicide attempts (OR = 2.26 [1.36; 3.75], p = 0.005) and more sick days the preceding year (β = 41.43 [16.90; 65.96], p = 0.012). LIMITATIONS: Information regarding substance use was partly gathered retrospectively using electronic health records. HC were recruited among blood donors and may not be representative of the general population. CONCLUSION: We found a high prevalence of lifetime comorbid substance misuse, particularly drug misuse in patients with newly diagnosed BD. Lower clinical focus on drug use than alcohol may have contributed to higher observed prevalence of drug use. This highlights the need for early clinical assessment and integrated treatment.
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