BACKGROUND: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders among adolescents, significantly impairing psychosocial functioning. Early functional changes in adolescents with first-diagn...BACKGROUND: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders among adolescents, significantly impairing psychosocial functioning. Early functional changes in adolescents with first-diagnosis MDD are poorly understood. METHODS: This prospective cohort study utilized data from the sBEAD cohort between 2020 and 2024, comprising 274 adolescents with first-diagnosis MDD. Participants were evaluated psychosocial functioning based on Children's Global Assessment Scale scores with assessments at baseline, 4 weeks, 8 weeks, 3 months, and 12 months. Growth mixture models were applied to identify distinct trajectories of psychosocial functioning. Demographic and clinical data were collected, including household income, academic performance, age at illness onset, psychotic symptoms, and anxiety levels. A multinomial logistic regression model was used to identify factors significantly associated with functional trajectory membership. RESULTS: Four distinct functional trajectories were identified including persistent impairment (19.7%), early improvement with decline (30.7%), gradual improvement (33.9%), and sustained good functioning (15.7%). Baseline key factors influencing trajectory membership included household income, academic performance, years of education, psychic anxiety, and psychotic symptoms. Higher education and better academic performance were linked to more favorable trajectories, whereas higher anxiety scores and psychotic symptoms were associated with poor outcomes. CONCLUSION: This study identified heterogeneous functional trajectories among adolescents with first-diagnosis MDD and associated factors. The findings highlight the importance of early identification and targeted interventions for adolescents at risk of persistent functional impairment. Future research should focus on integrating biological markers and expanding follow-up duration to support more robust risk stratification and intervention strategies.
BACKGROUND: Depressive symptoms are common among justice-involved youths, yet access to structured psychological support in correctional settings remains limited. This study examined the short-term effects of a self-dire...BACKGROUND: Depressive symptoms are common among justice-involved youths, yet access to structured psychological support in correctional settings remains limited. This study examined the short-term effects of a self-directed cognitive behavioral therapy (CBT) manual on depressive symptoms among youths incarcerated for drug-related offenses. METHODS: A quasi-experimental two-group pretest-posttest design with a two-week follow-up was conducted among 100 male justice-involved youths in Thailand (50 per group). Participants were incarcerated for drug-related offenses and were receiving routine rehabilitation services within the correctional facility. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CESD). The intervention group completed an eight-session self-directed CBT manual, while the control group received routine care. Group-by-time effects were examined using two-way repeated-measures analysis of variance, with Bonferroni-adjusted pairwise comparisons and standardized effect sizes. RESULTS: A significant group-by-time interaction was observed, F(1.726, 169.185) = 21.412, p < .001, partial eta squared = 0.179. Compared with the control group, the intervention group had lower depressive symptom scores at post-intervention and the two-week follow-up. Within the intervention group, depressive symptom scores decreased significantly from baseline to post-intervention and follow-up, with large within-group effect sizes. CONCLUSIONS: The self-directed CBT manual was associated with short-term reductions in depressive symptom scores among justice-involved youths incarcerated for drug-related offenses. These findings suggest that a structured self-directed CBT manual may be a useful low-intensity psychosocial support option in correctional settings. Further studies using more rigorous designs and longer follow-up periods are warranted.
BACKGROUND: Depressive symptoms are a significant health concern among middle-aged and older adults. While previous studies have linked lower basal metabolic rate (BMR) to higher depression risk, the impact of BMR trajec...BACKGROUND: Depressive symptoms are a significant health concern among middle-aged and older adults. While previous studies have linked lower basal metabolic rate (BMR) to higher depression risk, the impact of BMR trajectories over time on the development of depressive symptoms remains unclear. METHODS: Data from three large, nationally representative cohorts were analyzed: China Health and Retirement Longitudinal Study (CHARLS; n = 3117), Health and Retirement Study (HRS; n = 7284), and Survey of Health, Ageing and Retirement in Europe (SHARE; n = 5353). Group-based trajectory modeling identified BMR trajectories, and logistic regression assessed the association between these trajectories and the onset of depressive symptoms. A random-effects model was used to pool results across cohorts. RESULTS: Three distinct BMR trajectories (low-level, medium-level, high-level) were identified, all showing a consistent decline over time. In CHARLS and HRS, higher BMR trajectories were linked to lower odds of depressive symptoms, while in SHARE, only the high-level trajectory was protective. In the fully adjusted pooled analysis (Model 3), the medium-level (OR = 0.79, 95% CI: 0.71-0.86) and high-level (OR = 0.68, 95% CI: 0.58-0.79) groups had significantly lower odds of depression compared to the low-level group. Older males with low BMR had the highest risk of depressive symptoms (pooled OR = 3.52, 95% CI: 2.17-5.71). CONCLUSION: Among middle-aged and older adults, higher BMR trajectories are consistently associated with a lower risk of incident depressive symptoms. Older males in the low BMR trajectory identified as the highest-risk subgroup.
BACKGROUND: The only efficacious psychosocial intervention for decreasing suicide attempts among adolescents with bipolar disorder (BP) is an adaptation of Dialectical Behavior Therapy (DBT). Yet myriad factors, includin...BACKGROUND: The only efficacious psychosocial intervention for decreasing suicide attempts among adolescents with bipolar disorder (BP) is an adaptation of Dialectical Behavior Therapy (DBT). Yet myriad factors, including clinician training, limit DBT uptake. To enhance dissemination, we systematically operationalized, implemented and studied procedures for training and supervising community clinicians to adherently deliver DBT for adolescents with BP. METHODS: This study was conducted at a University-affiliated clinic serving youth with BP. Guided by the Enhanced-Replicating Effective Programs (E-REP) framework, we focused on internal and external facilitation components. Participants included master's level therapists (n = 3) at the implementation site; expert training and consultation were provided by an independent site. Validated measures of therapist satisfaction and acceptability, barriers and facilitators, and therapist competency were assessed at 0, 6, 12, 24 months using validated measures. RESULTS: Data indicate high satisfaction and acceptability with the DBT approach and supervision model. Therapists initially identified difficulty changing their practice and low patient skills application as barriers; these improved with time. Administrative-level barriers were few, though therapists consistently cited competing demands. Ratings of the implementation climate, specifically perception of the environment's support for DBT, decreased over time (nonsignificant trend). All therapists passed the external DBT certification process by study-end and maintained fidelity through 2-years via independent adherence coding. CONCLUSIONS: The resultant training and supervision model of DBT for adolescents with BP holds promise to inform dissemination efforts for this high-risk population. Data indicate careful attention to therapist- and organizational-level facilitators and barriers should be considered throughout the implementation process. CLINICALTRIALS: govID:NCT03661333.
OBJECTIVE: Anxiety and depression are common mental disorders and frequently coexist with oral health problems (OHPs) that impair overall well-being and quality of life. While the association of mood disorders and OHPs i...OBJECTIVE: Anxiety and depression are common mental disorders and frequently coexist with oral health problems (OHPs) that impair overall well-being and quality of life. While the association of mood disorders and OHPs is well documented in adults, evidence regarding their association in pediatric populations remains unclear. METHODS: We systematically searched PubMed, Embase, Scopus, Web of Science, and reference lists to identify eligible studies. Risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Pooled estimations, including odds ratios (ORs) and standardized mean differences, were calculated with random- or fixed-effects models determined by I-assessed heterogeneity. RESULTS: A total of 33 studies were included, 27 of which were eligible for meta-analysis, involving a total of 31,834 participants across 15 countries. The pooled prevalence of anxiety and depression were 57% (95% CI: 41%-73%) and 38% (95% CI: 20%-56%), respectively, among individuals with OHPs, with considerable heterogeneity. The pooled estimations tended to support the hypothesis that anxiety and depression were significantly associated with OHPs, with Odds Ratios (ORs) of 2.67 (95% CI: 1.43-4.97, I = 89.2%) and 1.93 (95% CI: 1.22-3.04, I = 71.1%). In subgroup analyses, both anxiety and depression appeared to be associated with bruxism and temporomandibular disorders (TMDs). CONCLUSION: Based on the available evidence, anxiety and depression were associated with OHPs, particularly bruxism and TMDs, in pediatric populations. Given the high heterogeneity and methodological variability across included studies, these findings should be interpreted with caution. Multidisciplinary collaboration is recommended to promote both mental and dental health at an early age.
BACKGROUND: Suicide remains a major cause of preventable premature mortality worldwide, yet long-term evidence from middle-income countries remains limited, particularly regarding post-pandemic trajectories, geographic i...BACKGROUND: Suicide remains a major cause of preventable premature mortality worldwide, yet long-term evidence from middle-income countries remains limited, particularly regarding post-pandemic trajectories, geographic inequalities, seasonal variation, and future burden. This study analyzed suicide mortality in Brazil from 2005 to 2024, examining temporal trends, demographic patterns, excess mortality, spatial clustering, seasonality, and projections through 2030. METHODS: We conducted a nationwide ecological time-series study using mortality data from the Brazilian Mortality Information System. Suicide deaths were identified using ICD-10 codes X60-X84. Crude and age-standardized mortality rates were calculated per 100,000 inhabitants. Temporal trends were assessed using regression models, interrupted time-series analysis evaluated pandemic-related changes, and ARIMA models estimated excess mortality and future projections. Sex-specific mortality, spatial autocorrelation, and seasonal patterns were also examined. RESULTS: Brazil recorded 236,474 suicide deaths between 2005 and 2024, increasing from 8550 deaths in 2005 to 16,751 in 2024. Age-standardized mortality increased from 6.24 to 8.67 deaths per 100,000 inhabitants (annual percent change: 2.36%; 95% CI: 1.52-3.20). Men accounted for 78.6% of deaths and had nearly fourfold higher mortality than women (RR = 3.82; 95% CI: 3.71-3.94). Adults aged 20-49 years represented 60.9% of deaths. Mortality accelerated after 2020, exceeded expected levels from 2021 onward, showed clustering in Southern Brazil, peaked in late-year months, and is projected to continue increasing through 2030. CONCLUSIONS: Suicide mortality in Brazil increased substantially between 2005 and 2024 and remained above expected levels from 2021 onward. Although mortality showed a steeper trajectory after 2020, interrupted time-series analyses suggest that these findings should be interpreted as temporal deviations from pre-pandemic trends rather than definitive evidence of a direct pandemic effect.
INTRODUCTION: Alexithymia has been separately associated with differences in white-matter and with substance use (SU). Childhood trauma has also been associated with white-matter differences, alexithymia, and SU. This st...INTRODUCTION: Alexithymia has been separately associated with differences in white-matter and with substance use (SU). Childhood trauma has also been associated with white-matter differences, alexithymia, and SU. This study explored the moderating effect of childhood trauma on the indirect effect of white-matter microstructure on SU escalation through alexithymia. METHODS: Participants were 44 young adults from a larger longitudinal cohort, and data on childhood trauma, alexithymia, white-matter were acquired initially. SU escalation was calculated from the quantity and frequency of SU initially and two-years later. Diffusion-weighted white-matter data were used to calculate tensor-derived and crossing-fiber anisotropy measures. Multivariable analyses and moderated mediation models tested whether the indirect relationship between corpus callosum anisotropy and SU escalation through alexithymia differed between levels of childhood trauma. RESULTS: Splenium primary-fiber anisotropy correlated with lower SU escalation whereas splenium secondary-fiber anisotropy correlated with greater SU escalation and alexithymic difficulty describing feelings. Within moderated mediation models, childhood trauma levels moderated associations between splenium primary-fiber anisotropy and difficulty describing feelings. Conditional effects showed that at greater childhood trauma, lower splenium primary-fiber anisotropy associated with greater difficulty describing feeling, and difficulty describing feelings mediated associations between splenium primary-fiber anisotropy and SU escalation. CONCLUSIONS: Trauma may moderate maladaptive emotion-language processing in individuals with specific white-matter differences, and alexithymia may be directly or indirectly associated with SU escalation. Individuals with early-life trauma and splenium white-matter differences may represent a vulnerable population, which may be an important focus from interventions that bolster stress management and emotion regulation.
Although previous resting-state fMRI studies have revealed functional abnormalities in multiple brain regions of obsessive-compulsive disorder (OCD) patients, the underlying pathological mechanisms remain unclear. As the...Although previous resting-state fMRI studies have revealed functional abnormalities in multiple brain regions of obsessive-compulsive disorder (OCD) patients, the underlying pathological mechanisms remain unclear. As the brain constitutes a complex dynamic system, capturing its dynamic features could advance our understanding of neural activity mechanisms. This study employed hidden Markov modeling (HMM) to investigate dynamic alterations in resting-state brain activity among OCD patients, offering a dynamic perspective on the disorder's pathophysiology. A total of 60 OCD patients and 57 healthy controls (HCs) were enrolled. The HMM was used to identify distinct brain states, characterizing their activation patterns. Temporal features of these states and differences in transition patterns between states were compared between the two groups. Compared to HCs, OCD patients spent significantly more time in the state characterized by mildly elevated global activation (p = 0.024, partial η = 0.070), while spending less time in the state characterized by high activation level in the auditory network (AUD) and salience network (SN), coupled with low activation level in default mode network (DMN) and frontoparietal network (FPN) (p = 0.030, partial η = 0.057). Additionally, OCD patients showed decreased switching rate (p = 0.025, partial η = 0.044) and particular difficulty transitioning from States 1, 2, and 5 into the state characterized by high SN and low DMN activation. These findings suggest altered dynamic patterns of brain network activity in OCD, characterized by abnormal temporal occupancy of specific brain states and reduced switching between states. These alterations may be related to salience network dysfunction and could contribute to our understanding of cognitive inflexibility in OCD from a dynamic perspective. However, further studies are needed to establish the specificity and clinical relevance of these findings.
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with changes in motivation to work for rewards being a core symptom. Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising the...Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with changes in motivation to work for rewards being a core symptom. Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising therapy but its effects on the core features of MDD, such as changes in motivation, remained relatively unexplored. In this randomised, single-blind, cross-over, controlled trial, we used a grip strength effort task to investigate how tVNS impacted choices to exert different levels of physical effort for varying monetary rewards in MDD patients (n = 53) and a non-depressed control group (n = 45). The primary analyses showed no interaction between condition (sham versus tVNS) and group (control versus MDD). However, secondary analyses showed that tVNS effects were dependent on symptom severity. Compared to sham stimulation, tVNS enhanced the efficiency with which participants with severe depressive symptoms allocated physical effort for rewards (reward-effort efficiency). These effects were not seen in healthy participants or MDD patients with less severe symptoms. The effect of tVNS on reward-effort efficiency was driven by reduced unnecessary effort in those with severe MDD symptoms - a reduction in choices to exert additional effort when this was not required to gain a larger reward. This suggests a motivational mechanism by which tVNS exerts its therapeutic effects in severe MDD but these remain secondary findings which should be interpreted with caution. Determining whether the effects of tVNS are linked to broader changes in executive functioning, such as improvements in cognitive flexibility in MDD, should be a key aim for future work.
BACKGROUND: Attitudes toward suicide hold clinical value as indirect indicators of suicide risk in psychiatric outpatients, yet these attitudes are culturally sensitive. Within China's ongoing shift from traditional deat...BACKGROUND: Attitudes toward suicide hold clinical value as indirect indicators of suicide risk in psychiatric outpatients, yet these attitudes are culturally sensitive. Within China's ongoing shift from traditional death taboos and collectivism toward more diversified sociocultural context, examining generational differences in such attitudes and their links to suicidal ideation (SI) can enhance their clinical application. However, no prior study has explored how attitudes toward suicide and their associations with passive and active SI (PSI and ASI) vary by age among in Chinese context. METHODS: This study included 4737 Chinese outpatients (70.5% female; M = 23.22, SD = 11.96). We assessed age differences in four attitudes toward suicidal behaviors, suicidal individuals, family members, and euthanasia. Using time-varying effect modeling and network tree analyses, we then examined their age-varying associations with PSI and ASI from variable-centered and person-centered perspectives, respectively. RESULTS: Attitudes toward suicide tended to be more conservative with increasing age among participants. Accepting attitudes toward suicidal behaviors were positively associated with both PSI and ASI across most ages. Compassionate attitudes toward family members were negatively associated with both types of SI in young and middle-aged adults. Accepting attitudes toward euthanasia were positively associated with PSI and ASI from adolescence through middle adulthood. However, attitudes toward the suicidal individuals consistently showed no association with SI. CONCLUSIONS: Preliminary evidence from this cross-sectional study suggests age-specific associations between attitudes toward and suicidal ideation in Chinese psychiatric outpatients. Further longitudinal research is needed to determine whether addressing these attitudes could inform risk assessment.
BACKGROUND: This post hoc analysis assessed the benefit-risk profile of aripiprazole once-monthly 400 mg (AOM 400) as a long-term maintenance treatment in patients diagnosed with bipolar I disorder (BP-I), using the evid...BACKGROUND: This post hoc analysis assessed the benefit-risk profile of aripiprazole once-monthly 400 mg (AOM 400) as a long-term maintenance treatment in patients diagnosed with bipolar I disorder (BP-I), using the evidence-based metrics of number needed to treat (NNT), number needed to harm (NNH), and the likelihood to be helped or harmed (LHH). METHODS: Data were derived from a double-blind, randomized withdrawal study that evaluated the efficacy and safety/tolerability of AOM 400 versus placebo over 52 weeks (NCT01567527). The main efficacy outcome was the proportion of patients free from recurrence of any mood episode, while the main safety/tolerability outcome was the incidence of patient discontinuation due to treatment-emergent adverse events (TEAEs). RESULTS: Overall, 73.5% of 132 patients randomized to AOM 400 and 48.9% of 133 patients randomized to placebo were free from recurrence of any mood episode at Week 52 (NNT = 5 [95% CI: 3,8]). NNT (95% CI) values were 5 (4, 9), 4 (3, 7), and-116 (not significant) for patients free from recurrence of a manic mood episode, mixed mood episode, and depressive mood episode, respectively. Discontinuation due to TEAEs was lower with AOM 400 (17.4%) versus placebo (25.6%), resulting in a negative NNH. Using an imputed NNH versus placebo of 1000, LHH was 200 for patients free from recurrence of any mood episode relative to discontinuation due to any TEAE at 52 weeks. CONCLUSIONS: Data suggest a favorable benefit-risk profile for AOM 400 versus placebo as a long-term maintenance treatment for BP-I.
OBJECTIVE: Perfectionism is a multidimensional vulnerability factor for depression in young adults, particularly in academic settings. This study examined whether Self-Oriented Perfectionism (SOP) and Socially Prescribed...OBJECTIVE: Perfectionism is a multidimensional vulnerability factor for depression in young adults, particularly in academic settings. This study examined whether Self-Oriented Perfectionism (SOP) and Socially Prescribed Perfectionism (SPP), used as indicators conceptually aligned with perfectionistic strivings and concerns, were prospectively associated with current major depressive episode (MDE) among higher education students. PARTICIPANTS: Participants were 10,460 university and college students aged 18-35 years from the national Norwegian SHOT2022 survey who completed a self-administered diagnostic follow-up approximately one year later. METHODS: Perfectionism was assessed in 2022 using the Eating Disorder Inventory Perfectionism subscale. Current MDE was assessed in 2023 using a self-administered computerized version of the Composite International Diagnostic Interview (CIDI 5.0), based on DSM-5 criteria. Associations were examined using sex-stratified logistic regression models. Linear, quadratic, and restricted cubic spline models were compared to evaluate non-linear associations. RESULTS: Current MDE was present in 17.0% of women and 10.8% of men. Higher SOP and SPP scores were associated with higher prevalence of current MDE at follow-up. Linear ORs per 1-point increase ranged from 1.13 to 1.16 for SOP and SPP across sexes. Model comparisons supported non-linear associations. Estimated MDE prevalence was lowest at low-to-moderate perfectionism scores and increased at the upper end of the score distributions, reaching approximately 40% for SOP and SPP among women and approximately 30% among men. CONCLUSIONS: EDI-P perfectionism scores were prospectively associated with current MDE in a non-linear manner. Findings support nuanced prevention and clinical approaches to perfectionism among higher education students.
AIM: Although Major depressive disorder with mixed features (DMF) is recognized as a clinically distinct subtype, its underlying electrophysiological signatures remain unknown. This study aimed to investigate subtype-spe...AIM: Although Major depressive disorder with mixed features (DMF) is recognized as a clinically distinct subtype, its underlying electrophysiological signatures remain unknown. This study aimed to investigate subtype-specific alterations in resting-state alpha band oscillations between DMF and Major depressive disorder without mixed features (nDMF), as well as the relationship of these oscillations with white matter structure. METHODS: We collected resting-state magnetoencephalography (MEG) and diffusion tensor imaging (DTI) data from 197 participants. The cohort comprised 86 healthy controls (HC), 35 patients with DMF, and 76 nDMF. We analyzed alpha band functional connectivity across all participants and, in a subsample, examined global and regional structural-functional (SC-FC) coupling. The relationship of these neuroimaging metrics with clinical features was assessed. RESULTS: DMF patients showed higher alpha-band connectivity between the right supplementary motor area (SMA.R) and right anterior cingulate gyrus (ACC.R) than nDMF patients, and uniquely enhanced SC-FC coupling in the left anterior cingulate gyrus (ACC.L) versus both nDMF and HC groups, which negatively correlated with the subthreshold (hypo)manic symptom items. Conversely, nDMF patients exhibited higher connectivity between the SMA.R and the right middle temporal gyrus (TPOmid.R) than both DMF and HC groups. Both patient groups shared increased connectivity between the SMA.R and the right superior parietal gyrus (SPG.R) relative to HC group. CONCLUSION: Our findings support DMF as a neurobiologically distinct subtype, characterized by a dissociable pattern of alpha band connectivity and SC-FC coupling, providing a multimodal framework for refining diagnostic precision in depressive disorders.
BACKGROUND: Major depressive disorder (MDD) ranks among the foremost contributors to disability worldwide, yet its neurophysiological mechanisms remain poorly understood. Excitation-inhibition (E/I) imbalance has been im...BACKGROUND: Major depressive disorder (MDD) ranks among the foremost contributors to disability worldwide, yet its neurophysiological mechanisms remain poorly understood. Excitation-inhibition (E/I) imbalance has been implicated in MDD pathophysiology, but cortex-wide E/I ratio and its molecular substrates in MDD remain unknown. METHODS: Resting-state functional magnetic resonance imaging data from 254 MDD patients and 451 healthy controls (HCs) across six sites were analyzed. The Hurst exponent, a biophysically confirmed proxy of E/I balance, was estimated using a fractionally integrated process framework. Neurobiological decoding analyses were performed to map the transcriptomic and neurochemical signatures of cortical E/I imbalance in MDD. An independent ketamine clinical trial dataset (32 treatment-resistant depression patients and 21 HCs) was used to examine ketamine-induced changes in cortical E/I balance. RESULTS: Patients with MDD demonstrated significantly reduced Hurst exponent values, predominantly encompassing the parietal and prefrontal-cingulate cortices. Transcriptomic analysis identified enrichment for neuronal structural organization, nucleic acid metabolism, and mitochondrial function, with preferential overlap with excitatory and inhibitory neuron-specific gene sets. Neurochemically, Hurst exponent alterations were spatially associated with GABAergic, opioidergic, serotonergic, and synaptic density distributions. Divergent group-by-treatment effects were observed in the anterior cingulate and medial prefrontal cortices, with ketamine-induced increases in TRD patients. CONCLUSION: These findings highlight that prefrontal-cingulate E/I imbalance, anchored to specific transcriptional and neurochemical substrates, may underlie the pathophysiology of MDD and the antidepressant effects of ketamine. The Hurst exponent offers a promising neuroimaging approach for probing E/I imbalance and identifying potential treatment targets in depression.
Schizophrenia (SCZ) and major depressive disorder (MDD) are severe psychiatric disorders with substantial shared genetic liability and frequent clinical co-occurrence, yet their shared cell type-specific genetic mechanis...Schizophrenia (SCZ) and major depressive disorder (MDD) are severe psychiatric disorders with substantial shared genetic liability and frequent clinical co-occurrence, yet their shared cell type-specific genetic mechanisms remain unclear. We integrated single-cell expression quantitative trait locus (sc-eQTL) data from eight major brain cell types with large-scale genome-wide association study (GWAS) summary statistics for SCZ and MDD. Cell type-specific genetically regulated gene expression was evaluated using Mendelian randomization (MR) and Bayesian colocalization analyses, followed by validation in independent single-cell RNA sequencing datasets and functional characterization using virtual gene knockout and phenome-wide association study (PheWAS) analyses. Integrative analyses prioritized three shared candidate genes, ZSCAN31, BTN3A2, and YLPM1, all showing strong colocalization support (PP·H4 > 0.8). Single-cell transcriptomic validation supported distinct cell type-specific patterns, with ZSCAN31 enriched in astrocytes and endothelial cells, BTN3A2 in microglia, and YLPM1 in oligodendrocytes. Virtual knockout of YLPM1 suggested perturbation of neurodevelopment-related pathways in SCZ and synaptic signaling pathways in MDD. These findings provide a cell type-resolved view of shared genetic architecture between SCZ and MDD and highlight candidate genes for further mechanistic and translational investigation.