Patients with bipolar disorder (BD) exhibit deficits in emotional conflict control. These abnormalities may be related to alterations in distinct cognitive subprocesses involved in emotional conflict processing; however,...Patients with bipolar disorder (BD) exhibit deficits in emotional conflict control. These abnormalities may be related to alterations in distinct cognitive subprocesses involved in emotional conflict processing; however, the specific stages affected remain unclear. Given the temporal and stage-dependent nature of emotional conflict control, examining specific processing stages may clarify the mechanisms underlying these deficits in BD. Therefore, this study combined a face-word emotional Stroop task with EEG, integrating event-related potentials (ERPs) and brain functional network analyses to characterize the cognitive subprocesses involved in emotional conflict control in bipolar II disorder (BD-II). BD-II patients showed significant abnormalities in early cognitive stages, including emotional stimulus perception and conflict monitoring (p < 0.05). These abnormalities were mainly reflected by reduced N200 amplitudes, right temporal region (T8)-centered network changes, and alterations in both global topology and frontal network organization. Machine learning analysis further suggested that these abnormal electrophysiological features may contain information relevant to distinguishing BD-II patients from healthy controls (HC), yielding an accuracy of 83.3% on the held-out test set. In summary, this study suggests that emotional conflict control deficits in BD-II are mainly reflected in early-stage electrophysiological abnormalities, with ERP amplitude changes and T8-centered right temporal network alterations representing the core findings. These findings provide candidate EEG features for further investigation of emotional conflict control abnormalities in BD-II, but require validation in larger independent samples.
BACKGROUND: Peer support has a long history of being offered through community programs, and is increasingly formalized in mental health services to facilitate recovery-oriented care for mental health concerns such as bi...BACKGROUND: Peer support has a long history of being offered through community programs, and is increasingly formalized in mental health services to facilitate recovery-oriented care for mental health concerns such as bipolar disorder (BD). This qualitative study explored experiences of community-based peer support programs from the perspective of people with BD, to generate insights to optimise the delivery of peer support in clinical settings. METHODS: Adults living in Canada with BD, who had participated in or provided peer support, participated in one of five 90-min focus groups. Participants were questioned about interacting with peers, helpful and unhelpful group aspects, and facilitators of positive outcomes. Thematic analysis was used to identify key aspects of peer support. RESULTS: Sixteen individuals with BD (81% women) participated in qualitative focus groups. Four overarching themes were generated to describe the benefits, challenges, and conduct of peer support: 1) Someone who knows what it's like, 2) Learning from one another, 3) Challenging interpersonal dynamics, 4) A good facilitator makes a world of difference. CONCLUSIONS: While findings may have been weighted towards the perspectives of individuals with positive experiences, they generate future research questions regarding peer support processes and outcomes that are as yet understudied in the BD literature. Including lived experience perspectives in the design of evaluation studies is therefore recommended to ensure patient-valued outcomes are included. Given the critical role of facilitation in safeguarding against challenging experiences, investment in co-designed training programs is called for, leveraging the expertise of community programs.
The error-related negativity (ERN) is a measurable brain response to mistakes that is thought to reflect a modifiable cognitive/emotional bias contributing to the development of anxiety disorders. We previously demonstra...The error-related negativity (ERN) is a measurable brain response to mistakes that is thought to reflect a modifiable cognitive/emotional bias contributing to the development of anxiety disorders. We previously demonstrated that a psychosocial intervention to reduce error sensitivity can reduce the ERN among (nonclinical) adults and children who have relatively large ERNs. We have also demonstrated that a brain response (balance N1) evoked by a disturbance to standing balance shares the ERN's relationship to anxiety. We hypothesized that if ERN and N1 reflect the same underlying brain mechanisms, then an intervention to reduce the ERN should similarly reduce the balance N1. In this pre-registered randomized controlled trial, 54 children with anxiety disorders (age 9-12 years) were randomized into either a brief (45-min) single-session computerized psychosocial intervention to reduce error sensitivity, or a similarly formatted control condition. Primary outcome measures were changes in the ERN (measured in a Go/NoGo task) and balance N1 (measured in a lean-and-release balance task). The ERN was reduced after the psychosocial intervention, while the balance N1 remained unchanged. A brief computerized psychosocial intervention to reduce error sensitivity can reduce the ERN among clinically anxious children, but the limited effect may warrant a larger dosage. Discrepant outcomes between the ERN and balance N1 suggest the intervention targets mechanisms not shared between these brain responses. We speculate the intervention may have helped children manage overreactions to trivial mistakes while preserving the inherent significance of a loss of balance. CLINICAL TRIAL REGISTRATION: Computerized intervention targeting the error-related negativity and balance N1 in anxious children. https://clinicaltrials.gov/study/NCT05503017.
Approximately one billion people worldwide live with a mental disorder, yet access to minimally adequate treatment remains low. Against this backdrop, general-purpose generative artificial intelligence (GenAI) systems ha...Approximately one billion people worldwide live with a mental disorder, yet access to minimally adequate treatment remains low. Against this backdrop, general-purpose generative artificial intelligence (GenAI) systems have rapidly expanded into informal mental health support. OpenAI disclosed that roughly 1.2 million ChatGPT users weekly display indicators of suicidal planning or intent, and meta-analytic evidence supports modest efficacy for AI chatbots in reducing common mental health symptoms. Nevertheless, these tools may pose substantial clinical risks for vulnerable individuals. Two interlocking mechanisms-algorithmic sycophancy and anthropomorphic projection-converge to produce self-reinforcing engagement-validation loops capable of reinforcing maladaptive beliefs and contributing to clinical risk. Structural investment in mental-health workforce capacity must remain the foundation of future responses to the global treatment gap, with GenAI deployed as a supervised adjunct to clinicians within hybrid stepped-care frameworks subject to independent safety evaluation, transparent disclosure obligations, and regulatory oversight proportional to clinical risk.
BACKGROUND: Depressive symptoms are major determinants of outcome in bipolar disorder. We examined whether baseline anhedonia-related symptom severity was associated with subsequent clinical wellness. METHODS: We analyze...BACKGROUND: Depressive symptoms are major determinants of outcome in bipolar disorder. We examined whether baseline anhedonia-related symptom severity was associated with subsequent clinical wellness. METHODS: We analyzed longitudinal data from the STEP-BD, a multicenter naturalistic effectiveness study of bipolar disorder. The primary predictor was baseline MADRS item 8 ("Inability to Feel") score. The primary outcome was the first-year proportion of days well. Secondary outcomes were functioning (LRIFT) and quality of life (Q-LES-Q). Core models adjusted for baseline MADRS total excluding item 8, YMRS total, age, sex, bipolar II diagnosis, and age-at-onset category. Sensitivity analyses included multiple imputation, treatment-adjusted models, categorical item 8 specifications, nonlinearity testing, and negative binomial regression. RESULTS: The primary analytic sample included 2576 participants. Higher baseline MADRS item 8 scores were associated with a lower first-year proportion of days well (p < 0.001; standardized β = -0.088; incremental R = 0.004 over a model including all other covariates). The adjusted predicted difference between scores 0-3 corresponded to approximately 18 fewer days well per year. The association was robust across multiple sensitivity analyses including multiple imputation, treatment-adjusted models, and categorical specifications. It did not significantly predict follow-up LRIFT or Q-LES-Q. CONCLUSION: Baseline inability to feel was modestly but consistently associated with fewer first-year days well in bipolar disorder, independent of overall depressive severity and major clinical covariates. The effect size was small and did not extend to functioning or quality of life after accounting for baseline levels of those outcomes.
BACKGROUND: Complex Post-Traumatic Stress Disorder (CPTSD) is a significant mental health concern in adolescents, however traditional diagnostic tools often fail to capture early risk patterns. Adolescence is a unique de...BACKGROUND: Complex Post-Traumatic Stress Disorder (CPTSD) is a significant mental health concern in adolescents, however traditional diagnostic tools often fail to capture early risk patterns. Adolescence is a unique developmental window marked by neurobiological remodeling and heightened interpersonal sensitivity. This study aims to move beyond binary clinical diagnosis toward a subclinical prevention framework by predicting continuous CPTSD symptom severity using multidimensional ecological data. METHODS: The data were collected from a triad of 4177 Chinese adolescents and their parents. A two-layer stacking ensemble machine learning model was employed to integrate 118 variables across individual, family, and school domains. SHapley Additive exPlanations (SHAP) analysis was utilized to provide interpretability and identify the predictive contribution of key ecological factors. RESULTS: The stacking ensemble model demonstrated higher predictive accuracy in identifying complex ecological risk patterns compared to standalone base learners. School climate functioned as an asymmetrical indicator where deterioration significantly predicted symptom elevation while a positive climate offered a limited protective association. Peer victimisation behaviors, maternal anxiety, and paternal coparenting conflict were identified as core components of the risk patterns. CONCLUSION: An interpretable stacking ensemble model is developed to estimate concurrent CPTSD symptom severity in adolescents using multiple informant ecological data. Peer victimisation behaviors, maternal anxiety, and school climate are identified as the most informative indicators. A temporal inference is precluded by the cross sectional design. Therefore, this framework is viewed as an exploratory approach to recognizing adolescents with an elevated concurrent symptom burden.
BACKGROUND: Major depressive disorder (MDD) and social anxiety disorder (SAD) are prevalent and frequently co-occurring. Few studies have directly compared MDD and SAD using spatially and frequency-resolved resting-state...BACKGROUND: Major depressive disorder (MDD) and social anxiety disorder (SAD) are prevalent and frequently co-occurring. Few studies have directly compared MDD and SAD using spatially and frequency-resolved resting-state functional connectivity (rsFC). We examined whether rsFC networks show shared and diagnosis-associated features of MDD and SAD. METHODS: Baseline rsFC from 150 adults (MDD = 60; SAD = 55; healthy controls [HC] = 35) underwent group-information-guided ICA (GIG-ICA). Component spatial maps and frequency spectra were compared across groups with age, sex, and motion covariates. Follow-up regressions related ICA features to Hamilton Depression Rating Scale (HAM-D) and Liebowitz Social Anxiety Scale (LSAS). Robustness analyses evaluated motion, comorbidity, illness/treatment history, sex balance, and preprocessing choices. RESULTS: Relative to SAD, MDD showed reduced low-frequency rsFC in the salience network (SN; 0.045-0.058 Hz) and superior temporal gyrus (STG; 0.037-0.041, 0.054-0.093 Hz), whereas SAD showed greater fusiform/parahippocampal (FusPHG) spatial-map expression. FusPHG correlated positively with LSAS (β = 0.425, p < .001) and negatively with HAM-D (β = -0.375, p < .001). SN connectivity correlated negatively with HAM-D and LSAS, while STG connectivity correlated negatively with LSAS but not HAM-D. Parsimonious sensitivity models identified FusPHG spatial expression and STG 0.054-0.093 Hz power as the most stable candidate group-level associations; SN effects attenuated after fuller illness-course and lifetime-treatment proxy adjustment. CONCLUSIONS: MDD and SAD showed candidate spatially and frequency-resolved network differences involving SN, STG, and FusPHG circuits. These preliminary findings indicate SAD and MDD differ in neural pathways linking salience-related control, social-auditory integration, and visual-affective simulation and require replication.
BACKGROUND: Suicide remains a significant global public health issue. Positive psychological interventions (PPIs) have been proposed as approaches that may contribute to suicide prevention, although their effectiveness r...BACKGROUND: Suicide remains a significant global public health issue. Positive psychological interventions (PPIs) have been proposed as approaches that may contribute to suicide prevention, although their effectiveness remains unclear. METHODS: We systematically searched 11 databases from inception to January 2026. Pooled effect sizes were synthesized primarily using random-effects models. Subgroup, sensitivity, and meta-regression analyses were conducted to explore heterogeneity and test robustness. RESULTS: Sixteen studies were included in the systematic review, 12 in the meta-analysis. At post-treatment, PPIs were associated with reduced suicidal ideation (Hedges' g = -0.39, 95% CI: -0.74 to -0.04). Evidence for persistence at post-intervention assessment was limited because only three studies reported short-term post-intervention assessments (Hedges' g = -0.12, 95% CI: -0.40 to 0.17). Evidence on suicide attempts and death by suicide was sparse (n = 5), although one study reported superior outcomes with PPIs versus control (log-rank χ = 4.85, p = 0.028). In subgroup analyses, PPIs showed greater effects versus waitlist/blank controls (Hedges' g = -0.63, 95% CI: -0.86 to -0.40). Preliminary evidence suggests greater reductions in suicidal ideation with PPIs combined with pharmacotherapy than with pharmacotherapy alone (Hedges' g = -1.06, 95% CI: -1.70 to -0.42). Larger pooled effects were observed in low- and middle-income countries than in high-income countries (p = 0.029). Meta-regression showed control type (β = -0.414, p < 0.001) and total number of intervention sessions (β = -0.061, p = 0.043) explained 73.84% and 29.40% of between-study heterogeneity, respectively. CONCLUSION: PPIs may have supportive or adjunctive value for suicide-related psychological outcomes, but evidence for suicide attempts, death by suicide, and longer-term effects remains limited.
BACKGROUND: There is a pressing need to identify objective biomarkers for adolescent major depressive disorder (MDD). This study aimed to assist in identifying neuroimaging biomarkers based on cortical hemodynamic respon...BACKGROUND: There is a pressing need to identify objective biomarkers for adolescent major depressive disorder (MDD). This study aimed to assist in identifying neuroimaging biomarkers based on cortical hemodynamic responses using machine learning. METHOD: A total of 197 adolescents (114 adolescents with MDD and 83 healthy controls) completed both a verbal fluency task (VFT) and a working memory (WM) task during functional near-infrared spectroscopy (fNIRS) recording. Five machine learning algorithms were applied to build identification model. RESULT: Adolescents with MDD showed reduced mean oxyhemoglobin (Oxy-Hb) activation in frontotemporal regions during both VFT and WM tasks, accompanied by altered slope feature. The combined VFT-WM model achieved the best performance, with Random Forest both reaching an area under the curve (AUC) of 0.93. The slope of the right superior frontal gyrus, derived from the working memory retrieval phase, was the most influential feature in the Random Forest model, with the highest contribution (mean |SHAP| = 0.07). Subgroup analysis showed improved performance in patients with longer disease duration (Random Forest and SVM AUC = 0.96). CONCLUSION: WM-related prefrontal hemodynamic features, particularly retrieval-related dynamic responses, may serve as promising neuroimaging biomarkers of adolescent MDD. Integrating task-based fNIRS with interpretable machine learning may facilitate the objective identification of adolescent MDD. Given the inpatient sample, the model may be better suited for supporting diagnosis in clinically established cases rather than for early screening.
BACKGROUND: The glymphatic system is essential for cerebral waste clearance. This study evaluated glymphatic function in major depressive disorder (MDD) and bipolar disorder (BD) by combining diffusion tensor imaging alo...BACKGROUND: The glymphatic system is essential for cerebral waste clearance. This study evaluated glymphatic function in major depressive disorder (MDD) and bipolar disorder (BD) by combining diffusion tensor imaging along the perivascular space (DTI-ALPS) and global blood‑oxygen-level-dependent (gBOLD)-cerebrospinal fluid (CSF) coupling, exploring associations with affective, sleep, and cognitive symptoms. METHODS: We recruited 52 MDD patients, 31 BD patients, and 52 healthy controls (HCs) for multimodal magnetic resonance imaging (MRI). Glymphatic function was assessed via DTI-ALPS and gBOLD-CSF coupling. Standardized scales evaluated depression, anxiety, sleep disturbances, cognition, and anhedonia. Inter-group comparisons, correlation, regression, mediation, and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: MDD and BD patients exhibited significantly reduced DTI-ALPS indices and gBOLD-CSF coupling compared to HCs, with no significant differences between patient groups. Exploratory analyses indicated these indirect imaging markers were intercorrelated weakly but significantly. Additionally, modality-specific alterations correlated with cognitive decline and increased anhedonia in MDD, and poorer sleep in BD. ROC analysis showed the joint imaging model provided modest diagnostic performance for distinguishing patients from HCs, which improved when integrated with clinical variables. Furthermore, mediation analysis suggested gBOLD-CSF coupling statistically mediated the association between disease status and affective symptoms. CONCLUSIONS: Glymphatic impairment is a shared feature of MDD and BD. DTI-ALPS and gBOLD-CSF coupling serve as complementary, indirect biomarkers linked to core clinical features. While causal relationships remain to be elucidated, targeting glymphatic function may offer a novel therapeutic avenue for mood disorders.
Marques-Feixa L, Moreno-Gamazo N, Romero S
… +10 more, March-Llanes J, Mas A, Rapado-Castro M, Blasco-Fontecilla H, Zorrilla I, Monteserín JL, Muñoz MJ, San Martín-González N, Fañanás L, EPI_Young_Stress Group
Child maltreatment (CM) significantly impacts developing brains and bodies, increasing the risk of clinical conditions. Allostatic load (AL), conceptualized as an index of cumulative biological dysregulation, may functio...Child maltreatment (CM) significantly impacts developing brains and bodies, increasing the risk of clinical conditions. Allostatic load (AL), conceptualized as an index of cumulative biological dysregulation, may function as a vulnerability marker that modifies the strength of the association between CM and emotional/behavioral symptoms. We aim to gain a better understanding of the mental health challenges in children and adolescents proximally exposed to CM and associated AL profiles. We studied 187 children and adolescents (7-17 years old) with and without current psychopathology. CM history was assessed using the TASSCV, and emotional/behavioral symptomatology with the CBCL. An AL index was derived from 10 biomarkers spanning neuroendocrine, immune, metabolic, and anthropometric systems, including diurnal cortisol output, cortisol reactivity, s-IgA output and reactivity during acute stress, CRP, glucose, HbA1c, total-to-HDL cholesterol ratio, BMI, and waist-to-height ratio (WHtR). Each participant received a risk score based on established clinical cut-offs to construct the composite AL-index. Findings indicated that CM was associated with higher AL scores (B = 0.18, p < .05), and AL significantly moderated the association between CM and emotional/behavioral symptomatology (B = 3.52, p < .05), particularly internalizing symptoms (B = 1.38, p < .05) and social problems (B = 0.48, p < .01). Notably, a combination of three biomarkers (diurnal cortisol, CRP and WHtR), most strongly predicted psychopathology severity in CM-exposed youth (B = 6.21, p < .05). In conclusion, children and adolescents with a history of CM already show increased AL, which reflects a state of biological vulnerability that amplifies the association between CM and mental health challenges. The 3-biomarker AL-index may represent a useful exploratory tool to identify individuals with more severe transdiagnostic symptom profiles.
BACKGROUND: A prior suicide attempt is the strongest predictor of subsequent suicide mortality in major depressive disorder (MDD); however, the functional network architecture distinguishing individuals with and without...BACKGROUND: A prior suicide attempt is the strongest predictor of subsequent suicide mortality in major depressive disorder (MDD); however, the functional network architecture distinguishing individuals with and without a history of suicide attempts remains incompletely characterized. We applied a connectome-wide functional connectivity (FC) framework to identify FC alterations associated with suicide attempt history in MDD and examine their relationships with suicidal ideation and childhood trauma. METHODS: Resting-state functional magnetic resonance imaging data were obtained from 204 participants (suicidal depression [SD] = 61, non-suicidal depression [NSD] = 62, healthy controls [HC] = 81). FC matrices were constructed using the Schaefer 400-node atlas. Group differences were examined using network-based statistics (NBS) and graph-theoretical measures. RESULTS: NBS identified a significant subnetwork exhibiting lower FC in the SD group than in the NSD group (pFWE = 0.038), spanning the visual (VIS), somatomotor (SMN), dorsal attention (DAN), frontoparietal (FPN), and default mode (DMN) networks. Compared with the HC group, the SD group exhibited hypo- and hyperconnected subnetworks, whereas the NSD group showed no significant differences in FC. Graph-theoretical analyses revealed reduced strength, global efficiency, and betweenness centrality within the SD < NSD subnetwork. In the MDD group, mean subnetwork FC, SMN-VIS, and DMN-DMN FC were negatively correlated with suicidal ideation. In the SD group, SMN-SMN FC correlated inversely with childhood sexual abuse. CONCLUSIONS: These findings suggest that hypoconnectivity across sensory, attentional, and self-referential systems may represent a connectome-level signature of suicide vulnerability in MDD and link childhood sexual abuse to suicide risk.
OBJECTIVE: Little is known about esketamine's effectiveness for patients with major depressive disorder (MDD) comorbid substance use disorders (SUD). METHODS: We conducted a retrospective cohort study using the TriNetX U...OBJECTIVE: Little is known about esketamine's effectiveness for patients with major depressive disorder (MDD) comorbid substance use disorders (SUD). METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults aged ≥18 years with MDD. Three propensity-score-matched (1:1) cohorts were defined based on treatment: esketamine, antidepressant-only, and repetitive transcranial magnetic stimulation (rTMS). We calculated relative risks (RRs) to compare the prevalence of substance use disorder (SUD) across these groups. Among esketamine users, we employed Cox proportional hazards models to analyze clinical outcomes-including self-harm, suicide attempt, hospitalization, emergency visits, and mortality-comparing those with and without SUD from the first esketamine prescription. RESULTS: Esketamine users (n = 30,670) showed higher risks of comorbid SUD across all categories versus matched antidepressant and rTMS patients. Compared to the antidepressant group, the highest risks were for hallucinogen (RR 2.41, 95% CI 1.87-3.09), opioid (RR 2.26, 95% CI 2.14-2.37), and stimulant (RR 2.17, 95% CI 2.01-2.34). Elevated risks were also observed versus the rTMS group, with the highest for opioid (RR 3.70, 95% CI 3.14-4.35). Within the esketamine cohort, the presence of comorbid SUD was associated with higher risks for self-harm (HR 2.99, 95% CI 2.29-3.91), suicide attempt (HR 2.13, 95% CI 1.59-2.85), emergency visits (HR 1.78, 95% CI 1.70-1.85), hospitalization (HR 1.70, 95% CI 1.63-1.77), and mortality (HR 1.12, 95% CI 1.04-1.21). CONCLUSION: Esketamine prescription bias toward MDD patients with comorbid SUD underscores the need for enhanced monitoring and specialized care.
BACKGROUND: Interactive tele-mental health (TMH) interventions have been increasingly used to address mental health issues during the perinatal period. However, their effectiveness across perinatal stages remains unclear...BACKGROUND: Interactive tele-mental health (TMH) interventions have been increasingly used to address mental health issues during the perinatal period. However, their effectiveness across perinatal stages remains unclear. This study aimed to evaluate and compare the effectiveness of TMH interventions for depressive and anxiety symptoms across pregnancy, the perinatal period, and the postpartum period. METHODS: PubMed, Embase, Web of Science, Cochrane Library, PsycINFO, CINAHL, ClinicalTrials.gov, CNKI, and Wanfang were searched up to December 2025 to identify randomized controlled trials (RCTs) comparing TMH with usual care or other control conditions. Standardized mean differences (SMDs) were pooled using a random-effects model. RESULTS: A total of 23 RCTs were included. TMH interventions significantly reduced depressive symptoms (SMD = -0.65, 95% CI -0.95 to -0.35; I = 95.2%) and anxiety symptoms (SMD = -0.69, 95% CI -1.01 to -0.36; I = 94.1%). Subgroup analyses showed significant improvements in the postpartum period, while pregnancy and perinatal period effects were not statistically significant. Secondary outcomes indicated reduced maternal stress and improved self-efficacy and social support. CONCLUSIONS: TMH interventions were associated with reductions in depressive and anxiety symptoms, with the strongest effects observed during the postpartum period. Further high-quality studies are needed to evaluate long-term effectiveness and identify optimal intervention strategies.
BACKGROUND: Subthreshold depression (StD) in adolescence is clinically important, but its neurobiological substrates remain unclear. We examined whether adolescents with StD show multimodal MRI alterations related to gly...BACKGROUND: Subthreshold depression (StD) in adolescence is clinically important, but its neurobiological substrates remain unclear. We examined whether adolescents with StD show multimodal MRI alterations related to glymphatic function. METHODS: We recruited 107 adolescents (71 StD, 36 healthy controls). Six glymphatic-related biomarkers were assessed: choroid plexus volume, BOLD-CSF coupling, CSF Hurst exponent, ALPS index, perivascular space volume, and basal forebrain cholinergic nucleus volume. Group differences were tested using age- and sex-adjusted ANCOVA. Biomarker-clinical associations were examined using partial correlations with biomarker-wise Bonferroni correction across five primary clinical scales. Mahalanobis distance (MD) quantified multivariate deviation from the healthy-control glymphatic profile. RESULTS: Compared with controls, adolescents with StD showed reduced BOLD-CSF coupling (F = 4.14, p = 0.044) and lower left ALPS (F = 9.12, p = 0.003). Three associations survived Bonferroni correction: lower left ALPS was associated with greater insomnia severity (p_Bonf = 0.021) and self-rated depressive symptoms (p_Bonf = 0.016), and lower CSF Hurst exponent with higher PHQ-9 scores (p_Bonf = 0.029). MD was higher in StD (F = 6.17, p = 0.01) and showed the strongest clinical association with PHQ-9 severity (r = 0.403, p = 0.001). CONCLUSIONS: Adolescents with StD exhibit a multivariate glymphatic-related MRI profile involving altered BOLD-CSF coupling, reduced left ALPS, and clinically relevant deviations across biomarkers. These findings provide preliminary evidence that glymphatic-related MRI alterations may represent a neurobiological feature of adolescent StD and support multimodal integration over reliance on any single indirect marker.