Journal of Affective Disorders Reports

Post-traumatic stress disorder (PTSD) is associated with high rates of comorbid personality disorders, which may contribute to PTSD severity. Among veterans with PTSD, obsessive compulsive personality disorder (OCPD) is common, with reported prevalence estimates ranging from 7-44%. Despite this, the relationship between OCPD traits and PTSD severity remains poorly understood. This retrospective, cross-sectional study examined associations between PTSD severity and OCPD traits in a naturalistic sample of 99 Veterans evaluated by a single clinician in a PTSD/Trauma Recovery Services clinic. PTSD symptoms were measured with the PTSD Checklist for DSM-V (PCL-5), and OCPD traits were measured with the Pathological Obsessive-Compulsive Personality Scale (POPS). Relationships between these two constructs were examined using Pearson correlations. Overall PTSD severity was significantly and positively correlated with total OCPD traits (r = 0.46, p < 0.001). Among OCPD domains, maladaptive perfectionism showed the strongest association with PTSD severity (r = 0.44, p <.001), followed by emotional overcontrol and reluctance to delegate (both r = .38, p < .01), rigidity (r = .35, p < .01), and difficulty with change (r = .28, p < .05). These findings suggest OCPD traits impact PTSD symptom burden in veterans, warranting further research and clinical attention.

Background Emotionally Unstable Personality Disorder (EUPD) is characterised by emotional dysregulation, unstable self-identity, interpersonal difficulties, dissociation, and a high prevalence of non-suicidal self-injury (NSSI). Mental imagery plays a role in emotion processing and autobiographical memory. Yet little is known about the relation between voluntary visual imagery and self-harm in EUPD. The study aimed to examine the imagery characteristics, including visual imagery vividness and synaesthetic-like experiences, and their association with NSSI in EUPD. Method Forty adults aged 18-45 years meeting ICD-10 Diagnostic Criteria for Research (ICD-10 DCR) for EUPD were recruited through purposive sampling. Visual imagery was assessed using the Vividness of Visual Imagery Questionnaire-2 (VVIQ-2). NSSI and its functions were assessed using the Inventory of Statements About Self-Injury (ISAS). Synaesthesia-like experiences were screened using a seven-item questionnaire developed for the study. Group comparisons were performed using independent-samples t-tests, and correlations were assessed using Pearson's correlation coefficient. Results Twenty-nine patients (72.5%) with EUPD had NSSI. Participants with NSSI had significantly higher mean VVIQ-2 scores than those without NSSI (118.48 +/- 24.81 vs. 93.36 +/- 35.66; p = 0.016; Cohen's d = 0.89). VVIQ-2 scores correlated positively with intrapersonal ISAS functions (r = 0.38, p = 0.015) but not interpersonal functions (r = 0.19, p = 0.22). Three participants (7.5%) demonstrated imagery scores compatible with probable hyperphantasia. Four participants reported synaesthesia-like experiences. Conclusions Greater visual imagery was associated with non-suicidal self-harm in patients with EUPD. Imagery vividness was predominantly associated with intrapersonal functions of non-suicidal self-harm, particularly affect regulation, rather than interpersonal motivations. These findings suggest that visual imagery may represent a previously under-recognized cognitive factor contributing to emotional dysregulation and self-injurious behaviour in EUPD. Assessment of imagery characteristics may have clinical relevance when designing psychotherapeutic interventions for EUPD.

Background: Substance use is common among individuals with depression. Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but current clinical guidelines have discouraged TMS treatment for individuals with depression and co-occurring substance use given concerns for limited efficacy. However, limited data exists on whether substance use affects response to TMS. Methods: Using electronic health record data from patients who received a standard course of TMS for major depressive disorder at an academic medical center, we investigated associations between substance use frequency and response to TMS, defined as change in Patient Health Questionnaire-9 (PHQ-9) scores. Substance use frequency was extracted for alcohol, cannabis, nicotine, stimulants, benzodiazepines, opioids, inhalants, psychedelics, and other drugs. We performed ANCOVA and multiple regression analyses to predict change in PHQ-9 score based on substance use frequency, controlling for pre-TMS PHQ-9 score, age, sex, and number of TMS sessions received. Results: We extracted data from 219 TMS courses. Alcohol was the substance used most commonly (34.2%), followed by prescription benzodiazepines (28.3%), and prescription stimulants (21.0%). Across all substance categories, substance use was not associated with change in PHQ-9 score (all p > 0.05, Cohens d=0.00 to 0.30). In multiple regression models to compare individual levels of substance use frequency (e.g., daily use vs. no use), level of substance use was not associated with change in PHQ-9 score (all p > 0.05). The range of plausible effects of substance use frequency on PHQ-9 change was generally below the minimal clinically important difference for PHQ-9, suggesting substance use was unlikely to have a meaningful clinical effect on antidepressant response to TMS. Conclusions: Low to moderate substance use does not have a clinically significant effect on antidepressant response to TMS. Low-level substance use should not exclude individuals with depression from receiving TMS.

Population-based studies of common mental health conditions (anxiety, depression, post-traumatic stress disorder) require measures that are valid in the study context. We set out to validate the Generalised Anxiety Disorder-7 scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9); and Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) in the most widely spoken languages in Malawi (Chichewa and Chitumbuka). We undertook translation, adaptation, and piloting to produce final versions in both languages. We conducted criterion validation of the GAD-7, PHQ-9 and PC-PTSD-5 against reference diagnoses of DSM-5 generalised anxiety disorder, major/minor depressive episode, and PTSD respectively, using the Structured Clinical Interview for DSM-5 (SCID-5). A weighted sample of screened participants had SCID interview and this was adjusted for in the analysis. We recruited convenience samples of women and men from two sites: a rural Chitumbuka-speaking site where 342 were screened and 219 had SCID; and an urban Chichewa-speaking site where 458 were screened and 251 had SCID. In both languages, the measures had acceptable internal consistency (Cronbachs alpha [&ge;] 0.75). Regarding convergent validity, PHQ-9 and GAD-7 were highly correlated but PC-PTSD-5 was only weakly/moderately correlated with the other measures. In Confirmatory Factor Analysis, best fit for GAD-7 and PC-PTSD-5 was a 1-factor structure, and for PHQ-9 was a 2-factor structure; there was only partial measurement invariance between the 2 language versions of each measure. Area under the ROC curve (AUC) for GAD-7 detection of generalised anxiety disorder was: Chitumbuka 0.759 (95%CI: 0.634, 0.871); Chichewa 0.868 (95%CI: 0.812, 0.915). AUC for PHQ-9 detection of major depression was: Chitumbuka 0.634 (95%CI: 0.441, 0.869); Chichewa 0.843 (95%CI: 0.721, 0.927). AUC for PHQ-9 detection of minor-or-major depression was: Chitumbuka 0.751 (95%CI: 0.619, 0.865); Chichewa 0.801 (95%CI: 0.714, 0.879). AUC for PC-PTSD-5 detection of PTSD was: Chitumbuka 0.682 (95%CI: 0.519, 0.853); Chichewa 0.741 (95%CI: 0.604, 0.859). In conclusion, GAD-7 and PHQ-9 showed good/acceptable validity, although criterion validity of PHQ-9 for major depression in Chitumbuka was poor. PC-PTSD-5 showed limitations to its validity, indicating need for further development of PTSD measures in Malawi.

Background. Post-stroke anxiety and depression frequently co-occur, and whether each is independently associated with cognitive impairment remains unclear because most studies model one without adjusting for the other variable. In a five-year cohort, we tested whether anxiety and depression have distinct cognitive correlates and whether early affective status predicted subsequent cognitive recovery. Methods. Patients from the STROKDEM cohort were assessed at 6, 12, 36, and 60 months post-stroke for anxiety, depression, and five cognitive domains (memory, executive functioning, attention, visuospatial functioning, and language). Two symmetric random-intercept linear mixed models regressed each affective score on the cognitive domains while adjusting for other scores. Repeated-measures correlations, multiple imputations for attrition, and exploratory trajectory and prognostic models were also used. Results. After mutual adjustment and correction, depression was independently associated with executive and visuospatial function, whereas anxiety showed no independent cognitive correlation. Repeated-measures correlation confirmed this dissociation. The anxiety findings were stable across the sensitivity analyses and multiple imputations. Attrition was selective for baseline cognition, and exploratory associations between early affect and cognitive recovery did not survive multiple imputations and were inconclusive. Limitations. Attrition was substantial and selective on baseline cognition; the persistent anxiety subgroup was small, limiting the power for trajectory analyses; and psychiatric history, psychotropic medication, and cognitive reserve beyond education were unavailable. Conclusions. The cognitive burden of post-stroke affective disorders is carried by depression, rather than anxiety. Because anxiety-related cognitive impairment largely reflects comorbid depression, screening for depression rather than anxiety alone may better identify stroke survivors at risk of cognitive impairment.

Background Multimorbidity is increasingly prevalent, and associated with worse clinical and psychosocial burdens. Interoception, the brain's ability to sense and interpret internal bodily signals, may contribute to multimorbidity, through its link with health behaviors, stress regulation, and mental health. This study examines whether self-reported interoceptive accuracy and attention is associated with multimorbidity, by identifying multimorbid subgroups and their interoceptive profiles. Methods Morbidity classes were identified through latent class analyses in two Dutch survey datasets, focusing on depression and alexithymia (DA-dataset; N = 671) and lifestyle factors (L-dataset; N = 1022). Linear regression analyses were used to assess interoceptive accuracy and attention (by the Interoceptive Accuracy Scale and Interoceptive Attention Scale respectively) among different subgroups. Results Multimorbid subgroups were characterized by older age, low socioeconomic position, and elevated physical, psychological, and behavioral problems. Multimorbid classes exhibited lower interoceptive accuracy (DA-dataset: B = -1.14, 95% CI = [-2.89, 0.62]; L-dataset: B = -2.36, 95% CI = [-3.83, -0.89]) and higher attention (DA-dataset: B = 3.62, 95% CI = [0.97, 6.27]; L-dataset: B = 1.07, 95% CI = [-1.42, 3.56]) compared to healthier classes. Conclusion Multimorbid populations demonstrated lower interoceptive accuracy and higher interoceptive attention. This highlights the psychosocial complexity of multimorbid populations which may impact their self-management and health behavior. These findings underscore the need to expand treatments to include psychosocial domains for multimorbid patients.

Background: Emotion dysregulation is a core feature of bipolar disorder (BD), yet its behavioral expression during depressive episodes, and potential differences between its types, BD-I and BD-II, remain unclear. This study used automated facial-expression analysis during naturalistic affective film viewing to examine subtype-specific and context-dependent emotional responding in bipolar depression. Methods: The sample included 135 participants: 69 healthy controls and 66 patients with BD (BD-I, 23; BD-II, 43). Participants viewed nine emotionally evocative film clips spanning negative, positive, neutral, and socially threatening contexts, while their facial expressions were continuously recorded and quantified using computer vision-based facial-expression analysis. Results: Patients with BD-I showed a distinct, context-dependent facial-expression profile, characterized by greater negative responses across multiple contexts than other groups. Specifically, they showed increased sadness during sad, reward, and amusing clips, and elevated anger during sad and neutral clips. In socially threatening contexts, BD-I participants showed a multivalent pattern of elevated anger, fear, and joy, suggesting poorly coordinated or context-incongruent affective expression. In contrast, BD-II participants did not differ significantly from healthy controls on any emotion, despite depressive symptom severity comparable to BD-I participants. Conclusions: These findings suggest that facial-expression patterns in bipolar depression differ across subtypes. BD-I may be characterized by heightened negative reactivity and altered context-appropriate modulation of emotional expression, whereas BD-II may not show comparable alterations in overt facial output. Automated facial-expression analysis during naturalistic stimulation may provide a useful behavioral marker for characterizing subtype-specific affective disturbance in bipolar depression and related psychopathology.

Background: Major depressive disorder (MDD) is a severe mental illness associated with severe clinical consequences and substantial societal burden. It's characterized by immune-inflammatory dysregulation and immune sensitization. Objective: To determine whether in vitro ketamine attenuates phytohemagglutinin (PHA)/lipopolysaccharide (LPS)-induced immune sensitization in patients with MDD and healthy controls (HCs). Methods: Whole blood from 18 patients with MDD and 18 HCs was stimulated with PHA/LPS and exposed to ketamine (0.3 M, 0.6 M, and 6 M) for 72 hours. Cytokines, chemokines, growth factors, and composite immune profiles, including M1/M2 macrophages, T helper (Th)1/2/17, the immune-inflammatory response system (IRS), and compensatory immunoregulatory system (CIRS), were synthesized and determined. Results: Under PHA and LPS stimulation in vitro, the MDD group exhibited markedly elevated immune profiles, including M1, M2, Th1, Th2, Th17, IRS, CIRS, chemokines, and growth factors, consistent with immune sensitization. Significant group-by-treatment interactions were observed for Th1-Th2, M2, growth factors, IL-12(p70), M1, and chemokines. Ketamine produced minimal changes in HCs but broader suppression in MDD, particularly at the highest concentration, without normalizing the sensitized immune phenotype. Among the immune markers with no notable group-by-treatment interactions, ketamine exerted diagnosis-independent effects, decreasing MIP-1{beta}, IL-1&{beta}, Th1, TNF-{beta} IRS, IFN-{gamma}, and IL-2 compared to the control condition. Conclusions: Ketamine exhibited two distinct immunoregulatory patterns: selective, disease-dependent attenuation of sensitized immune pathways and broader, diagnosis-independent suppression of the stimulated immune response, predominantly at higher concentrations. However, these effects were insufficient to normalize the immune-sensitized phenotype of MDD.

Accelerated 5x5 repetitive Transcranial Magnetic Stimulation (rTMS; five stimulation sessions per day for five days) is an effective treatment for Major Depressive Disorder (MDD), and has efficacy comparable to conventional once-daily rTMS. Considering the heterogeneity of symptoms in patients with MDD, it is critical to determine how accelerated 5x5 and conventional rTMS affect depression symptom domains. We compared symptom change over time in patients treated with either accelerated 5x5 rTMS (25 total sessions, n = 40) or conventional once-daily rTMS administered over six weeks (30 total sessions, n = 135). Accelerated 5x5 patients received either prolonged intermittent theta burst stimulation (piTBS) or personalized "resonant frequency" (RF) stimulation. Mixed-effects linear models were built to compare the two protocols, with the primary outcome variables being the Inventory of Depression Symptomology Self-Report (IDS), the Ruminative Response Scale (RRS), and the Profile of Mood States - Brief (POMS), yielding measures of 14 unique depression symptom domains. Both protocols led to similar improvements in all 14 depression symptom domains (all interaction term p-values > .05). Subsequent exploratory analyses demonstrated that accelerated 5x5 and conventional rTMS may differ in the time courses of their effects on anxiety, rumination, mood, depression, and vigor (p-values < .05, uncorrected). These results suggested that accelerated 5x5 rTMS has a similar efficacy in alleviating 14 depression symptom domains compared to conventional once-daily rTMS, and that either protocol may be appropriate for MDD patients with a variety of symptom profiles.

Depression and treatment-resistant depression (TRD) are significant public health issues, but the associated network-level neurobiological mechanisms remain poorly understood. This study used magnetoencephalography (MEG) to identify altered resting-state connectivity within the default mode (DMN), executive control (ECN), salience (SN), dorsal attention (DAN), motor (MN), and visual (VN) networks as potential biomarkers of depression and treatment resistance. The study recruited 168 participants (80 healthy volunteers (HVs) and 88 currently experiencing a major depressive episode (74 with TRD and 14 without TRD (noTRD))). Data Integration Analysis for Biomarker Discovery using Latent Variable Approaches for Omics Studies (DIABLO) was used to differentiate the depression, TRD, and HV subgroups and identify neural markers of depression and treatment resistance. For differentiating the depression and HV groups, the triple network model (area under the receiver operating curve (AUROC): 0.759-0.787) - which includes the DMN, ECN, and SN - outperformed the six-network model (AUROC: 0.747-0.762) across different bandwidths. For differentiating the TRD and HV groups, the triple network model demonstrated reasonable prediction across different bandwidths (AUROC: 0.737-0.807); potential within-network connectivity differences distinguished those with TRD from HVs, especially DMN within-network connectivity between the inferior parietal lobule and precuneus in the beta band (FDR-corrected p<.05). Hyperconnectivity within the SN (superior parietal lobule and frontal operculum in the alpha band) and DMN (inferior parietal lobule and lateral prefrontal cortex in the beta band) was associated with number of treatment failures (ps<.05). These findings highlight key brain regions and connectivity patterns, advancing our understanding of neural mechanisms underlying depression and treatment resistance.

Background: Medical students face significant mental health challenges, yet psychological distress and post-traumatic stress remain insufficiently characterized in lower-resource settings like Vietnam. Among potential stressors, sexual violence (SV) exposure represents a critical but understudied risk factor. This study evaluated the severity of psychological distress (PD) and post-traumatic stress symptoms (PTSS) among medical students in Northern Vietnam and examined their associations with past-year non-contact and contact SV exposure. Methods: A cross-sectional survey was conducted in May 2025 using REDCap among a probability sample of 555 medical students (years 2 to 5). Mental health outcomes were evaluated using validated instruments: the 21-item Depression, Anxiety, and Stress Scales (DASS-21) for past-week PD and the PTSD Checklist for DSM-5 (PCL-5) for past-month PTSS. Past-year non-contact and contact SV exposures were measured using the Sexual Experiences Survey-Victimization (SES-V). Multivariable linear regression modeled adjusted associations between SV exposure types and mental health symptom severity, testing for sex-specific differences. Results: Overall mental health symptom scores escalated significantly with SV exposure. Median PTSS scores increased from 11 among unexposed students to 20 for non-contact SV and 30 for contact SV (p < 0.001). Similarly, median PD scores increased from 7 (unexposed) to 11.5 (non-contact SV) and 21 (contact SV) (p < 0.001). Adjusted linear models demonstrated robust associations where both non-contact and contact SV exposure were strong independent predictors of heightened PD and PTSS severity, with no significant moderation by sex. In terms of exposure prevalence, 21.26% of students reported non-contact SV (higher in females: 26.24% vs. males: 16.12%) and 10.66% reported contact SV. Conclusions: Vietnamese medical students exposed to sexual violence experience a heavy mental health burden marked by elevated psychological distress and post-traumatic stress symptoms. To protect student mental health in lower resource settings, medical institutions must establish comprehensive trauma-informed psychological support, confidential counseling services, and targeted intervention strategies addressing both contact and non-contact stress exposures. Keywords: psychological distress, post-traumatic stress, non-contact sexual violence, contact sexual violence, university students, Vietnam

Purpose: There is a long-standing perception that individuals who stutter are less intelligent, with the disfluencies unique to stuttered speech often assumed to be the overt reflection of lower intelligence, despite no supporting evidence. The purpose of the present study was to explore the validity of this assumption by examining the cognitive abilities of adults who stutter compared to the general population using the NIH Toolbox (C) Cognition Battery (NIHTB-CB). Method: Sixty-three adults who stutter completed the NIHTB-CB, which includes seven standardized measures assessing crystallized cognition (Picture Vocabulary, Oral Reading) and fluid cognition (List Sorting Memory Test, Pattern Comparison Processing Speed Test, Flanker Inhibitory Control Test, Dimensional Change Card Sort Test, Picture Sequence Memory Test). The NIHTB-CB generates t-scores adjusted for demographic variables based on a large sample of neurotypical adults. Results: Composite scores of overall cognition for adults who stutter were not statistically equivalent, rather, their scores were higher than the general population. Higher scores were driven by crystallized cognition, with significantly higher scores on Oral Reading subscale. Conclusions: Present findings demonstrate that adults who stutter possess cognitive skills that are comparable to or potentially higher, than the general population. These results challenge the misconception that stuttering reflects diminished intelligence and offer evidence to mitigate stereotype threat.

Aim: The Patient Safety Screener-3 (PSS-3) is a brief suicide-risk screening tool. Item 1 of this scale assesses depressive mood but is not included in the total score. We examined the association of item 1 with depressive symptom severity and characterized the suicide-related risk captured by PSS-3 total positivity. Methods: We conducted a nationwide cross-sectional survey among resident physicians in Japan. Associations between PSS-3 item 1 endorsement and Patient Health Questionnaire-9 (PHQ-9) scores were evaluated using the Wilcoxon rank-sum test. Diagnostic performance of item 1 was evaluated using PHQ-9 positivity ([&ge;]10) as reference standard. We also compared Short-form Scale for Suicide Ideation (SIS-6) scores according to PSS-3 total positivity and PHQ-9 item 9 positivity. Results: A total of 1,844 participants were included. PSS-3 item 1 was endorsed by 443 physicians (24.0%), and 47 (2.5%) met the criteria for PSS-3 total positivity. Item 1 showed 79.3% sensitivity and 79.5% specificity for PHQ-9 positivity. SIS-6 scores were higher in the PSS-3 total-positive group than in the total-negative group (median [IQR], 6 [5-9] vs 0 [0-1]; p<0.001). The SIS-6 showed a higher area under the receiver operating characteristic curve (AUC) and Youden index using PSS-3 total positivity (AUC, 0.961; optimal cutoff, 3) than PHQ-9 item 9 positivity (AUC, 0.907; optimal cutoff, 2). Discussion: PSS-3 may support brief, simultaneous screening for depressive symptoms and suicide-related risk. Compared with PHQ-9 item 9, PSS-3 may capture a more severe spectrum of suicide-related risk. PSS-3 may facilitate identification of individuals requiring further mental health assessment.

Purpose. Perinatal loss is associated with a high risk of persistent psychological distress, including prolonged grief, depression, anxiety, and post-traumatic stress symptoms. Cognitive processes such as rumination may play a crucial role in maintaining and amplifying distress following loss, yet their specific contribution in perinatal bereavement remains underexplored. Methods. The CARING (Cognitive Analysis and Rumination INvestigation in perinatal Grief) study employed a cross-sectional design involving 298 parents who experienced perinatal loss within the previous five years. Participants completed an anonymous online survey including measures of depressive rumination (Ruminative Response Scale, RRS), angry rumination (Anger Rumination Scale, ARS), perinatal grief (Perinatal Grief Scale, PGS), general psychopathology (SCL-90), and post-traumatic stress symptoms (NSESSS). Non-parametric analyses were conducted to examine associations between rumination patterns and psychological outcomes. Results. Higher levels of rumination were significantly associated with greater perinatal grief, depressive and anxiety symptoms, and post-traumatic stress. Depressive rumination showed consistently stronger associations with all outcomes compared to angry rumination. Participants presenting both depressive and angry rumination exhibited the highest levels of grief intensity, psychological distress, and PTSD symptoms, suggesting a graded relationship between rumination patterns and severity of distress. Rumination levels were not significantly associated with gestational age at loss or with having received psychological support. Conclusions. Rumination, particularly in its depressive form, appears to function as a transdiagnostic cognitive vulnerability factor in perinatal bereavement. These findings highlight rumination as a potential target for early screening and tailored psychological interventions aimed at reducing long-term distress following perinatal loss.

Introduction: Functional Neurological Disorder (FND) affects women approximately three times more often than men. This disparity has largely been attributed to higher trauma prevalence and diagnostic bias, while the potential contribution of hormonal influences has received little attention. Methods: An online questionnaire was distributed through FND clinics in thirteen countries, assessing self-reported symptom change across five hormonal events: hormonal contraception, pregnancy, the menstrual cycle, menopause, and gender-affirming hormone therapy. Eligible participants were cisgender women with a diagnosis of FND, or gender minority individuals (transgender or non-binary). Perceived symptom change was rated on a five-point scale ranging from large improvement to large worsening. Results: Among 262 respondents (96% female; mean age 39 years), several hormonal contexts were associated with self-reported symptom changes. Overall, hormonal contraception and pregnancy were frequently associated with worsening of motor and cognitive symptoms, and menopause with worsening across all symptom domains. Menstrual cycle analysis revealed a phase-dependent pattern: worsening was most frequently reported during menstruation and the luteal phase, whereas improvement was most frequent during the follicular phase. Reported changes were not uniform, with a substantial proportion of participants describing no change or improvement. Conclusion: Self-reported FND symptom severity appears to vary with hormonal context, with motor and cognitive symptoms most consistently affected. Given the retrospective, self-report design, these findings are hypothesis-generating and support prospective research into the role of hormonal transitions in FND.

Cognitive deficits in depression often persist despite pharmacological and psychotherapeutic treatment. Existing cognitive retraining programs are typically time- and resource-intensive, and place limited emphasis on addressing subjectively perceived cognitive difficulties or generalization of gains. This proof-of-concept study aimed to adapt the Integrated Cognitive Control Training (ICCT) into a brief format for patients with depression and to generate preliminary evidence of feasibility and effectiveness. The intervention was adapted into a manualized five-session program through a literature review, expert surveys involving clinicians and individuals with lived experience of depression, and a trial run. The study followed a single-group, open-label pre-post design (N = 16). Significant improvements were observed in cognitive flexibility (Color Trails Test-2: t = 3.52, p = 0.003, d = 0.88), depression severity (Montgomery-[A]sberg Depression Rating Scale: t = 6.66, p < 0.001, d = 1.67), and subjective cognition (Perceived Deficits Questionnaire: t = 5.06, p < 0.001, d = 1.3). The intervention demonstrated high acceptability and demand. These findings suggest that the Brief ICCT is a feasible and potentially effective approach for addressing cognitive deficits, with improvements extending to depressive symptom severity and socio-occupational functioning. These proof-of-concept findings justify further evaluation of Brief ICCT in adequately powered randomized controlled trials.

Background: Adolescent major depressive disorder (MDD) is heterogeneous, with diverse and frequently co-occurring psychopathological manifestations. Although family-related experiences, childhood trauma, rumination, and psychological resilience have each been linked to adolescent mental health, less is known about how they are interrelated and jointly associated with distinct psychopathological domains. This study examined these associations within an integrative framework. Methods: This cross-sectional study included 80 adolescents with MDD and 53 healthy controls. Family functioning, parenting, childhood trauma, rumination, psychological resilience, and four clinical domains, including affective distress, suicidal ideation, the non-suicidal self-injury (NSSI) spectrum, and self-regulation difficulties, were assessed using validated instruments. Partial least squares structural equation modeling (PLS-SEM) examined their multivariate associations. Sensitivity analyses restricted to the MDD sample and covariate-adjusted regression models assessed the robustness of the findings. Results: The four clinical domains showed high reliability and acceptable discriminant validity. Family dysfunction was associated with maladaptive parenting and childhood trauma, and maladaptive parenting was associated with childhood trauma (beta = .383-.600; all p < .001). Childhood trauma was associated with greater rumination (beta = .625) and lower psychological resilience (beta = -.405; both p < .001). Rumination and psychological resilience showed opposing associations with all four domains (rumination: beta = .280-.559; resilience: beta = -.265 to -.399; all p <= .006). Family dysfunction, maladaptive parenting, and childhood trauma showed significant total indirect associations with each domain (all p < .001). The model explained 53%-85% of the variance across the four domains. The MDD-only analysis reproduced the principal associations observed in the combined sample and additionally showed direct associations between maladaptive parenting and all four clinical domains. Covariate-adjusted analyses retained all principal associations except the resilience-NSSI association. Conclusions: The findings support a multidimensional characterization of adolescent MDD comprising distinguishable yet interrelated domains of affective-psychosomatic distress, suicidal ideation, the NSSI spectrum, and self-regulation difficulties. The partly shared and partly distinct associations of these domains with family-related adversity, rumination, and psychological resilience support considering domain-level psychopathology alongside diagnostic status and global depression severity in research on adolescent MDD.

Background: Management of markedly treatment-resistant depression is characterized by low initial benefit and poor durability. Treatments with sustained benefits are needed. This report summarizes clinical outcomes and durability of both the active treatment arm (Early-Active) and the initially sham treatment arm (Delayed-Active) over the second and third years of the multicenter, prospective, implanted vagus nerve stimulation (VNS) RECOVER trial. Methods: A total of 436 participants (N=221 Early-Active and N=215 Delayed-Active, 65.8% females) were studied. Within each group, analyses of change in benefit (depressive symptoms, clinical impression, quality of life [QoL], daily function, and a composite measure) occurred with assessments at 12, 18, 24, 30, and 36 months. Two within-group methods of benefit appraisal over time were conducted: 1) a comparison of the degree of benefit change, and 2) a comparison of proportions of participants achieving benefit categories. Additionally, the degree of durability of benefit was assessed, comparing 12-24 months, 24-36 months, and 12-36 months. Results: For the Early-Active group: The 12-24-month and 12-36-month periods, but not the 24-36-month period, demonstrated significant improvement in benefit categories for depressive symptoms and clinical impression measures. Similarly, statistically significant increases in the proportions of participants achieving benefit during Year 2 for depressive and clinical impression measures occurred. For the Delayed-Active group: The 12-24-month (first exposure of this group to active VNS) and 12-36-month periods, but not the 24-36-month period, demonstrated statistically significant improvements in benefit categories for depressive symptoms and clinical impression measures. Additionally, statistically significant increases in the proportions of participants achieving benefit during Year 2 for depressive symptoms, clinical impression, QoL, daily function, and the composite measure were observed. Averaged across the depressive symptom and clinical impression measures, the Early-Active group demonstrated continued progression to higher benefit categories during Years 2 and 3, whereas the Delayed-Active group was characterized by the emergence of new benefit during Year 2 followed by further progression to higher benefit categories during Year 3. Durability: Robust durability of response was observed for both groups across all time intervals, with a median of 71.1% and 69.0% maintaining or improving benefit from 12 to 36 months for Early-Active and Delayed-Active, respectively. Conclusions: In a highly chronic and markedly resistant depressed sample, active VNS produced benefits that often emerged gradually, sometimes beyond one year after initiation, continued to improve in degree of benefit over time, and were highly durable. The time-associated benefit patterns observed in the sham group (Delayed-Active) closely resembled those of the initially active group (Early-Active) but were delayed by approximately one year, consistent with the delay in therapy activation.

Major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are prevalent, chronic, and disabling mental health conditions which are difficult to treat. Ketamine has demonstrated effect for improving depression and PTSD symptoms independently but reports often overlook focused comorbid improvement of these symptoms within individuals. To address this, we assessed blood-based biomarker and psychological changes following low-dose oral ketamine treatment for adults with MDD alone (n=14) and comorbid MDD+PTSD (n=21). Before treatment, the MDD clinical group presented with more severe depression, lower serotonin levels and higher kynurenine levels than the MDD+PTSD group. Post-treatment there were no detectable differences in the biological response between clinical groups, with combined analysis revealing common decreases in circulating brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF-A). Additionally, post-treatment, both clinical groups showed improvements in anxiety, stress, social functioning, suicidal ideation, and general well-being measures, as well as individual improvements in depression scores and PTSD symptoms in the MDD- and PTSD-containing groups, respectively. Collectively, this study presents additional evidence that low-dose oral ketamine treatment can be effective for MDD and MDD+PTSD, individually and comorbidly, and that both MDD and PTSD clinical groups responded in the same biological manner.

Purpose This study aimed to examine the association between screen time and depressive symptoms among Chinese college students, and to investigate the mediating roles of sleep quality and emotion regulation in this relationship. Furthermore, a serial mediation model was constructed to elucidate the underlying psychological mechanisms linking screen exposure to depression. Methods A stratified cluster sampling method was employed to recruit 10,999 college students for a cross-sectional questionnaire survey. Data were collected on screen time, sleep quality, emotion regulation ability, and depressive symptoms. Descriptive statistics, correlation analyses, and regression analyses were conducted using SPSS 26.0 A serial mediation model was tested using the PROCESS macro (Model 6), and bootstrapping procedures were applied to estimate the significance of indirect effects. Results Correlation analyses indicated that screen time was significantly positively associated with depressive symptoms (r = 0.16, p < 0.01) and sleep quality (r = 0.15, p < 0.01), and significantly negatively associated with emotion regulation (r = -0.13, p < 0.01). Sleep quality was positively correlated with depressive symptoms (r = 0.31, p < 0.01), whereas emotion regulation was negatively correlated with depressive symptoms (r = -0.42, p < 0.01). Regression analyses further showed that screen time significantly positively predicted depressive symptoms ({beta} = 0.712, p < 0.001), positively predicted sleep quality ({beta} = 0.217, p < 0.001), and negatively predicted emotion regulation ({beta} = -0.085, p < 0.001). In addition, both sleep quality ({beta} = 1.318, p < 0.001) and emotion regulation ({beta} = -0.424, p < 0.001) were significant predictors of depressive symptoms. Mediation analyses demonstrated that sleep quality significantly mediated the association between screen time and depressive symptoms (95% CI [0.239, 0.332]), as did emotion regulation (95% CI [0.269, 0.416]). Moreover, a significant serial mediation effect of sleep quality and emotion regulation was observed in the relationship between screen time and depressive symptoms (95% CI [0.082, 0.117]). Conclusion Screen time is significantly associated with depressive symptoms among college students, with sleep quality and emotion regulation serving as important mediating mechanisms. Extended screen exposure may be linked to higher levels of depressive symptoms by impairing sleep quality and weakening emotion regulation capacity.