
BACKGROUND:Anxiety disorders are the most frequent mental disorders worldwide. Although exposure therapy is the gold-standard treatment for anxiety disorders, almost half of patients fail to achieve sufficient improvements. While much has been learned about for whom psychotherapy works and why, far less is understood about when it works. Emerging evidence indicates that estradiol and progesterone may affect fear extinction, yet studies examining the effects of menstrual cycle phase on exposure therapy outcomes remain lacking. This study is the first to investigate to what extent biologically informed menstrual cycle phase affects exposure therapy outcomes in women with spider phobia. METHOD:N=45 women with spider phobia in 1) the early to mid-follicular phase, 2) the mid-luteal phase, or 3) using hormonal contraceptives (HC), participated in a group-based exposure therapy. Symptoms were assessed at baseline, one-week post-therapy, and at 12-14 weeks follow-up, using the Spider Phobia Questionnaire (SPQ), the Fear of Spiders Questionnaire (FSQ), and a behavioral approach test (BAT). RESULTS:Both phobic fear and avoidance behavior improved significantly over time. Although improvement did not differ between menstrual cycle groups, higher progesterone levels on the day of exposure therapy were associated with less improvement in behavioral avoidance. CONCLUSION:The present findings provide preliminary evidence that ovarian hormones on the day of exposure therapy may affect exposure-based outcomes, particularly reductions in behavioral avoidance. More research in larger samples is needed to further investigate menstrual cycle phase effects in exposure-based treatment. If replicated, the findings would attest to the potential of bio-rhythm informed psychotherapy.
Major depressive disorder (MDD) is a prevalent and disabling condition, yet predicting individual response to antidepressants remains difficult. Traditional symptom-based assessments, typically conducted weeks apart, may miss early and dynamic changes. Daily self-reported measures of wellbeing dimensions, particularly via simple tools such as visual analog scales (VAS), could provide ecologically valid and patient-centered markers of early treatment response. This study aimed to identify distinct early trajectories of self-rated health during antidepressant initiation and examine their associations with baseline clinical characteristics and outcomes at 6-8 weeks. In this multicentre naturalistic study, 1536 outpatients with MDD initiating agomelatine monotherapy were recruited across 388 community psychiatry centers. The primary outcome was daily self-rated health during the first 14 days, assessed using the EuroQol VAS. Latent class analysis identified distinct trajectories of self-rated health evolution, with model selection based on Akaike and Bayesian information criteria (AIC/BIC), entropy, and clinical interpretability. A five-class solution was retained, including persistently high or low trajectories, stable intermediate patterns, and one subgroup showing marked early improvement despite low baseline values. Trajectories were associated with baseline clinical severity and different symptomatic and functional outcomes at 6-8 weeks. Patients with rapid early improvement had the highest remission rates, whereas those with severe baseline symptoms and limited early improvement had the poorest outcomes. These findings support the clinical utility of early wellbeing trajectories for personalized monitoring during antidepressant treatment.
INTRODUCTION:Approximately 30-40% of patients with major depressive disorder fail to respond to conventional antidepressants. Ketamine and esketamine are increasingly used, yet synthesized data on cumulative safety remain limited. This systematic review evaluated long-term safety of both agents. METHODS:MEDLINE, PsycINFO, Embase, and Cochrane Library were searched from inception through January 29, 2026. Eligible studies enrolled adults with depressive disorders receiving ketamine or esketamine with ≥12-week follow-up. Safety outcomes were synthesized narratively across nine domains: neurocognitive, dissociative/psychotomimetic, sedation, cardiovascular, hepatic, urinary, misuse/dependence, suicidality, and serious adverse events (SAEs). Risk of bias was assessed. RESULTS:Thirty-two studies (11 RCTs, 21 non-randomized) met inclusion criteria, with follow-up ranging from 3 months to 9 years. Across cardiovascular, hepatic, and urinary domains, neither racemic ketamine nor intranasal esketamine demonstrated evidence of cumulative organ toxicity during maintenance treatment. Dissociative and sedative effects were common but consistently transient, resolving within 1-2 hours of administration. No treatment-emergent neurocognitive dysfunction was identified; urologic complications were rare and resolved with treatment discontinuation. No cases of iatrogenic addiction, drug-seeking, or withdrawal were documented for either formulation. Suicidal ideation scores showed reductions from baseline, though suicide attempts and completions occurred during follow-up periods. SAEs attributable to treatment were rare. The comparative analyses suggested essentially equivalent long-term safety profiles between racemic ketamine and intranasal esketamine. CONCLUSION:Current evidence supports the safety of ketamine and esketamine for TRD, with no cumulative organ toxicity or iatrogenic addiction during maintenance treatment. Acute effects remain transient and manageable. However, findings are limited by heterogeneity in safety monitoring across studies.
INTRODUCTION:Psychopathology research typically relies on nomothetic (group-level) data to infer idiographic (person-level) processes, limiting clinical relevance, and failing to capture complex individual presentations. Conversely, idiographic approaches capture within-person dynamics but often lack theoretical structure to support generalization, creating a nomothetic-idiographic gap. This study addresses this gap by operationalising Ehlers and Clark's (E&C) Cognitive Model of Posttraumatic Stress Disorder (PTSD) within a theory-guided idiographic network framework. METHODS:Study 1 used simulations to establish data requirements for reliably testing model-derived hypotheses. Study 2 applied this framework to intensive longitudinal data from trauma-exposed individuals. Fifty-five participants (31 with PTSD, 24 with clinical-level symptoms) selected personalized items reflecting core model components: negative appraisals, trauma memory, triggers, sense of current threat, and maladaptive strategies. A subsample of 41 participants completed 3 weeks of Ecological Momentary Assessment, yielding 2,594 observations (M = 63.2 per participant). Individualized items were mapped onto shared theoretical constructs and analyzed using complementary network models. RESULTS:Findings provided empirical support for key assumptions of the E&C model, particularly the central role of sense of current threat and its associations with trauma memory, negative appraisals, triggers, and maladaptive strategies. Clustering of individual networks identified four recurring formulation subtypes characterized by threat reactivity, appraisal centrality, memory centrality, or trigger-threat association. CONCLUSION:We demonstrate a method for bridging individualized assessment with theory-driven analysis. By combining personalized data collection with a shared mechanistic framework, idiographic networks can extend beyond single-case descriptions to identify common clinical patterns, with potential implications for formulation, intervention planning, and evaluation.
BACKGROUND:The Anorexia Nervosa Treatment of OutPatients (ANTOP) randomized controlled trial (RCT) involved 242 adult patients with anorexia nervosa. Patients from 10 German university hospitals were randomly allocated to 10 months of treatment with focal psychodynamic therapy (FPT), enhanced cognitive behaviour therapy (CBT-E), or optimized treatment as usual (TAU-O). At the end of treatment and follow-up no significant BMI differences between groups were reported. The present study is an explorative, secondary analysis of moderators of weight gain for FPT and CBT-E. METHODS:N=160 patients - randomized to FPT and CBT-E - were included in the analysis. Moderator analysis was conducted by using a mixed model approach for repeated measures (MMRM). The outcome variable was BMI at the last follow-up T5 (mean time of 5·96 years after the beginning of the study). RESULTS:Low depression severity and high mental quality of life (QoL) at baseline moderated the outcome in favour of CBT-E, whereas high depression severity and low mental QoL was associated with a better outcome in FPT. Sensitivity analyses to predict BMI at earlier time points T1-T4 produced the same results. The direction of the moderator effects was the same for CBT-E and FPT across all time points. Graphical visualisation confirms that there is a wide range where both treatments perform similarly, while CBT or FPT perform differently in the extreme ranges of these two variables. INTERPRETATION:These findings suggest that baseline psychological burden may inform the selection of psychotherapy modality in anorexia nervosa, supporting a move toward personalized, mechanism-informed treatment allocation.
Psychiatric comorbidity affects at least one-third of patients hospitalized on medical-surgical services, with over half facing psychosocial stressors that impact care. These comorbidities are associated with poorer outcomes, including prolonged hospitalization, higher costs, increased restraint use, and readmission risk. However, the role of social determinants of health (SDoH) in shaping these outcomes remains insufficiently characterized. This scoping review examined how SDoH influence psychiatric comorbidity and clinical outcomes in medical-surgical inpatient settings. On February 6, 2024, a systematic search was conducted across Ovid MEDLINE, Embase, PsychINFO, Web of Science, and Cochrane databases. Of 5,372 articles screened, 77 met inclusion criteria. The 48 articles published since 2003 (the year Consultation-Liaison Psychiatry was first accredited as a subspecialty in the U.S.) were synthesized for contemporary relevance. Most were retrospective observational (37.5%) or cross-sectional studies (31.2%), with global representation across North America, Europe, Asia, and other regions. Commonly reported demographic factors and SDoH included age, sex, ethnicity, marital status, housing, and socioeconomic status. Psychiatric diagnoses were associated with social disadvantage and were frequently linked to longer length of stay. Factors like food insecurity, neighborhood disadvantage, and incarceration were underexplored. Few studies assessed proactive or interventional care. Findings highlight the need for longitudinal and interventional research to clarify the complex interrelationships among SDoH, psychiatric conditions, medical comorbidity, and hospital outcomes to inform equitable models of care.
INTRODUCTION:It remains contested if rapid onset of affective symptoms during antidepressant tapering reflects pharmacological withdrawal effects or relapse of an underlying mental disorder. METHODS:A prospective cohort (n=32) of adult primary care patients from Switzerland was assessed repeatedly over 26 weeks after initiation of antidepressant tapering. Dose reductions and within-person change in withdrawal symptoms (DESS affective and discriminatory physical symptom subscales), depressive (PHQ-9) and anxiety symptoms (GAD-7) were assessed over six intervals, resulting in 187 measurements for each variable. RESULTS:Over the 26-week observation period, within-person change in PHQ-9 and GAD-7 scores were strongly associated with concurrent change in DESS affective scores (r≈0.6), and both were also moderately associated with DESS physical scores (r≈0.3). Dose reductions were accompanied by significant increases in DESS affective, PHQ-9 and GAD-7, while scores in both DESS affective and GAD-7 significantly declined during intervals without dose reductions. Within-person change in DESS physical score was independently associated with changes in DESS affective and both PHQ-9 and GAD-7 scores. Adjusting for DESS physical scores substantially attenuated the within-person increase in DESS affective, PHQ-9 and GAD-7 scores during periods with dose reductions. CONCLUSION:During antidepressant tapering, affective symptoms reflect a periodic course of increasing intensity after dose reductions and decreasing intensity after stabilizations of dosage that is accompanied by change in discriminatory physical withdrawal symptoms. Although causality cannot be inferred, this pattern indicates withdrawal reactions rather than relapse of mental disorders. These findings are relevant for researchers evaluating discontinuation trials and clinicians seeing patients during antidepressant tapering.
INTRODUCTION:The high prevalence of psychological distress and shortage of mental health professionals create a service gap for highly symptomatic populations exceeding routine care capacity. We evaluated a hybrid digital mindfulness intervention (MIED) delivered via a train-the-trainer (TTT) model for reducing psychological distress and providing economic value. METHODS:In this randomized controlled trial in China, adults with significant psychological distress (Kessler-10 score ≥ 22) were assigned (1:1) to 8-week MIED plus services as usual (SAU), or SAU alone. Primary outcomes were 8-week trajectory of psychological distress. Secondary outcomes included mental health indicators and short-term cost-utility. Intention-to-treat analyses used generalized estimating equations (GEE). RESULTS:Between Nov 1 and 8, 2024, 1,281 participants were assigned (MIED: n = 641; SAU: n = 640). GEE revealed a significant Group × Time interaction for distress (χ² (4) = 143.611, p < 0.001), with the intervention group demonstrating greater reductions than SAU (Cohen's d = -0.526 at Week 8). Secondary indicators also improved (p < 0.001). From a societal perspective, MIED incurred lower mean costs (993 CNY [~$140] vs 1,326 CNY [~$186]; p < 0.001) with 95% probability of cost-effectiveness at 9,246 CNY [~$1,299] per quality-adjusted life-year. Adherence was high (mean, 6.04 of 8 sessions). No severe adverse events were identified, and self-reported meditation-related adverse experiences declined over time within the intervention group. CONCLUSIONS:Compared with SAU, TTT-delivered MIED is a safe, effective, and potentially cost-saving adjunct strategy for scaling mindfulness interventions in resource-constrained systems. Future research should evaluate long-term sustainability beyond 8 weeks.
Procrastination is highly prevalent among university students and associated with substantial impairments in well-being and functioning. This randomized controlled trial examined the efficacy of two single-session interventions (SSIs) - one based on Cognitive Behavioural Therapy (CBT) and one on Acceptance and Commitment Therapy (ACT) - for reducing procrastination and tested the role of outcome expectations and experimentally induced expectation (in)congruence. A total of 151 students with recurrent procrastination and a currently postponed task were randomly assigned to a CBT-SSI, ACT-SSI, or a no-intervention control group. Interventions (approximately 60 minutes) were delivered face-to-face and preceded by a videotaped ACT- or CBT-based treatment rationale to manipulate expectation congruence. Assessments took place at baseline, post-intervention, and 2-week follow-up. The primary outcome was state procrastination (APSI-d); secondary outcomes included APSI-d Anxiety and Doubt and Task Aversion, depressive symptoms (PHQ-9), psychological flexibility (CompACT-8), perceived improvement and improvement expectations (G-EEE). Linear mixed models showed a substantial time x condition interaction for state procrastination, with both SSIs yielding significantly greater reductions than the control group and no significant difference between CBT and ACT. Similar patterns emerged for task-related anxiety and doubt, depressive symptoms, psychological flexibility (small-to-moderate gains), and perceived improvement. Higher baseline improvement expectations were associated with greater improvement, whereas expectation congruence and experimentally induced expectation violation did not differentially affect expectations or outcomes. Findings suggest that CBT- and ACT-based SSIs are effective, low-threshold options for reducing procrastination in students in the short term and highlight adherence and treatment expectations as important levers for optimizing brief interventions.
Background Cognitive Behaviour Therapy for psychosis (CBTp) is recommended for treating psychosis. However, access to CBTp is extremely poor for patients internationally due to its intensive nature and delivery by highly trained therapists. This study evaluated the clinical and cost effectiveness of the GiVE intervention (Guided self-help CBT for distressing voices) delivered by briefly trained therapists (Assistant Psychologists). Methods This study was a pragmatic, two-arm, parallel group, superiority randomised controlled trial, comparing the GiVE intervention (delivered by Assistant Psychologists) in addition to treatment-as-usual (TAU) to TAU alone, recruiting patients with psychosis across three National Health Service sites in the UK, using 1:1 allocation and blinded post-treatment and follow-up assessments. Clinical and health economic outcomes were assessed at baseline, 16 weeks, and 28 weeks. The primary outcome was the Psychotic Symptom Rating Scale - Auditory Hallucinations Distress Scale (PSYRATS-AH Distress). Results In total, 135 participants were randomised: 68 to GiVE plus TAU, 67 to TAU alone. Participant's mean age was 43.8 years (SD=12.1; range 18-69), 44 (33%) were women, 88 (65%) men, and 2 (1%) non-binary. For the intention-to-treat analysis, adjusted between-group differences in mean PSYRATS-AH Distress were -0·73 (95% CI -2·34 to 0·88; p=0·376; Cohen's d=-0·35) at 16-weeks and -0·61 (95% CI -2·23 to 1·01; p=0·460; Cohen's d=-0·30) at 28-weeks in favour of GiVE plus TAU but were not statistically significant. Conclusion Our study found that the GiVE intervention was not clinically effective in treating distressing voice hearing experiences when delivered by briefly trained Assistant Psychologists to psychosis patients.
Background: Millions of people use language models to discuss mental health concerns, including suicidal ideation, but limited frameworks exist for evaluating whether these systems respond safely. Benchmarking, the practice of administering standardized assessments to language models, offers direct parallels to clinical competency evaluation, yet few clinicians are involved in designing, validating, or interpreting these assessments. Aims: To introduce mental health professionals to benchmarking language models by administering a validated clinical instrument and demonstrating how configuration decisions, measurement limitations, and scoring context affect result interpretation. Method: We administered the Suicide Intervention Response Inventory (SIRI-2) programmatically to nine commercially available language models from three providers. Each item was presented 60 times per model (three prompt variants × two temperature settings x 10 repetitions), yielding 27,000 individually scored responses compared against point-in-time expert consensus. Results: Total scores ranged from 19.5 to 84.0 (expert panel baseline: 32.5). Prompt design alone shifted individual model scores by as much as the difference between trained and untrained human groups. The best performing model approached the instrument’s measurement floor. All nine models consistently overrated clinically inappropriate responses that sounded supportive. Conclusions: A single benchmark score can support markedly different claims depending on the assumed standard of clinical behavior, the instrument's remaining measurement range, and the configuration that produced the result. The skills required to make these distinctions must become core competencies. Benchmark results are increasingly utilized to support claims about mental health safety that may not be accurate, making it necessary to close the gap between clinical measurement and AI.
INTRODUCTION:Comorbidity between schizophrenia (SCZ) and chronic diseases is well documented. However, it remains unknown whether unaffected individuals with elevated SCZ genetic liability also face increased risk, and what biological pathways may underlie these associations. METHODS:We analyzed 426,237 UK Biobank participants without SCZ to test associations between SCZ polygenic risk score (SCZ-PRS) and 24 chronic diseases using logistic regression. Multi-omics mediation analysis incorporated seven inflammatory markers, 1,463 plasma proteins, and 250 circulating metabolites to delineate intermediate pathways linking genetic liability to disease outcomes. Genetic colocalization analyses were further conducted to determine whether SCZ genetic liability and chronic diseases share common association signals at the locus level. RESULTS:Higher SCZ-PRS was associated with increased risk of asthma (odds ratio [OR] = 1.018, 95% confidence interval [CI]: 1.008-1.029), chronic obstructive pulmonary disease (1.033, 1.017-1.050), liver disease (1.033, 1.015-1.051), peptic ulcer (1.032, 1.013-1.051), and fluid/electrolyte disorders (1.027, 1.014-1.040), while conferring reduced risk of diabetes (0.979, 0.968-0.991) and renal disease (0.978, 0.964-0.992). Multi-omics mediation revealed that these bidirectional associations were linked to immune cell activity (notably eosinophils, neutrophils, and monocytes), lipid and energy metabolism (lipoprotein composition, fatty-acid unsaturation, creatinine, lactate), and immune-regulatory proteins (e.g., HLA-E, CD1C, SPINT1). Shared genetic signals, notably at HLA and SLC39A8, reinforced these immune-metabolic pathways. CONCLUSIONS:SCZ-PRS is associated with multiple chronic diseases among unaffected individuals, and these associations suggest shared biological pathways. These findings support a psycho-neuro-immune-metabolic interpretation of SCZ-related chronic physical comorbidity and a more integrated psychosomatic understanding of the shared biology linking psychiatric vulnerability with chronic physical disease.
Childhood maltreatment is a major risk factor for depression and may contribute to sex differences in depression prevalence. We examined sex-specific associations between childhood maltreatment and depression and estimated the proportion of depression cases attributable to maltreatment subtypes. We analyzed baseline data from 159,045 participants (49.4% female; aged 19-72) in the German National Cohort (NAKO). Childhood maltreatment was assessed via the Childhood Trauma Screener; depression via self-reported physician's diagnosis and MINI classification (lifetime) and the PHQ-9 (current). Associations, including sex interactions, were modeled using binary logistic regressions. Disparity decomposition and sex-stratified population attributable fractions quantified the contribution of childhood maltreatment to depression. Childhood maltreatment was associated with increased odds of lifetime (ORphysician's diagnosis=2.45 [2.38,2.53]; ORMINI=2.30 [2.18,2.43]) and current depression (OR=2.90 [2.79,3.02], all padj<0.001). Sex interactions were observed for physician's diagnosis: physical abuse (padj=0.024) and neglect (padj<0.001) had stronger associations in females (ORphysical abuse=2.74 [2.59,2.90]; ORphysical neglect=1.36 [1.28,1.44]) than males (ORphysical abuse=2.36 [2.21,2.52]; ORphysical neglect=1.08 [1.00,1.16]), whereas sexual abuse (padj=0.003) showed stronger associations in males (OR=3.23 [2.91,3.57]) than females (OR=2.61 [2.48,2.75]). Overall, childhood maltreatment accounted for 21.2-26.2% of lifetime and 33.4% of current depression. Population attributable fractions were higher in females than males for lifetime (24.5-28.5% vs. 16.0-20.9%) and current depression (36.1% vs. 28.4%). Emotional subtypes contributed the highest population attributable fractions (up to 10.2%). Childhood maltreatment contributed 19.2-22.4% to the association between sex and depression. Childhood maltreatment accounts for a substantial proportion of depression in both sexes, with stronger overall associations in females. Sex-specific prevention may help reduce depression prevalence.
INTRODUCTION:Social functioning is a key component of recovery in depression, yet most research on first-line treatments focuses on symptom reduction, and comparative evidence on social functioning is limited. We aimed to evaluate the comparative effects of psychotherapy, antidepressant medication, and their combination on social functioning in adults with major depression. METHODS:We conducted a systematic review and network meta-analysis of randomized controlled trials up to May 1, 2025. Eligible trials compared psychotherapy, antidepressant medication, combined treatment, and control conditions (placebo, care as usual, waitlist, or no/minimal treatment) in adults with major depression. Effects were calculated as standardized mean differences (SMDs) in social functioning instruments (e.g., Sheehan Disability Scale) at posttreatment (mean 12 weeks) and follow-up (mean 32 weeks). Random effects models were used. We assessed risk of bias and conducted sensitivity analyses. Certainty of evidence was evaluated using CINeMA. RESULTS:Of 490 identified trials, 94 (19%; 23,874 participants) reported social functioning and were included. All active treatments outperformed control conditions. Effects varied substantially by control condition type, with waitlist comparisons yielding the largest estimates and comparisons against placebo or care as usual yielding more conservative effects. Combined psychotherapy and pharmacotherapy showed the largest effects versus placebo at posttreatment (SMD 0.75, 95% CI: 0.57-0.94) and follow-up (1.08, 0.62-1.54). Psychotherapy and pharmacotherapy did not differ at posttreatment (SMD 0.10, 95% CI: -0.05 to 0.25) or follow-up (0.27, 95% CI: 0.00-0.54). Certainty of the evidence ranged from moderate to low. CONCLUSION:First-line depression treatments support not only symptom reduction but also meaningful participation in daily life. However, only one-fifth of trials assessed this outcome, highlighting the need to better integrate patient-valued outcomes into future trials.
INTRODUCTION:Ketamine combined with psychotherapy has shown promise in treating posttraumatic stress disorder (PTSD), but predictors of clinical benefit remain unclear. In this systematic review and individual participant data meta-analysis (IPDMA), we examined patient- and treatment-level predictors of PTSD symptom change after combined treatment. METHODS:Eligible studies combined ketamine with psychotherapy in adults with PTSD. The primary outcome was PTSD symptom change on the PTSD Checklist for DSM-5 (PCL-5). We fit linear mixed-effects models with a random intercept for study and fixed effects for age, sex, baseline PCL-5, number of ketamine sessions, number of psychotherapy sessions, administration route, and treatment duration. Sex-stratified analyses and a quality-restricted sensitivity analysis were conducted. RESULTS:Twelve studies (533 participants) were included; nine were of poor quality. Greater improvement was associated with more psychotherapy (β = 1.03 per session) and more ketamine sessions (β = 1.15 per session), higher baseline symptom severity (β = 0.50 per PCL-5 point), and shorter treatment duration (β = -0.58 per week). Between-study heterogeneity was nontrivial (intraclass correlation coefficient ≈ 0.15). In sex-stratified models, number of psychotherapy sessions, baseline severity, and shorter treatment duration remained associated with improvement in both sexes. In the sensitivity analysis (n = 63), baseline severity was the only significant predictor of treatment outcome. CONCLUSION:Higher baseline PTSD severity was the most robust predictor of symptom reduction. Session intensity and treatment timing may matter, but associations should be interpreted cautiously given the predominance of poor-quality studies and require replication in prospective trials with standardized protocols and longer follow-up.
INTRODUCTION:Around a third of patients with major depressive disorder experience persistent symptoms despite usual treatments. Identifying scalable psychological treatment options is critical to reduce the burden associated with difficult-to-treat depression (DTD). We examined the efficacy of mindfulness-based cognitive therapy (MBCT) compared with treatment as usual (TAU) and other active psychosocial controls in current DTD, and explored potential moderators. METHODS:We conducted an individual patient data (IPD) meta-analysis of randomised controlled trials comparing MBCT with TAU or other active psychosocial controls in currently depressed adults meeting criteria for treatment non-response, treatment resistance, or chronic course. Seven studies (N = 777) contributed data. Bayesian one-stage models were used as primary approach to estimate pooled effects on depressive symptom severity. RESULTS:MBCT was likely superior to TAU at post-treatment (standardised mean difference = -0.40; 95% credible interval [CrI] = -0.64 to -0.16) and medium-term follow-up (-0.41; 95% CrI = -0.76 to -0.02), with posterior probabilities of 92% and 85% of surpassing a clinical relevance threshold of d = -0.24, respectively. In contrast, comparative effects relative to other psychosocial interventions were uncertain, with no evidence of superiority. Moderator analyses did not identify robust predictors of outcome, suggesting broadly consistent effects across baseline severity, chronicity, and comorbidity. CONCLUSION:MBCT appears to be an effective and safe option for DTD, superior to TAU, with benefits maintained at medium-term follow-up, although no evidence of superiority over other active psychosocial interventions was observed. These findings support the integration of MBCT into comprehensive treatment models for DTD.
Introduction: Different disorder courses contribute to the large heterogeneity within depressive syndromes. Chronic depression (CD) warrants further investigation given its high prevalence and poor treatment outcomes. This study aimed to identify a clinical profile and symptomatic phenotype associated with CD versus non-chronic depression (NCD) to provide a better characterization of CD. Methods: The preregistered analysis used cross-sectional data from a large German cohort (N = 994; 64.9% female) with retrospective information on depression trajectories. We assessed associations of nine psychological and social characteristics with CD in logistic regression models. We further examined symptom networks across disorder courses using Bayesian network analysis of Beck Depression Inventory (BDI-I) item-level data. Results: In our sample 18.5% of patients with depression met criteria for CD (nCD = 184), whereas 81.5% showed a non-chronic course (nNCD = 810). The characteristics childhood maltreatment, age of onset, neuroticism, extraversion, social networks, social support, psychosocial functioning, and psychiatric comorbidities were associated with CD in single regressions. In a combined model (R2 = 0.25), greater exposure to childhood maltreatment, lower extraversion, and lower psychosocial functioning were associated with CD, defining a clinical profile distinguishing CD from NCD. Symptom networks based on BDI-I items were highly similar across trajectories, differing only by the connection between past failure and self-contempt, which was unique to the CD group. Conclusion: Psychosocial factors, but not symptom profiles, distinguished CD from NCD. Thus, characteristics beyond classical depression symptoms seem more informative for differentiating depression trajectories. If confirmed longitudinally, these findings may improve prediction of depression trajectories and inform early intervention.