Journal of Psychiatric Research

Abstract Background Ketamine has emerged as an effective rapid-acting treatment for treatment-resistant depression (TRD), producing significant antidepressant effects within hours of administration. Given ketamine's capacity to induce states of heightened neuroplasticity and psychological openness, psychotherapy may represent a meaningful complement to its pharmacological effects - facilitating emotional processing, cognitive restructuring, and the consolidation of therapeutic gains. However, the adjunctive potential of structured psychotherapeutic support in ketamine-based interventions remains largely unexplored. Methods This preliminary, non-randomized, open-label clinical trial evaluated the adjunctive effects of ketamine-assisted psychotherapy (KAP) in an outpatient setting. Forty-six patients with TRD received eight weekly sessions of subcutaneous esketamine (0.5-1.0 mg/kg) and were allocated into two groups: esketamine without psychotherapeutic support (n = 23) and esketamine combined with structured KAP encompassing preparation, dosing accompaniment, and post-session integration (n = 23). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory-II (BDI-II) at multiple timepoints during treatment and at follow-up assessments up to six months after protocol completion. Results Both groups showed significant reductions in depressive symptoms throughout treatment. The KAP group demonstrated greater clinical improvement by the end of treatment, with between-group differences on the MADRS emerging at sessions 7 and 8. MADRS response and remission rates were 52.2% and 34.8% in the KET group, and 78.3% and 78.3% in the KAP group, respectively. BDI-II scores indicated earlier subjective improvement in the KAP group, with between-group differences emerging as early as the second session and persisting across multiple timepoints. No significant between-group differences were observed during the six-month follow-up, with both groups maintaining symptom reductions comparable to end-of-treatment levels. Conclusions These findings suggest that structured psychotherapeutic support may be associated with early clinical response and remission rates in subcutaneous esketamine treatment for TRD, potentially through facilitation of emotional processing, psychological flexibility, and behavioural change. Further controlled studies are needed to clarify the specific contribution of psychotherapy, investigate the mechanisms underlying this interaction, and optimize integrated treatment approaches for TRD. The trial was registered at https://ensaiosclinicos.gov.br/rg/RBR-1072m6nv . Keywords: esketamine; treatment-resistant depression; ketamine-assisted psychotherapy; innovative therapies.

Structured AbstractO_ST_ABSBackgroundC_ST_ABSPost-Traumatic Stress Disorder (PTSD) is a mental health condition affecting people who experience traumatic events. Trauma-exposed occupational groups report higher rates of PTSD than the general population. Current treatments, and access, often take months and may cause distress when people are required to talk about the trauma. ObjectiveTo determine the proof of concept of FIRST, a brief, non-trauma focussed therapy, in two separate populations with employment-associated PTSD. MethodTwo independent, single-arm, experimental therapy pilot trials were conducted. Trial one recruited 20 military veterans who received FIRST therapy via trained third-sector therapists. Trial two recruited 16 health and social care workers with FIRST therapy delivered by healthcare provider therapists. All participants were adults with PTSD (confirmed via CAPS-5 in trial one, and symptom score of [≥]33 on the PCL5 in trial two). Primary outcomes were recruitment feasibility, retention, data quality and reduction in PTSD symptoms. Secondary outcomes were anxiety and depression symptoms, daily life functioning and perceived health status. Veterans were followed up at 12 weeks post-enrolment and healthcare workers at 8 weeks. ResultsThe veteran trial progression criteria to main trial were met. Seventy-nine people screened eligible, 43 attended a CAPS-5 assessment; 20 had confirmed PTSD and were enrolled. Seventeen completed therapy and 12-week outcome measures. Mean PCL-5 scores decreased from 48.7 (SD = 13.02, n=20) at baseline to 23.5 (SD = 15.30, n=17) at 12-weeks. The healthcare worker trial obtained informed consent from 16 participants, 10 commenced therapy and were included in analysis with eight completing therapy. Mean PCL-5 scores decreased from 42.60 (12.23, (n=10) at baseline to 22.00 (19.92, n=8) at 8-weeks. ConclusionsProof of concept of FIRST was established. PTSD symptom reductions exceeded the PCL-5 minimal clinically important difference. Undertaking a fully powered randomised controlled trial of FIRST therapy is feasible within both healthcare and third sectors. HighlightsO_LIPost-traumatic stress disorder (PTSD) is more common in military veterans and health workers than the general population C_LIO_LITherapy can be challenging to commence and complete when it requires a focus on the trauma incident C_LIO_LIFIRST offers a promising, brief, non-trauma focused therapy for the treatment of PTSD C_LI

Background: Internet-based cognitive behavioral therapy (iCBT) is efficacious for panic disorder (PD), yet the mechanisms of change remain underspecified. Anxiety sensitivity (AS) is theoretically central to PD maintenance, but its role as a mediator has not been formally tested in Spanish-speaking populations using minimal-contact formats. This study evaluates the efficacy of the "Free from Anxiety" iCBT program and examines AS as a mediator of clinical outcomes. Methods: In a randomized controlled trial, 95 adults meeting DSM-IV-TR criteria for PD were assigned to an 8-week iCBT program with optional email support (n = 49) or a waiting-list control (n = 46). Primary outcome was PD severity (PDSS); secondary outcomes included anxiety sensitivity (ASI-3), general anxiety (BAI), and depression (BDI-II). Mediation was assessed via Baron and Kenny's framework with bootstrapping (5,000 resamples) to estimate the indirect effect of ASI-3 change on PDSS reduction. Results: The treatment group showed significant improvements across all measures compared to controls (PDSS: d = 0.76, 95% CI [0.10, 1.42]; mean d = 1.30). Mediation analysis confirmed that ASI-3 change partially mediated the treatment effect on PDSS (indirect effect = 1.85, 95% CI [0.36, 3.70]), accounting for 27.4% of the total effect. The direct effect remained significant (b = 4.89, p < .001). Intent-to-treat (ITT) analyses supported robustness (d = 0.47 to 1.47). Gains were maintained at 6-month follow-up (d = 1.19 to 1.26). Conclusions: iCBT reduces anxiety sensitivity as a partial mechanism of change, aligning with cognitive models of panic. These findings support Free from Anxiety as an evidence-based, viable first-step intervention for Spanish-speaking clinical populations within stepped-care pathways.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with changes in motivation to work for rewards being a core symptom. Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising therapy but its effects on the core features of MDD, such as changes in motivation, remained relatively unexplored. In this randomised, single-blind, cross-over, controlled trial, we used a grip strength effort task to investigate how tVNS impacted choices to exert different levels of physical effort for varying monetary rewards in MDD patients (n=53) and a non-depressed control group (n=45). Compared to sham stimulation, tVNS enhanced the efficiency with which participants with severe depressive symptoms allocated physical effort for rewards (reward-effort efficiency). These effects were not seen in participants with less severe symptoms. Specifically, we found that the effect of tVNS on reward-effort efficiency was driven by reduced unnecessary effort, i.e., a reduction in choices to exert additional effort when this was not required to gain a larger reward. These findings suggest a potential motivational mechanism by which tVNS exerts its therapeutic effects in MDD. Determining whether the effects of tVNS are linked to broader changes in executive functioning, such as improvements in cognitive flexibility in MDD, should be a key aim for future work.

Background: Childhood adversity (CA) is recognized as a distal risk-factor for suicide attempts (SA) in individuals with psychiatric disorders. However, not all individuals with experiences of CA will engage in SA. Contributing to this relationship may be proximal factors such as impulsivity, inward anger and self-aggression. However, these factors are often conceptually blended and measured in different samples. We sought to clarify association among CA and personality factors in persons with SA. Methods: Participants from two studies comprised individuals with a diagnosed psychiatric disorder and history of SA (n= 139) and individuals with depressive disorder (clinical controls, CC; n= 24). We investigated self-reported levels of CA, impulsivity, inward anger, and self-aggression between the SA and CC (pcorr< .012). We tested the relationship among the factors using regression (pcorr<.017) and mediation model (indirect effects, p<.05) within the SA group. Sensitivity models were run controlling for age, gender, symptom severity, trait anger, and externally oriented aggression. Results: SA group had higher impulsivity (pcorr=.067) in a model controlled for age and gender. Other factors did not differ among groups. Within the SA group the analyses revealed positive association among CA and personality factors (pcorr<.06) in basic and model with age and gender, however the association was not specific for internally (self) oriented factors (coefficient comparison, p<.07). Parallel mediation model indicated that CA had indirect effect on self-aggression through impulsivity (p=.001) and to a lesser extent through inward anger (p=.066). Generally, models controlling for cognitive depression symptoms showed less prominent effects (pcorr>.1). Limitations: The study was cross-sectional and did not include behavioral tasks (state) measures of proximal factors. Conclusions: CA and personality factors showed similar severity levels among the SA and CC groups suggesting they may relate to broader psychopathologies, rather than specifically to SA. The association of CA with anger and aggression was unspecific to internally oriented factors indicating the need for more precise measuring instruments developed specifically for individuals with SA. Overall, the study highlights personality factors as being associated with risk in broader vulnerable populations.

Background: Generalized anxiety disorder (GAD) is associated with substantial psychological burden, autonomic dysregulation, and limitations of existing pharmacological and psychotherapeutic treatments. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising non-invasive neuromodulation approach, but evidence regarding home-based application in GAD remains limited. Objective: To evaluate the feasibility, safety, and preliminary clinical and physiological outcomes of a home-based taVNS intervention in adults with psychologist-confirmed moderate-to-severe GAD. Methods: In this prospective single-arm feasibility study, 48 participants initiated a 4-week home-based taVNS intervention consisting of two daily stimulation sessions performed five days per week. Clinical assessments were conducted at baseline, Week 2, Week 4, and follow-up visits at Weeks 6 and 8. Ambulatory electrocardiographic monitoring was performed before treatment initiation, at Week 2, and at the end of treatment to assess heart rate variability (HRV) using the root mean square of successive differences (RMSSD). Primary outcomes included feasibility, safety, adherence, and change in clinician-rated anxiety severity (HAM-A). Results: Thirty-four participants completed the study and were included in the primary analyses. HAM-A scores decreased significantly from baseline to Week 4 ([EMD] -6.9, 95% CI -10.4 to -3.4, p = 0.001), with partial maintenance during follow-up. Improvements were also observed in Beck Anxiety Inventory scores, whereas changes in GAD-7, perceived stress, depressive symptoms, and sleep quality were not statistically significant. RMSSD increased significantly from baseline to Week 4 (EMD 6.7 ms, 95% CI 2.1-11.3, p = 0.009). Greater increases in RMSSD were associated with larger reductions in HAM-A (R^2 = 0.18, p = 0.031) and BAI scores (R^2 = 0.21, p = 0.019). No serious adverse events occurred. Mean adherence was 79.8%, and 73.5% of participants completed at least 70% of prescribed stimulation sessions. Conclusions: Home-based taVNS was feasible and generally well tolerated in adults with moderate-to-severe GAD. Preliminary improvements in clinician-rated anxiety severity and autonomic physiological measures were observed; however, the single-arm design precludes causal inference. These findings support further evaluation of home-based taVNS in adequately powered randomized sham-controlled trials.

BackgroundIntermittent theta burst stimulation (iTBS) and H-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. MethodsTwenty-eight adults with TRD were randomized to six weeks of iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) using a figure-8 coil (n=15) or H-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) using a H7-coil (n=13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. ResultsTwenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for iTBS and 50.0% for H-coil (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. ConclusionIn this pilot trial, iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group pattern. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. Trial registrationClinicalTrials.gov (NCT05902312)

Esketamine is a fast-acting antidepressant drug which induces acute psychoactive effects. The most frequent is a dissociative state which seems unrelated to therapeutic efficacy. Other esketamine-induced effects, including psychedelic-like mystical experiences, have been poorly studied in terms of phenomenology and frequency, and may carry specific therapeutic relevance. In this study, we characterised esketamine-induced mystical experiences in relation with clinical outcomes. We conducted a longitudinal observational study and systematically measured acute subjective effects in patients receiving esketamine for treatment-resistant depression after each administration across the induction phase. A total of 45 patients were included, from two independent centres, totalling 352 esketamine administrations. Principal Component Analysis (PCA) supported the validity of the Mystical Experience Questionnaire (MEQ-30) for assessing esketamine-induced subjective effects, with components recovering dimensions previously validated with classic psychedelics. Mystical experiences (MEQ-30 score above 60) occurred in 58% of patients, with high inter- and intra-individual variability in frequency, intensity, and phenomenology across sessions. Higher mean and peak MEQ scores were associated with greater improvement in Montgomery-Asberg Depression Rating Scale scores from pre- to post-treatment, whereas the intensity of dissociative or other non-mystical effects was not. Positive mood and mystical MEQ dimensions in particular predicted therapeutic outcomes. Baseline spirituality also significantly predicted treatment outcomes and peak MEQ scores in the first week of treatment. These findings add to the growing body of evidence suggesting that psychedelic-like mystical experiences may be associated to therapeutic efficacy, not only in classic psychedelic-assisted therapy, but also in esketamine treatment.

Introduction Experiential acceptance refers to the capacity to be open to internal experiences without attempting to change or avoid them. Although acceptance is a core emotion regulation strategy within mindfulness- and acceptance-based interventions (MABIs) and a protective factor for mental health, its conceptualization and implementation remain unclear and ambiguous. The aim of this study was to clarify and develop a comprehensive model of accepting anxiety. Method Twenty-six participants from a non-clinical sample with prior experience in MABIs took part in semi-structured interviews exploring their experience of accepting anxiety. Data collection and analysis followed the principles of Grounded Theory to generate a data-driven model of the acceptance process. Results We identified a five-stage dynamic model involving distinct processes: (Stage 1) observing through the body with attentional focus on interoceptive experience; (Stage 2) identifying and acknowledging anxiety; (Stage 3) validating and normalizing the experience through validation and self-compassion; (Stage 4) not reacting characterized by decentering and nonreactivity; and (Stage 5) staying with the experience via exposure. We also identified facilitating factors that support engagement in the acceptance process. Conclusion These findings refine the understanding of acceptance as a multidimensional emotion regulation process by highlighting an active dynamic involving multiple mechanisms underlying the acceptance of anxiety. This model provides a framework for developing more targeted clinical interventions and for investigating individual and contextual variability in these subprocesses.

Separate research has evaluated trajectories of posttraumatic stress symptoms (PTSS) and obsessive-compulsive symptoms (OCS), but no study has evaluated OCS trajectories following trauma exposure nor combined PTSS/OCS trajectories. The present study evaluated combined PTSS/OCS trajectories among 585 survivors of Hurricane Helene, spanning three waves of data collection over 12 months. A 3-class solution was supported, including resilient (i.e., consistently low PTSS and OCS), chronic (i.e., elevated PTSS and OCS with gradual reduction over time), and moderate-yet-diverging (i.e., moderate elevations in PTSS and OCS with gradually declining PTSS and persistent and increasing OCS over time) classes. This study shows both overlap and differentiation in symptom trajectories from earlier research, with the moderate-yet-diverging trajectory suggesting unique OCS pathways distinct from PTSS.

Background: Hydrogen sulfide (H2S) is an endogenous gasotransmitter synthesised in the central nervous system (CNS) primarily by cystathionine {beta}-synthase (CBS) and cystathionine {gamma}-lyase (CSE). Pre-clinical studies consistently implicates H2S deficiency in the pathophysiology of depression through disruption of synaptic plasticity, neuroinflammation, oxidative stress, and brain-derived neurotrophic factor (BDNF) signalling. Yet, we still lack direct clinical evidence quantifying circulating H2S in patients with Major Depressive Disorder (MDD), particularly from South Asian populations. In this study, we measured serum H2S levels in drug-naive patients with MDD and compared them with healthy controls at a tertiary care center in eastern India. We examined the associations between serum H2S and depression severity as assessed by the 17-item Hamilton Depression Rating Scale (HAM-D-17). This institution-based, cross-sectional analytical study was conducted at North Bengal Medical College and Hospital (NBMCH), West Bengal, India, over 12 months. Fifty drug-naive patients fulfilling DSM-5 criteria for MDD and fifty age- and sex-matched healthy controls were enrolled by consecutive sampling. We quantified serum H2S using the spectrophotometric methylene blue method and depression severity was assessed using HAM-D-17. Statistical analyses included independent-samples t-test, chi-square test, and linear regression. Serum H2S was markedly and significantly lower in MDD patients (0.068 {+/-} 0.044 {micro}mol/L) compared with healthy controls (0.524 {+/-} 0.272 {micro}mol/L; p < 0.001), representing an approximately 7.7-fold reduction. HAM-D-17 scores were significantly higher in MDD patients (28.94 {+/-} 12.78) than in controls (3.96 {+/-} 2.31; p < 0.001). Linear regression across the combined cohort revealed a significant negative association between serum H2S and HAM-D score (R{superscript 2} = 0.287; y = 24.64 - 26.84x; p < 0.001), indicating that higher serum H2S was associated with lower depression severity. Within the MDD group alone, the regression was weak (R{superscript 2} = 0.061), consistent with a floor effect. Within the control group alone, the regression was strong (R{superscript 2} = 0.772). No significant associations were found between serum H2S and any sociodemographic variable in either group. Drug-naive MDD patients exhibited substantially reduced serum H2S levels compared with healthy controls, and lower H2S was associated with greater depression severity. These findings provide direct clinical evidence from an Indian population supporting the H2S deficiency hypothesis of depression and suggest that the CBS/CSE-H2S axis may represent a novel biomarker and therapeutic target in MDD. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/26352330v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1ce64f6org.highwire.dtl.DTLVardef@1465ca2org.highwire.dtl.DTLVardef@6bba64org.highwire.dtl.DTLVardef@9a1411_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background Treatment guidelines for borderline personality disorder (BPD) recommend assessment, diagnosis, and psychoeducation. We report on the feasibility and safety of a randomized controlled trial protocol of online psychoeducation, assessment, and personalized feedback as an immediate first step of care for BPD. Methods Newly diagnosed participants were randomized to receive 10 videos about BPD or general mental health for two weeks. Half the participants receiving BPD videos were randomized to receive personalized feedback on changes in symptom ratings and cognitive performance. Ecological momentary assessment (EMA) evaluated interpersonal interactions, emotions, and behaviors for 30 days. BPD symptoms, depression, and personality functioning were assessed at baseline, after videos, after feedback, and one month later. Results Eighty-two participants were randomized into three conditions that did not differ significantly in terms of demographics or baseline variables. Dropout occurred for 32.9% of the sample. No differences in rate of emergency room visits, hospitalizations, or other escalations in level of care were reported among groups. Satisfaction was higher for those receiving psychoeducational videos about BPD. Improvement in BPD knowledge in the psychoeducation conditions was significantly greater than the control condition. No statistically significant differences were found regarding reduction of BPD symptoms. The psychoeducation with feedback arm showed significantly greater improvements in self-impairment compared to controls with medium effect size at the final timepoint. Modeling of the relationship between time spent alone and BPD symptoms showed a positive correlation in the control condition, but in the group receiving both psychoeducation about BPD and feedback, this relationship was negative. Conclusion Online psychoeducational videos and assessment were safe, feasible, and acceptable to participants with newly diagnosed BPD. Psychoeducation with personalized feedback appears to be more effective than either BPD or general psychoeducation alone in improving deficits in self-functioning, which may relate to an increased capacity to be alone with fewer symptoms. The protocol was registered with ClinicalTrials.gov (NCT05358925, https://clinicaltrials.gov/study/NCT05358925) on April 28th, 2022.

Background. Adolescence and young adulthood represent critical developmental stages during which mental disorders often emerge, with the potential to impede perceived quality of life. Spirituality (i.e., the search for the sacred) and self-regulation (i.e., intrinsic processes regulating emotions, thoughts, and behaviors) are recognized as protective factors for mental health. However, their dynamic interplay remains largely unexplored, particularly in real-life and in real-time among youths. This study, developed with the help of young partners, addresses this gap by investigating the longitudinal associations between spirituality, self-regulation, and mental health using an ecological momentary assessment (EMA) approach. Methods and analysis. We plan to recruit 120 adolescents and young adults (aged 16 to 20, expected attrition rate of 20%) from the community to complete a qualitative semi-structured interview assessing their beliefs, spiritual or religious activities, role models, and meaning in life. In addition, participants will take part in a multi-wave intensive longitudinal study. Trait-level assessments will be conducted at two time points, three months apart, to capture between-person differences. Additionally, to assess within-person dynamics, participants will complete EMA surveys four times daily over 10 consecutive days in two waves, also three months apart. Measures will include facets of spirituality (e.g., beliefs, meaning, collective consciousness), self-regulation (e.g., self-control, emotional regulation, impulsivity), as well as mental health indicators (emotional and behavioral symptoms) and quality of life. Qualitative data will be analyzed through a thematic analysis method, whereas quantitative associations will be assessed using Linear Mixed Models (LMM) and network analyses. Ethics and dissemination. Ethical approval has been obtained, and data collection begun in May 2025. Findings will be disseminated through open access peer-reviewed journals, conferences on adolescent mental health, and shared with practitioners, educators, and youth organizations. Results will also be made accessible to the general public. This study aims to inform personalized preventive and therapeutic interventions by elucidating real-time mechanisms linking spirituality, self-regulation, and mental health in youths.

Background: Dissociative experiences encompass a variety of discontinuities in awareness and perception that are elevated in the dissociative disorders and associated with extensive comorbid symptomatology. Accumulating evidence points to developmental trauma and trait responsiveness to verbal suggestions (REVS) as factors that confer risk for severe dissociative symptoms, but they have typically been studied in isolation. This study integrated these measures using prediction modelling to better understand their predictive value for the risk of dissociative psychopathology. Method: 1,104 non-clinical participants completed measures of trauma, dissociation and trait REVS. The predictive model was developed using elastic net logistic regression, internally validated with 10-fold cross-validation, and assessed using receiver operating characteristic (ROC) curve and area under the ROC (AUROC). Variables entered into the model were components of REVS, trauma, age, and their interactions. Results: A dissociative psychopathology at-risk group (7%) was characterised by younger age, greater trauma and elevated REVS, particularly involuntariness during cognitive-perceptual suggestions. The prediction model retained nine of ten predictors, with an AUROC of .77 [95% CI: .73, .82], reflecting good discrimination with moderate sensitivity (78%) but modest specificity (67%). Conclusions: These findings reinforce trauma and trait REVS as risk factors for dissociative psychopathology and demonstrate that they can be integrated in a model that can identify at-risk individuals. Further validation and extension of the model is necessary to improve the identification of individuals at risk for severe dissociative symptomatology and the diagnosis of dissociative disorders with implications for outcome trajectories.

Hoarding disorder (HD) affects approximately 2-3% of adults and is associated with substantial functional disability and limited access to evidence-based care. The aim of the current analysis was to examine the naturalistic effectiveness of therapist-delivered video cognitive-behavioral therapy (CBT) for HD in a large real-world sample, and to characterize individual-level treatment response, time-to-response, and moderators of outcome. This retrospective, observational analysis examined clinical data from 305 adults diagnosed with HD who received therapist-delivered video CBT through an online specialty therapy platform between September 2021 and February 2026. Hoarding symptom severity was assessed using the Hoarding Rating Scale-Self Report (HRS-SR). Linear mixed models examined symptom change from baseline to three timepoints: session 10, session 20, and each patient's final session. HRS-SR scores decreased from M = 22.4 (SD = 7.6) at baseline to M = 16.4 (SD = 8.2) at final session (Hedges' g = 0.81, 95% CI: 0.68-0.94). By the final session, median percent improvement was 25.0% [IQR: 3.0-46.7%]. A total of 39.3% of patients achieved [&ge;]35% HRS-SR reduction, 27.4% of patients who began above the clinical threshold achieved remission, 36.4% demonstrated reliable improvement, and 22.9% of eligible patients achieved clinically significant change. Among patients who achieved and maintained [&ge;]35% reduction through their final session (n = 120), median time to first response was session 9, with 54.2% responding within 10 sessions. Analyses of secondary outcomes showed significant improvements in clutter severity, depressive and anxiety symptoms, stress, quality of life, and functional disability (Hedges' g = 0.21-0.47). Greater baseline severity, more sessions, and longer treatment duration significantly moderated outcomes; prior OCD treatment history did not. Findings suggest that therapist-delivered video CBT for HD, delivered remotely in a real-world setting, produces outcomes consistent with controlled trials and may be a clinically effective and scalable approach for a condition historically underserved by mental health systems.

BackgroundTranscranial alternating current stimulation (tACS) is a promising non-pharmacological intervention for major depressive disorder (MDD), but its effects on endogenous alpha oscillatory dynamics and their relationship to clinical improvement remain unclear. MethodsIn this double-blind, sham-controlled randomized clinical trial, 20 adults with MDD received five consecutive days of prefrontal 10 Hz tACS or sham. Resting 128-channel EEG was acquired before stimulation on Day 1 (D1), Day 5 (D5), and two-week follow-up. Changes in alpha power spectral density were quantified at the stimulation frequency (10 Hz) and at each participants individual alpha frequency (IAF), using prefrontal regions of interest and whole-head topographical analyses. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-17). ResultsBetween-group comparisons revealed no significant differences in prefrontal alpha power changes at either 10 Hz or IAF during the intervention week or at follow-up, although right prefrontal 10 Hz power showed a trend-level reduction with tACS. In contrast, within the tACS group, greater reductions in prefrontal IAF power were associated with greater HDRS-17 improvement from D1 to follow-up, and early IAF power suppression during the intervention week predicted later symptom improvement. Whole-head analyses identified a posterior cluster of reduced 10 Hz power at follow-up in the tACS group relative to sham, whereas clinically relevant correlations were specific to IAF power and distributed across frontal-central and parietal electrodes. Depression scores improved over time in both groups, with greater reductions in HDRS-17 scores observed in the tACS group. ConclusionsFindings suggest that five days of 10 Hz tACS engages depression-relevant alpha mechanisms, with symptom improvement linked specifically to modulation of alpha power at IAF. Results support personalization of tACS in future trials.

Background: While growing enthusiasm for the therapeutic potential of classic psychedelics has led to a rise in non-clinical use, attention to persisting adverse effects has emerged with delay. A subset of individuals reports persisting complications such as hallucinogen persisting perception disorder (HPPD), depersonalization/derealization disorder (DDD), anxiety and depression. Yet few medical services are equipped to address these complications. Aims: This qualitative study examines how societal, medical, and media discourses shape the experiences of individuals with persisting psychedelic-related complications, focusing on help-seeking trajectories. Methods: Thirteen semi-structured interviews with adults experiencing persisting psychedelic-related psychological symptoms (four women, nine men, age 19-49 years; HPPD (n = 10), DDD (n = 6), depression (n = 1), and anxiety (n = 1)) were conducted within a larger study on these complications. Data were analysed using reflexive thematic analysis. Reporting followed the COREQ guidelines. Results: Three interrelated themes emerged: (1) The dissonance between expectation and harm - idealised media and scientific portrayals of psychedelics shaped initial use and complicated recognition of adverse outcomes; (2) Stigma, silence, and self-blame - prohibitionist discourse and internalised shame significantly inhibited help-seeking; and (3) Between systemic absence and self-organised support - participants encountered clinical unpreparedness and epistemic dismissal, which often led them to rely on online peer communities and self-management strategies. Positive clinical encounters, characterised by professional expertise and nonjudgmental engagement, were experienced as helpful. Conclusions: Adequate clinical and conceptual frameworks for persisting psychedelic-related complications are lacking. An interdisciplinary, experience-informed approach integrating realistic risk communication, clinician training, and destigmatisation is required to support affected individuals.

Background Somatic and psychological symptoms like depression, anxiety, and trauma-related stress often co-occur, especially in young adults, a group facing major life transitions and increased vulnerability. These overlapping symptoms pose diagnostic challenges that traditional disorder-specific models capture poorly. Transdiagnostic and dimensional approaches may offer a more meaningful framework. However, population-based data on symptom patterns in young adults remains sparse. This study investigated the patterns of psychological and somatic symptoms among young adults from Switzerland and compares these results to findings from populations with different stress exposure histories: Ukrainians who fled to Switzerland, and Ukrainians living in different regions in Ukraine during the war. Methods We analyzed cross-sectional baseline data collected in spring 2024 as part of the Mental Health Assessment of the Population (MAP) studies, where we enrolled randomly selected young adults aged 18-24 from Switzerland, Ukrainian refugees in Switzerland, and Ukrainians residing in regions with different degrees of proximity to active war zones. We assessed somatic (PHQ-15) and psychological symptoms (PHQ-9, GAD-7, PCL-5) and explored symptom patterns using descriptive statistics, correlations, and k-means clustering. Results Psychological symptom severity showed highly consistent moderate-to-strong correlations with somatic symptoms (range: 0.53-0.69), across all young adult subgroups and disorders. Rather than identifying disorder-specific patterns, symptoms clustered by overall symptom severity, emerging in three clusters: (1) high symptom burden, (2) moderate symptom burden, and (3) low symptom burden clusters with elevated somatic, depressive, anxiety, and PTSD symptoms. The cluster structure was remarkably stable across Swiss, Ukrainian, and refugee subsamples, despite markedly different stress exposure histories. Conclusion Our results support a symptom-based, dimensional approach to understanding mental health in young adults and to better capture the complexity and co-occurrence of psychological and somatic symptoms in this age group. These findings further suggest that prevention and early detection strategies should more systematically integrate both psychological and somatic symptomatology.

ObjectiveCognitive behavioral therapy (CBT) is an effective first-line treatment for obsessive-compulsive disorder (OCD), yet it remains difficult to predict who will respond to this intervention. This study investigates associations between neural activity during inhibitory control tasks and CBT outcomes, and whether task-based fMRI data could serve as a predictive marker of individual CBT response. MethodsUsing fMRI data from individuals performing an inhibitory control task across five samples (n=130, age range=8-57, 54% female) of the ENIGMA-OCD consortium, univariate associations were analyzed between activity during response inhibition and error processing and three CBT outcomes: response, remission, and pre-post treatment change in symptom severity. Random forest and support vector machine models using leave-one-sample-out cross-validation were used for prediction of CBT response and remission from fMRI activity and clinical data. ResultsRemission after CBT was associated with weaker activity in default mode regions during response inhibition and in the right supramarginal gyrus during error processing. Greater symptom reduction was linked to weaker pre-treatment activity across frontoparietal, dorsal attention, visual, and subcortical regions during response inhibition, but to stronger default mode activity during error processing. Despite these robust group-level effects, machine learning models failed to predict individual outcomes above chance level with either neuroimaging or clinical data. ConclusionWeaker activity during response inhibition in a widespread network, as well as stronger activity in default mode regions during error processing before treatment, appear beneficial to CBT response. However, these findings cannot yet be translated into individually predictive markers of CBT outcome.

Objective: Biopsychosocial models recognize multiple determinants of post-trauma mental disorders, but their relative and interactive effects remain unclear. We quantified the independent contribution of traumatic event severity, preexisting vulnerability, social support, and coping capacity, and tested mediation pathways. Methods: In a Brazilian clinical sample reporting traumatic or stressful events (N = 612), constructs were operationalized as composite scores and a dichotomous clinical outcome was derived from intake assessments. Logistic regression (n = 594) and structural equation modeling evaluated prediction and mediation. Results: Vulnerability was the strongest risk factor (OR = 1.46, p < .001) and social support the main protective factor (OR = 0.60, p < .001). Traumatic event severity remained an independent predictor (OR = 1.39, p < .001), whereas coping capacity was not significant (OR = 0.94, p = .410). Discrimination was good (AUC = 0.80). Mediation indicated vulnerability reduced social support and coping capacity, with a significant indirect effect via social support. Conclusions: Findings support a multifactorial model centered on a triad of vulnerability, social support, and traumatic exposure. Risk is shaped primarily by preexisting vulnerability and relational context, alongside a direct trauma effect, providing a clinically relevant framework for assessment and intervention.