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PubMed2026

Investigating telomere length and hTERT-MNS16A VNTR polymorphism in Bipolar disorder: Insights into clinical features.

OBJECTIVE: To compare leukocyte telomere length (LTL; T/S ratio) and hTERT-MNS16A VNTR polymorphism between patients with bipolar disorder (BD) and healthy controls, and to examine their associations with clinical features in BD. METHODS: A total of 179 participants (100 BD patients, 79 healthy controls) were enrolled. Relative LTL was assessed by qPCR-based T/S ratio; hTERT-MNS16A VNTR genotyping by PCR and gel electrophoresis. Clinical variables including episode frequency, illness duration, age at onset, symptom severity scales, first episode polarity, and family history of mood disorder were evaluated. RESULTS: No significant differences were observed between BD patients and healthy controls in T/S ratio or hTERT-MNS16A VNTR genotype distributions (all p > 0.05). Within the BD group, S allele carriers (L/S or S/S) had significantly more depressive episodes than L/L homozygotes (1.45 ± 2.58 vs. 0.61 ± 1.52; p = .040). Significant inverse correlations were identified between T/S ratio and depressive episode count (ρ = -0.220, p = .028) and total mood episodes (ρ = -0.207, p = .039). Multivariable negative binomial regression revealed four independent predictors of depressive episode frequency: lower T/S ratio (p = 0.005), S allele carriage (L/S or S/S genotypes) (p = 0.001), first depressive episode polarity (p < 0.001), and family history of mood disorder (p = 0.035). CONCLUSION: Although LTL and hTERT-MNS16A VNTR genotype did not differ between BD patients and healthy controls, shorter telomere length and S allele carriage were independently associated with higher depressive episode frequency within the BD group, implicating telomere biology and hTERT genetic variation in the biological substrate of depressive illness burden.

Humans↗

PubMed2026

Immune dysregulation in depression and psychosis: summary of current evidence and future perspectives.

Despite compelling epidemiological, genetic and cellular evidence linking immune dysregulation to depression and schizophrenia (and other psychotic disorders), causality remains contested and no immune biomarker has yet demonstrated robust clinical utility. Emerging methodological approaches - from target trial emulation on observational data to functional genomics - offer a potential path towards precision immunopsychiatry and stratified immunomodulatory treatment.

Neuroimmunology↗

PubMed2026

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I. = 50-66%) and Alzheimer's dementias(28.0% = 95%C.I. = 17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I. = 17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I. = 36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I. = 38.3-45.6%), anxiety(32.0%;95%C.I. = 26.5-37.6%), MDD + anxiety(24.7%;95%C.I. = 17.9-34.3%), and dementia(19.8%;95%C.I. = 12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I. = 21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I. = 12.0-46.0%), MDD in PVI patients (20.0%;95%C.I. = 13.0-29.0%); in coronary artery disease: MDD + anxiety(19.8%;95%C.I. = 16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I. = 0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I. = 0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I. = 0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans↗

PubMed2026

Applications of quantum AI in brain disorder diagnosis: A systematic review.

BACKGROUND AND OBJECTIVE: Brain disorder diagnosis and prediction remain challenging because neuroimaging, electrophysiological, behavioral, and multimodal data are high-dimensional, noisy, heterogeneous, and limited by small clinical cohorts. This systematic review synthesised applications of quantum artificial intelligence (QAI) for brain disorder diagnosis, prediction, detection, and monitoring. METHODS: Following PRISMA guidelines, studies published from 2016 to 13 January 2026 were retrieved from Scopus, Web of Science, and IEEE Xplore. After screening, 36 studies met the eligibility criteria and were qualitatively analysed according to disorder category, data modality, QAI method, implementation setting, validation strategy, and performance. RESULTS: At the broader disease-group level, neurodegenerative disorders were the most frequently investigated, followed by mental health and psychiatric disorders. At the individual level, Parkinson's disease and schizophrenia were the leading applications, followed by depression, anxiety, Alzheimer's disease, and stress-related tasks. MRI-based modalities were the most frequently used data source, followed by multimodal data and EEG. Methodologically, primary QAI approaches were dominated by quantum neural and QDL architectures, followed by quantum-inspired optimization or feature-selection methods and quantum-kernel/conventional QML classifiers. Qiskit/IBM Quantum and PennyLane were the most frequently reported quantum software frameworks. However, most studies relied on simulators, classical quantum-inspired implementations, or unclear implementation settings, with limited real-hardware evaluation. CONCLUSIONS: QAI shows emerging potential for brain disorder analysis, particularly through hybrid quantum-classical learning, quantum neural architectures, quantum-kernel methods, and quantum-inspired optimization. Nevertheless, current evidence remains preliminary and requires larger datasets, subject-level and external validation, fair classical benchmarking, noise-resilient circuits, real quantum hardware evaluation, explainability, and clinical validation.

Humans↗

PubMed2025

Systematic Review of Symptoms of Catatonia in Autism Spectrum Disorder.

Catatonia is a complex neuropsychiatric syndrome characterized by disturbances in mood, motor function, behavior and speech. It is increasingly recognized in individuals with autism spectrum disorder (ASD), although its identification remains challenging due to the overlapping clinical features of the two conditions. Shared characteristics, such as echophenomena, mannerisms, social indifference and repetitive behaviors can obscure accurate diagnosis. Although reports suggest a significant prevalence of catatonia among individuals with ASD, the condition remains poorly understood and frequently under recognized, leading to substantial diagnostic and treatment challenges. A systematic review was conducted to characterize the symptoms of catatonia in individuals with ASD. The literature search included peer-reviewed journal articles published in English from 1980 onward, focusing on studies examining co-occurring catatonia and ASD. A qualitative framework analysis was implemented to evaluate 45 peer-reviewed studies, with findings interpreted in relation to, and extending beyond, the diagnostic criteria for catatonia outlined in the International Classification of Diseases, 11th revision (ICD-11). The objective was to identify symptom patterns extending beyond current diagnostic frameworks and to support improved clinical recognition and diagnostic precision in ASD populations. The review identified six primary symptom clusters associated with catatonia in individuals with ASD: (1) psychomotor activity, (2) speech disturbances, (3) changes in behavior/skills/functions, (4) mental health symptoms, (5) physiological symptoms, and (6) symptoms related to arousal and awareness. Notably, several symptoms observed within these clusters are not currently included in the ICD-11 diagnostic criteria for catatonia. These additional symptoms include tics, motor compliance, incoherent speech, self-injury, impaired cognition, and appetite changes, suggesting a broader clinical presentation of catatonia in ASD populations than is presently captured in existing diagnostic frameworks. The findings of this review highlight the significance of enhancing clinicians' awareness and understanding of how catatonia manifests in individuals with ASD. Most notably, six symptom clusters, psychomotor changes, speech disturbances, behavioral and functional regression, affective and psychiatric symptoms, physiological symptoms, and arousal/awareness disturbances, were observed. Several symptoms identified in this review are not included in the current diagnostic criteria, and their recognition may facilitate in earlier identification and timely intervention, potentially preventing the severe consequences of untreated catatonia in this population.

Humans↗

PubMed2026

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4⁺ regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogotá, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (∼2.4-fold decrease in median expression; p = 0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p = 0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p = 0.035) and Amerindian ancestry (p = 0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent↗

PubMed2026

Effectiveness of peer recovery support services for substance use disorders: A systematic review of healthcare utilization, behavioral health, and engagement outcomes.

BACKGROUND: Peer recovery support services (PRS) delivered by individuals with lived experience of substance use, are increasingly incorporated into substance use disorder (SUD) care systems to improve care engagement, reduce acute care use, and support recovery. However, existing systematic reviews have focused on substance use outcomes, with limited attention to healthcare utilization, psychosocial functioning, and outcomes across settings, and populations. METHODS: This systematic review, registered in PROSPERO (CRD42023469279), synthesized peer-reviewed studies from 2003 to 2026 evaluating PRS for individuals with alcohol or drug-related SUD. Using MEDLINE, Embase, PsycINFO, and CINAHL, the review included 53 studies primarily conducted in high-income countries that reported quantitative outcomes across substance use, healthcare utilization, behavioral health, and treatment engagement. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and ROBINS-E tools. RESULTS: Overall, evidence was most favorable for selected treatment-linkage and engagement outcomes, whereas findings for substance use, emergency department use, hospitalization, overdose, and mortality were inconsistent. Uncontrolled longitudinal studies frequently reported improvements in depression and anxiety, but no randomized trials evaluated these outcomes, limiting causal inference. Exploratory cross-study patterns suggested that sustained navigation, practical assistance, and repeated peer contact were more often present in programs reporting favorable outcomes; however, these components were not independently evaluated. Substantial heterogeneity, frequent multicomponent interventions, high risk of bias in many nonrandomized studies, and limited long-term and economic data constrain conclusions. CONCLUSIONS: Findings support the promise of PRS while underscoring the need for more rigorous comparative studies, cost-effectiveness data, and further research in low- and middle-income countries.

Humans↗

PubMed2026

Repetitive transcranial magnetic stimulation in substance use disorders is safe and tolerable: A Systematic review of 141 clinical trials including 4299 participants.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation intervention investigated as a treatment for substance use disorder (SUD) and its co-occurring disorders. As the number of rTMS SUD clinical trials increase, the safety and tolerability profile should be assessed. In this systematic review, we investigate adverse events (AEs) of rTMS in individuals with SUD and factors that may influence their occurrence. METHODS: We performed a systematic PubMed search to identify all controlled trials of rTMS in SUD published up to January 2025. Eligible studies were assessed, and safety information was extracted for analysis. RESULTS: A total of 141 clinical trials with 4299 participants were included in their active arms. rTMS trials recruited participants who were engaged in active substance use, were in the pre-treatment phase, in early recovery, or in sustained recovery. Twenty-two studies explicitly reported no AEs. Sixty-nine studies reported only mild AEs, while only six studies reported moderate AEs. Thirty-five studies did not report safety-outcomes/AEs. As expected, participants reported mild and temporary AEs such as headaches, pain or discomfort under the coil, or dizziness. Only nine studies reported serious AEs (7 studies in active TMS and 2 in sham TMS). Importantly, no seizures attributable to active rTMS were reported in these SUD samples. CONCLUSION: Overall, rTMS in SUD samples is safe and well-tolerated regardless of recovery stage and substance. Most reported side effects were mild, self-limiting, and tolerable. However, AE reporting was incomplete, as 35 of 141 trials reported no safety data, limiting conclusions to reported outcomes. This evidence supports the safety of rTMS as a potential stand-alone or adjunctive treatment for SUD.

Humans↗

PubMed2026

Implementing Prolonged Exposure Therapy in a Community Substance Use Treatment Program: A Qualitative Study.

INTRODUCTION: Post-traumatic stress disorder (PTSD) commonly co-occurs with substance use disorders (SUD), yet few community-based SUD programs incorporate evidence-based trauma-focused. Prolonged exposure (PE), including its massed format (M-PE) with session frequency of 3-4 times per week, is a gold standard intervention for PTSD; however, concerns about client readiness, logistical demands and relapse risk have limited its adoption within SUD settings. This study examined staff perspectives on the feasibility and acceptability of integrating M-PE into a community-based SUD program. METHODS: Prior to launching a Hybrid Type 1 effectiveness-implementation trial (Project COMET), we conducted semi-structured virtual interviews with 15 community clinic staff: providers (n = 8), administrators (n = 2) and peer specialists (n = 5). Interviews were recorded, transcribed and analysed using a rapid qualitative analysis framework with matrix techniques to compare themes across roles. RESULTS: Four overarching themes captured staff perspectives on integrating M-PE: (Theme 1) Prior Knowledge and Experiences: Most staff were familiar with EMDR, while direct knowledge of PE/M-PE was limited. (Theme 2) Perceptions of M-PE: M-PE was widely viewed as a promising, structured intervention that fits the pacing and duration of SUD care. (Theme 3) Symptom Reduction and Client Impact: Staff anticipated improvements in PTSD and SUD symptoms through trauma-focused treatment. (Theme 4) Barriers and Constraints: Participants identified several potential implementation challenges, including logistical barriers and client readiness. DISCUSSION AND CONCLUSIONS: Findings suggest that staff generally viewed M-PE favourably but emphasised the importance of ensuring client readiness and organisational support. Enhancing feasibility and long-term sustainability may require expanded psychoeducation, targeted provider training and flexible delivery models. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06968832.

Adult↗

PubMed2026

Linking women leaving jail to medications for opioid use disorder: Costs to implement pre-release telehealth and peer navigation services.

AIMS: Telehealth and peer navigation are feasible strategies for connecting women in the criminal-legal system with medications for opioid use disorder (MOUD), yet implementation costs are not well understood. This study conducted a microcosting analysis of two interventions for women leaving jail in Kentucky: pre-release, PreTreatment Telehealth with a MOUD provider (TH-Only) and PreTreatment Telehealth combined with peer navigation (TH+PN) through the Justice Community Opioid Innovation Network (JCOIN). METHODS: From the provider perspective, we estimated total start-up costs, total intervention costs, and average cost per participant. Women participating in the clinical trial were randomly assigned to TH-Only (n=299) or TH+PN (n=301). Start-up costs were incurred primarily in 2019 - 2020; intervention costs represent expenses in 2021 - 2023. Cost data were collected from study and agency financial records and interviews with research staff and analyzed using Microsoft Excel (version 16.90.2). RESULTS: Start-up costs were $36,320, comprising planning, meetings, travel, and supplies. The total cost of TH-Only was $60,767, representing 259 telehealth sessions with an average duration of 47 minutes. Total cost of TH+PN was $472,148 based on 270 telehealth sessions (48 minutes), 268 peer navigation (PN) sessions (30 minutes), and 12 weeks of PN support post-release per participant. Average cost per TH-Only participant was $235 and per TH+PN participant was $1,760. CONCLUSIONS: Telehealth may be a relatively low-cost approach for jails lacking on-site MOUD services. Although more costly, combining telehealth with PN may add value by supporting service continuity and facilitating linkage to treatment during the jail to community transition.

Humans↗

PubMed2026

Symptoms of Anxiety in Adults with ADHD: A Systematic Review and Meta-Analysis of Case-Control Studies.

OBJECTIVE: Research suggests there is a higher prevalence of anxiety in individuals with ADHD compared to those without ADHD. However, estimated prevalence rates vary greatly due to differences in methodologies used across studies. This study is the first meta-analysis investigating differences in anxiety measure scores between adults with and without ADHD, and possible moderators of this effect. METHOD: Our analysis included 58 studies that compared anxiety scores in adults with/without ADHD (N = 18,821; k = 112). RESULTS: The average effect size (Hedges's g) of anxiety scores in those with ADHD relative to controls was 0.77 (SE = 0.066); a medium effect. The only significant moderator was the type of comparison group used, with comparisons to non-clinical control groups (g = 0.954, SE = 0.08) yielding significantly larger effects than comparisons to clinical control groups (g = 0.437, SE = 0.09). None of the other moderator variables examined (Method of characterising ADHD, Anxiety Measure Type, Anxiety Measure Focus, Age or Gender) moderated the effect. There was some evidence of publication bias, therefore results should be interpreted with this in mind. CONCLUSION: Overall, this study indicates that ADHD is associated with higher levels of anxiety symptomology. This has important implications in the diagnosis and treatment of individuals presenting with ADHD or anxiety, including the consideration and screening of each of these conditions as potentially co-occurring with the other. Adaptions made to clinical practice in line with this would better support this population, improve symptom management and overall quality of life. Suggestions for future research are discussed.

Humans↗

PubMed2026

A 12-week, double-blind, quasi-randomized, placebo-controlled study to evaluate the efficacy and safety of Coleus forskohlii (Forcslim) on body weight loss.

BACKGROUND: Overweight and obesity have emerged as a global epidemic, significantly impacting human health. Traditional usage and growing scientific evidence suggest that Coleus forskohlii extract (Forcslim) may aid in reducing excess body weight and fat. This study aimed to evaluate the efficacy and safety of Forcslim supplementation in overweight individuals. METHODS: A quasi-randomized, double-blind, placebo-controlled clinical trial was conducted in 60 overweight subjects aged 20-70 years over a period of 12 weeks. The participants were assigned to receive either Forcslim or placebo. The key outcome measures included body weight, body mass index (BMI), body composition, and anthropometric parameters. Additionally, lipid profile parameters and safety markers (including metabolic, hepatic, and cardiovascular indicators) were assessed throughout the study duration. RESULTS: Compared to the placebo group, the Forcslim group showed significant reductions in waist circumference (-1.83 cm; p < 0.01) and body weight (-1.93 kg; p < 0.001). Significant improvements in anthropometric parameters were observed exclusively in the Forcslim group. Furthermore, triglyceride (TG) levels were significantly reduced (p < 0.01), while high-density lipoprotein (HDL) levels showed a significant increase (p = 0.001). No clinically significant changes were observed in metabolic markers, liver and muscle enzyme levels, heart rate, blood pressure, or reported adverse effects, indicating a favorable safety profile. CONCLUSIONS: Forcslim demonstrated significant anti-obesity effects, including reductions in body weight, waist circumference, and improvements in the lipid profile. These findings suggest that C. forskohlii extract supplementation may serve as a safe and effective alternative to synthetic anti-obesity drugs.

Humans↗

PubMed2026

ADAM10's combined influence on the diagnostic usefulness of IL 22, IL 10, IL-17 A, and IL-17D in autism spectrum disorders: Predicted role on gut leakiness as co-morbidity.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing global prevalence but a lack of reliable diagnostic biomarkers. Emerging evidence suggests that immune dysregulation, gut-brain axis dysfunction, and increased intestinal permeability play key roles in ASD pathophysiology. This study investigated the combined diagnostic value of ADAM10 and cytokines (IL-10, IL-22, IL-17 A, and IL-17D). Multivariable logistic regression produces an improved ROC curve that improves diagnostic accuracy over individual markers by combining numerous predictors into a single risk score (linear predictor). The technique, which frequently raises individual marker AUCs, entails modelling a binary result, calculating the probability, and visualizing ROC based on the projected probabilities. In this case-control study, plasma levels of ADAM10, IL-10, IL-22, IL-17 A, and IL-17D were measured in 37 male children with ASD and 37 age-matched controls. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curve analyses, including combined ROC models, were performed. ADAM10, IL-22, and IL-17 A levels were significantly reduced in children with ASD compared to controls, whereas IL-10 and IL-17D showed no significant differences. ADAM10, IL-17 A, and IL-22 demonstrated good diagnostic performance, with AUC values of 0.886, 0.855, and 0.812, respectively. In contrast, IL-10 and IL-17D showed poor discriminatory ability, with AUC values of 0.524 and 0.599, respectively. Combined ROC analysis markedly improved diagnostic accuracy, with all panels including ADAM10 achieving AUC values above 0.90, and some reaching as high as 0.988, with high sensitivity and specificity. The combination of ADAM10 with selected cytokines significantly enhances diagnostic performance compared to individual markers, supporting a link between immune dysregulation, barrier dysfunction, and gut permeability in ASD.

Humans↗

PubMed2026

Safety and efficacy of immune checkpoint inhibitors as a bridge to allogeneic hematopoietic stem cell transplantation in classical Hodgkin lymphoma: A systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for relapsed or refractory classical Hodgkin lymphoma (cHL); however, a substantial subset of patients ultimately requires allogeneic hematopoietic stem cell transplantation (allo-HCT) to achieve long-lasting disease control. The use of ICIs as a bridge to allo-HCT has therefore gained increasing clinical interest, though concerns persist regarding post-transplant complications and incompletely-defined safety profiles. Accordingly, this systematic review and meta-analysis was conducted to evaluate outcomes of ICIs administered prior to allo-HCT in cHL. Following PRISMA guidelines, a comprehensive literature search was conducted across online databases through January 2026. Eligible studies included observational designs reporting survival and transplant-related outcomes in cHL patients treated with ICIs followed by allo-HCT. Pooled proportions for overall survival, progression-free survival, non-relapse mortality, and graft-versus-host disease (GVHD) incidence were calculated using a random-effects model. Seven studies comprising 739 patients were included. Post-transplant survival outcomes were favorable, with high pooled estimates across timepoints. Transplant-related mortality remained low, with NRM rates consistently within an acceptable range through long-term follow-up. Acute GVHD was observed at a meaningful frequency, including a smaller subset of severe cases, while chronic GVHD occurred in approximately one-quarter of patients at follow-up. Overall, these findings suggest that ICI therapy prior to allo-HCT in cHL is associated with encouraging survival and disease control and does not appear to confer excessive non-relapse mortality, supporting its use as a feasible and effective bridging strategy, while underscoring the need for future prospective studies to clarify optimal timing, risk mitigation strategies, and patient selection.

Humans↗

PubMed2026

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗

PubMed2026

Transcranial Alternating Current Stimulation at 40 Hz Improves Social Functioning in Children With Autism Spectrum Disorder: A Randomized Clinical Trial.

BACKGROUND: Autism spectrum disorder (ASD) lacks rapid and effective interventions for its core social difficulties. The right temporoparietal junction (rTPJ), a critical hub for social cognition, together with gamma band abnormalities implicated in ASD, provides a promising neuromodulation target. METHODS: In this randomized, double-blind, sham-controlled trial, 47 children with ASD (39 male; mean [SD] age = 8.79 [2.71] years) were assigned to receive either 21 sessions of 40-Hz high-definition transcranial alternating current stimulation (tACS) targeting the rTPJ (3 sessions/day for 7 days) or sham stimulation, with assessments conducted at baseline, postintervention (week 1), and a 3-week follow-up (week 4). The primary outcome was change in Ohio State University Autism Rating Scale-DSM-5 (OARS-5) total scores. Secondary outcomes included the Aberrant Behavior Checklist-Second Edition, Social Responsiveness Scale-Second Edition, and Short Sensory Profile. Eye-tracking metrics during Frith-Happé animations were exploratory measures of theory of mind (ToM)-related social cognitive processing. RESULTS: The active group demonstrated significant improvements in OARS-5 total scores at week 1 (mean difference = -1.13, 95% CI [-1.78 to -0.47], p < .001) and week 4 (mean difference = -1.47, 95% CI [-2.20 to -0.74], p < .001). Improvements in selected behavioral and sensory domains were observed. Average fixation duration during ToM animations showed a significant group × time interaction. No serious adverse events occurred. CONCLUSIONS: These findings suggest that 40-Hz tACS targeting the rTPJ may be associated with rapid improvements in ASD symptom severity, particularly social functioning, in children with ASD, while being well tolerated. Clinical significance requires further evaluation.

Humans↗

PubMed2026

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗

PubMed2026

Efficacy of a high-frequency repetitive transcranial magnetic stimulation for craving reduction in adolescents with gaming disorder: a 4-week randomized control trial with 24-week follow-up.

BACKGROUND: With the widespread popularity of online gaming, gaming addiction has come under scrutiny. While there is ongoing research on the diagnosis and treatment of gaming disorder among adolescents, the clinical robustness and reliability of intervention strategies remain uncertain. METHODS: A 4-week, double-blind, randomized, sham-controlled clinical trial was conducted to evaluate the efficacy of noninvasive, high-frequency repetitive transcranial magnetic stimulation (rTMS) in alleviating psychological craving in adolescents diagnosed with gaming disorder. Sham rTMS was administered to the control group using the tilted-coil method. Both groups of participants were treated with SSRI medications. A total of 80 adolescents with gaming disorder participated in this study, and 73 ultimately completed the 24-week follow-up. The primary outcome was the change in craving levels before and after the rTMS intervention, as assessed by the Visual Analogue Scale (VAS). Secondary outcomes included changes in anxiety and depression levels before and after the intervention, as assessed by the HAMA and HAMD. RESULTS: We assessed levels of psychological craving, anxiety, and depression among adolescents with gaming disorder at baseline, after completing a 4-week intervention, and at a 24-week follow-up post-intervention. Our repeated-measures MANOVA results, adjusted for course variables, revealed a significant main effect of rTMS intervention on psychological craving levels in adolescents addicted to online games (F(11, 781) = 11.238, P < 0.001, partial η² = 0.142), as well as significant main effects on time (F(11, 781) = 6.809; P < 0.001, partial η² = 0.091) and group effects (F(1, 71) = 26.707, P < 0.001, partial η² = 0.282). In addition, repeated-measures ANOVA results showed significant time effects for anxiety (F(2, 142) = 20.747, P < 0.001, partial η² = 0.234) and depression levels (F(2, 142) = 22.277, P < 0.001, partial η² = 0.285) among adolescents with gaming disorder, with nonsignificant between-group effects and no intergroup interaction. In the active stimulation group, changes in psychological craving levels after 4 weeks of treatment were significantly and positively correlated with changes in anxiety levels after 4 weeks of treatment in adolescents addicted to online games (r = 0.335, P < 0.05). CONCLUSION: Our findings indicate that high-frequency rTMS targeting the left dorsolateral prefrontal cortex may be a promising approach for reducing psychological craving in adolescents with gaming disorder. TRIAL REGISTRATION: ChiCTR2500102979 in chictr.org.cn, registered on May 22, 2025.

Humans↗