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PubMed2026

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2 × 3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time × group interaction was detected for any ES biomarker, including 2-AG (F(2,88) = 0.17, p = 0.844) and AEA (F(2,88) = 1.20, p = 0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference + 81.6 m at 12 weeks (F(2,78) = 7.88, p = 0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78) = 2.83, p = 0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗

PubMed2026

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans↗

PubMed2026

Effectiveness of Mobile-Delivered Exercise and Yoga Programs on Depressive Symptom Reduction in Employees: Randomized Controlled Trial.

BACKGROUND: Mental health challenges such as stress and depression are prevalent among employees. Mobile health platforms that deliver exercise or yoga interventions offer a promising approach to improve mental health outcomes in this population. OBJECTIVE: This study aimed to assess the effectiveness of 12-session adaptive moderate-intensity exercise and yoga programs delivered via a motion-detecting digital platform in reducing stress and depressive symptoms among employees. METHODS: This was an unblinded, 3-arm, parallel-group, randomized controlled trial conducted at Seoul National University Bundang Hospital and Boramae Medical Center between November 2023 and January 2024. Eligible participants were full-time employees. Seventy-five participants were randomly assigned to an exercise, a yoga, or a cognitive behavioral therapy-based self-care control group using computer-generated randomization. The exercise and yoga groups engaged in motion-detecting, adaptive physical activity training, whereas the control group accessed mobile-based, self-directed stress management educational materials. The intervention was largely automated, with no individualized therapeutic guidance provided. Allocation was concealed until trial entry. All recruitment and outcome assessments were conducted in person at the hospitals. The primary outcomes were perceived stress and depressive symptoms, whereas the secondary outcomes included posttraumatic stress, insomnia severity, cognitive stress response, occupational stress, and burnout. Physiological outcomes were assessed using heart rate variability and electroencephalography. Measurements were collected at baseline, immediately after the intervention, and at 4-week follow-up. Data were analyzed using a multivariate linear model to evaluate the main effects of time, group, and time×group interactions. RESULTS: Of the 75 randomized participants (exercise: n=24, 32%; yoga: n=25, 33.3%; and control: n=26, 34.7%), 71 (94.7%) who completed at least 9 of the 12 sessions (≥40 min each) were included in the outcome analysis (exercise: n=21, 29.5%; yoga: n=24, 33.8%; and control: n=26, 36.6%). For the coprimary outcomes, the group×time interaction for depressive symptoms (Patient Health Questionnaire-9) approached but did not reach the Bonferroni-corrected threshold (F4,136=2.71; P=.03; adjusted α=.025); however, planned pairwise comparisons revealed significantly greater improvement in the yoga group compared to the control group at 4-week follow-up (β=-3.67; adjusted P<.001). For the Perceived Stress Scale, the interaction was not significant (P=.29), although a significant main effect of time (P<.001) indicated overall stress reduction across all groups. For secondary outcomes, a significant group×time interaction was found for the Cognitive Stress Responses Scale (P=.003), indicating differential trajectories of improvement. The yoga group showed a consistent linear decrease, whereas the exercise group showed immediate but less sustained gains. CONCLUSIONS: Digitally delivered adaptive yoga programs demonstrated superior and sustained improvements in depressive symptoms and Cognitive Stress Responses Scale scores compared with the active cognitive behavioral therapy-based self-care control group. However, the exercise program showed more modest and less sustained effects, warranting further investigation using larger samples.

Adult↗

PubMed2026

Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

BACKGROUND: Patients undergoing acoustic neuroma (AN) surgery often experience postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. METHODS: In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were assigned to esketamine (n = 42) or placebo (n = 42). The esketamine cohort received a continuous intravenous infusion of esketamine at 0.2 mg·kg-1·h-1 during anesthesia, followed by 1 mg·kg-1 esketamine as an adjuvant in patient-controlled intravenous analgesia (PCIA). The placebo group received saline. The primary outcome was the incidence of depression on postoperative day (POD1), defined as a Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) score > 7. RESULTS: Seventy-seven patients completed the study (39 in the esketamine group, 38 in the placebo group). Esketamine significantly reduced the incidence of depression at POD1 (7.7% versus 31.6%; relative risk 0.24, 95% CI: 0.08-0.80, p = 0.008) and POD3 (0.0% versus 15.8%, relative risk 0.00, 95% CI: 0.00-0.47, p = 0.031) compared with placebo. The incidences of anxiety on POD1 and 3 and sleep disturbances on POD1 were also significantly reduced (p < 0.05). Notably, no significant differences were observed between the two groups in terms of immune function, postoperative pain scores, or intraoperative morphine equivalent. Adverse events did not differ between the groups. CONCLUSION: Perioperative sub-anesthetic esketamine reduced postoperative depression and anxiety, and improve sleep quality after AN surgery, without significant effects on early immune function or acute postoperative analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400084537.

Humans↗

PubMed2026

Psychotherapy vs antidepressants in heart failure: Impact of adherence.

BACKGROUND: Depression affects nearly half of patients with heart failure (HF), which is associated with increased morbidity and reduced health-related quality of life (HRQoL). This secondary per-protocol analysis of a previously published randomized trial evaluated the behavioral activation (BA) versus antidepressant medication (MEDS) among patients with depression and HF who adhered to study interventions. METHODS: This analysis is based on a pragmatic randomized comparative-effectiveness trial conducted from 2018 to 2022, with a 1-year follow-up. 416 participants diagnosed with HF and a DSM-5 depressive disorder were randomized to BA or MEDS, and the current analysis examined outcomes according to treatment adherence. OUTCOMES: The primary outcome was depressive symptom severity (PHQ-9) at 6 months, and the secondary outcomes were physical and mental HRQoL (SF-12v2-PC and SF-12v2-MC, respectively) and HF-specific HRQoL (Kansas City Cardiomyopathy Questionnaire; KCCQ) overall and clinical scores (KCCQ-OS and KCCQ-CS), at 3, 6, and 12 months. High adherence was defined as completion of >75-100% of intervention components. Overall adherence rates were similar between BA and MEDS. At 6 months, among patients with >75-100% adherence who followed treatment as directed in both arms, BA was associated with higher Mental HRQoL (SF-12v2-MC: 5.22; 95% CI: 0.72 to 9.72; p = 0.023) and higher HF-specific HRQoL (KCCQ-OS: 16.08; 95% CI: 7.20 to 24.97; p < 0.001); (KCCQ-CS: 16.04; 95%CI: 7.05 to 25.02; p < 0.001) compared to MEDS. There were no significant differences in depressive symptoms or physical HRQoL at 6 months. INTERPRETATION: Both BA and MEDS were equally effective treatments for depression in HF. However, among highly adherent patients, BA was associated with greater improvements in mental and HF-specific HRQoL than MEDS. FUNDING/SUPPORT: The study was funded by PCORI Award Number: 2017C2-7716.

Humans↗

PubMed2026

Perioperative Depression and Anxiety Care in Older Patients: A Randomized Clinical Trial.

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking. OBJECTIVE: To evaluate a perioperative intervention to optimize mental health. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety and Depressive Symptom (PHQ-ADS) scale. A total of 3159 patients were screened for eligibility, with 1518 ineligible, 1079 declining participation, and 236 excluded for other reasons. A total of 326 patients were enrolled and randomized (1:1), with 20 excluded after surgery cancelation. INTERVENTION: Participants were assigned to receive a perioperative intervention combining psychological management and pharmacologic optimization or enhanced usual care (materials for self-managing symptoms). MAIN OUTCOMES AND MEASURES: The primary outcome was change in PHQ-ADS score from baseline to 3 months after surgery. Other outcomes included persistent postsurgical pain, delirium, falls, quality of life, patient satisfaction, length of stay, and rehospitalizations. Implementability was evaluated through semistructured interviews and reach, acceptability, feasibility, appropriateness, and fidelity measures. RESULTS: A total of 306 older adults were included in analysis (mean [SD] age, 68.5 [6.1] years; 209 [68.3%] female; 153 randomized to intervention and 153 randomized to enhanced usual care): 102 cardiac, 100 oncologic, and 104 orthopedic patients. Participants' mean (SD) baseline PHQ-ADS score was 18.5 (7.4). At 3 months, there was a significant decrease in PHQ-ADS scores in the intervention group compared with the enhanced usual care group (mean difference, 2.20; 95% CI, 0.16-4.24; P = .03). Effects varied by surgical subgroups (oncologic patients: mean difference, 4.93; 95% CI, 1.51-8.36; P = .005; cardiac patients: mean difference, 2.68; 95% CI, -0.98 to 6.35; P = .15; and orthopedic patients: mean difference, -1.11; 95% CI, -4.62 to 2.40; P = .54). Patients and interventionists perceived the intervention as appropriate, with high-fidelity delivery and broad reach across the target population. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, psychological management and pharmacologic optimization reduced anxiety and depression in older adults undergoing surgery. Future studies should assess reproducibility and determine which patients benefit most. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT05575128, NCT05685511, and NCT05697835.

Humans↗

PubMed2026

New Data Relevant to Treating Substance Use Disorders, Bipolar Disorder, and Pediatric Anxiety Disorders.

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Anxiety Disorders↗

PubMed2026

Music therapy in artificial insemination by husband: Effects on psychological distress and clinical pregnancy rate.

BACKGROUND: Infertility treatment can be psychologically burdensome. Evidence on music listening during artificial insemination by husband (AIH) remains limited. We evaluated whether a standardized periprocedural music intervention reduced psychological distress and explored its association with clinical pregnancy. METHODS: In this single-center, open-label randomized trial, 254 women undergoing AIH were allocated 1:1 to routine care or routine care plus two 30-minute music-listening sessions, immediately before and after AIH. The prespecified primary outcome was the continuous 21-item Depression Anxiety Stress Scales (DASS-21) score at follow-up; clinical pregnancy was secondary. DASS-21 was completed at baseline and at day 35 after AIH. Clinical pregnancy was assessed by ultrasonography at days 30 to 35. RESULTS: Continuous DASS-21 anxiety, depression, and stress scores did not differ between groups after adjustment for baseline scores (all P ≥ .868). Absolute postintervention differences were 0.01 point or less for anxiety and depression and 0.08 point for stress, indicating neither statistical nor clinically meaningful improvement. Clinical pregnancy occurred in 34/127 participants (26.77%) in the intervention group and 14/127 (11.02%) in the control group (exploratory secondary outcome; P = .001). CONCLUSION: The intervention did not improve the primary psychological outcome. The higher clinical pregnancy rate is hypothesis-generating because the trial was not powered for pregnancy, the proposed psychological mechanism was not demonstrated, and nonspecific attention and other unmeasured factors cannot be excluded. Replication using an attention-matched control, immediate state-anxiety and physiological measures, participant-preference assessment, and live-birth follow-up is required.

Humans↗

PubMed2026

[Efficacy and safety of acute-phase transcutaneous auricular vagus nerve stimulation for herpes zoster-related pain in middle-aged and elderly patients with comorbid depression and anxiety].

Objective: To evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) during the acute phase in middle-aged and elderly patients with herpes zoster (HZ) comorbid depressive and anxiety states. Methods: This was a randomized controlled trial. Forty middle-aged and elderly patients with acute-phase HZ who attended the Department of Dermatology at Xuanwu Hospital, Capital Medical University, from June 2024 to June 2025 were enrolled and randomly assigned in a 1∶1 ratio using a random number table to receive either taVNS (n=20) or sham stimulation (n=20) for 5 consecutive days. Both groups received antiviral therapy and on-demand rescue analgesia. Pain, anxiety/depression, and sleep quality were evaluated using the Visual Analog Scale (VAS), the 4-item Patient Health Questionnaire (PHQ-4), and the Insomnia Severity Index (ISI), respectively. The primary outcome was the incidence of subacute pain at 30 days post-rash onset. Secondary outcomes included cumulative analgesic consumption at 1 and 2 weeks after treatment, the changes from baseline (Δ values) in PHQ-4 and ISI scores at 2 weeks, and the incidence of postherpetic neuralgia (PHN) at 90 days post-rash onset. Results: In the taVNS group, 7 patients (35%) were female, with a mean age of (64.1±9.7) years; in the sham group, 10 patients (50%) were female, with a mean age of (61.5±8.5) years. There were no statistically significant differences between the two groups in baseline VAS, PHQ-4, or ISI scores (all P>0.05). The incidence of subacute pain was significantly lower in the taVNS group than in the sham group [5% (1/20) vs 35% (7/20), RD=-30.0% (95%CI:-52.1%--4.9%); RR=0.14 (95%CI: 0.02-1.06); P=0.044]. At 2 weeks after treatment, the Δ values of PHQ-4 and ISI in the taVNS group were significantly greater than those in the sham group. The proportion of patients taking Lofentadine and the cumulative Lofentadine consumption at weeks 1 and 2 were both lower in the taVNS group than in the sham group (all P<0.05). No serious adverse events occurred in either group, and the difference in PHN incidence between groups was not statistically significant (P>0.05). Conclusions: Acute-phase taVNS appears to be feasible and safe in middle-aged and elderly patients with HZ and comorbid depressive and anxiety, effectively reducing subacute pain and improving emotional and sleep outcomes.

Humans↗

PubMed2026

Effects of Digital Mental Health Screening Alone and With the Online MINDBODYSTRONG CBT-Based Program on Burnout, Depression, Anxiety, Healthy Behaviors, and Suicidal Ideation in at-Risk Nurses at 3- and 6-Months Post-Intervention: An RCT.

BACKGROUND: Burnout and mental distress among nurses are global public health epidemics that adversely affect nurse well-being and healthcare quality. Evidence-based, scalable mental health interventions are urgently needed. AIMS: To evaluate the 3- and 6-month outcomes of a randomized controlled trial (RCT) comparing a psychologically safe, digital mental health screening and referral program alone versus the same screening and referral program combined with the video-based online MINDBODYSTRONG (MBS) cognitive behavioral therapy (CBT)-based skills-building program among nurses at risk for mental distress. METHODS: 501 nurses were recruited from professional organizations and healthcare systems across the United States by email and randomized to either mental health screening and referral (standard care) or standard care plus the MBS cognitive behavioral skills-building intervention (the intervention). All study activities were conducted remotely. Follow-up surveys administered at 3- and 6-months assessed anxiety, depression, suicidal ideation, burnout, healthy lifestyle beliefs, and healthy lifestyle behaviors using valid and reliable scales. RESULTS: Compared with the screening and referral only group, participants in the intervention group had greater reductions in anxiety and depression and significantly greater increases in healthy lifestyle beliefs and behaviors at 3 and 6 months post-intervention. After controlling baseline risk, the intervention group had a lower risk of suicidal ideation than the screening and referral group at 3 months (relative risk ratio [RRR] = 0.717; 95% CI: 0.320-1.606) and 6 months (RRR = 0.329; 95% CI: 0.101-1.072). The intervention group also had a significantly lower risk of burnout at 6 months (RRR: 0.698, 95% CI: 0.528, 0.929, p = 0.012). Nurses who completed more MBS sessions had less suicidal ideation at 6 months and those who completed more MBS skills-building activities had less burnout at 3 and 6 months. LINKING ACTION TO EVIDENCE: Integrating psychologically safe mental health screening combined with the scalable online CBT-based intervention, MBS, can produce sustained improvements in burnout, mental health symptoms, including suicidality, and healthy lifestyle beliefs and behaviors among nurses experiencing mental distress.

Humans↗

PubMed2026

Comparison of the clinical efficacy, safety and EEG functional connectivity changes between 18-Hz rTMS and iTBS of accelerated dTMS treatment for major depressive disorder: a randomized controlled trial.

Although the antidepressant efficacy of 18-Hz deep transcranial magnetic stimulation (dTMS) has been validated, its prolonged treatment duration has considerable limitations for treatment capacity and patient adherence. Therefore, novel short-course protocols such as accelerated dTMS and intermittent theta burst stimulation (iTBS) present promising alternative options. Here we addressed the question of whether iTBS of accelerated dTMS achieves comparable therapeutic and electrophysiological effects to accelerated dTMS with the conventional 18-Hz rTMS protocol in patients with major depressive disorder (MDD). In a randomized controlled trial (n = 73), participants received either 18-Hz rTMS of accelerated dTMS (rTMS-dTMS group), iTBS of accelerated dTMS (iTBS-dTMS group), or pharmacotherapy alone (drug group). Both dTMS protocols were administered twice daily for 10 days targeting the left lateral prefrontal cortex including the dorsolateral region. Results showed that Hamilton Depression Rating Scale (HAMD) score of the iTBS-dTMS group decreased significantly from 22.5 ± 3.7 before treatment to 8.2 ± 4.1 after treatment (t = 15.900, p < 0.001). HAMD score of the rTMS-dTMS group decreased significantly from 21.3 ± 2.9 before treatment to 8.0 ± 3.8 after treatment (t = 17.232, p < 0.001). The drug group also exhibited significantly improved patients' mood symptoms, and the HAMD score decreased from 24.7 ± 6.8 to 14.0 ± 5.0 (t = 6.363, p < 0.001). The treatment response rate was 85.7% in the iTBS-dTMS group and 76.9% in the rTMS-dTMS group, which was much higher than that of the drug group (42.1%). The remission rate was 50.0% in the iTBS-dTMS group and 42.3% in the rTMS-dTMS group, which was significantly higher than 10.5% of the drug group. We demonstrate here that both accelerated dTMS protocols significantly reduced HAMD scores, improved the response rates, and remission rates, outperforming pharmacotherapy alone. Resting-state EEG analysis further revealed unique frequency-specific functional connectivity (FC) modulation effects: the rTMS-dTMS group primarily exhibited weakened alpha-band functional connectivity within the fronto-occipital, fronto-temporal and fronto-central networks after treatment, whereas the iTBS-dTMS group predominantly demonstrated reduced theta-band functional connectivity within the fronto-parietal, fronto-occipital and fronto-temporal pathways after treatment. These findings indicate that iTBS of accelerated dTMS demonstrates comparable efficacy and tolerability to 18-Hz rTMS of accelerated dTMS, whilst inducing treatment-specific network-level neurophysiological alterations. In the rTMS-dTMS group, relative changes in FC between the frontal and temporal/precentral regions showed significant negative correlation with HAMD score reduction rates, while relative changes in FC between the frontal lobe and parietal lobe showed a significant positive correlation with the rate of HAMD score reduction for the iTBS-dTMS group. This study revealed novel mechanisms by which accelerated dTMS protocols modulate brain networks, providing evidence for the clinical application of accelerated iTBS-dTMS as an efficient, evidence-based treatment for MDD.

Humans↗

PubMed2026

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n = 75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p = 0.02 to p < 0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans↗

PubMed2026

Effectiveness of symptom map-based education in the management of premenstrual syndrome: a randomized controlled trial.

PURPOSE: To evaluate the effectiveness of a symptom map-based educational intervention for the non-pharmacological management of premenstrual syndrome (PMS), with a focus on symptom reduction among women with differing baseline symptom severity. METHODS: This randomized controlled study was conducted between May and December 2024. A total of 110 women meeting diagnostic criteria for PMS were randomly assigned to an intervention group (n = 55) or a control group (n = 55) using block randomization, and 101 participants completed follow-up assessments. The intervention comprised structured education based on a PMS symptom map and evidence-based self-care strategies. Outcomes included PMS symptom severity (Premenstrual Syndrome Scale), pain intensity (Visual Analog Scale), psychological symptoms (Depression Anxiety Stress Scale-21), and PMS-specific life satisfaction. CLINICAL TRIAL REGISTRATION: NCT06585475. RESULTS: Compared with the control group, women in the intervention group reported significantly lower pain (adjusted mean 4.21 vs. 6.81, p < .001) and stress levels (8.54 vs. 12.03, p < .001) at follow-up. The intervention was particularly effective in reducing PMS symptom severity and depressive symptoms among participants with higher baseline symptom burden. Improvements in PMS-specific life satisfaction were observed, with reductions in depressive symptoms contributing to this effect. CONCLUSION: A symptom map-based educational intervention is a clinically applicable, non-pharmacological approach for PMS management. This structured education appears especially beneficial for women with more severe baseline symptoms and may be integrated into routine gynecological care to support individualized symptom management.

Humans↗

PubMed2025

Mindfulness and Sex Education for Sexual Dysfunction in Breast Cancer Survivors: Mediators and Moderators of Treatment Outcome.

Mindfulness-based cognitive therapy (MBCT) and supportive-expressive sex education therapy (STEP) are effective group treatments for sexual dysfunction after breast cancer (BrCa). We explored mediators and moderators of outcomes following the 8-week groups. BrCa survivors (n = 116, mean age = 49.9 ± 9.5) were randomized to group and completed measures before, immediately after, and 6 months after treatment. Mediators assessed were changes in depression, chronic pain acceptance, pain catastrophizing, and trait mindfulness. Potential moderators included age, treatment expectations, baseline mental health, cancer treatment duration, use of chemotherapy, and adjuvant endocrine therapy. Longitudinal mediation and moderation were assessed using linear mixed models. Increases in pain acceptance mediated improvements in sexual desire and reductions in both sexual distress and vaginal pain. Decreases in pain catastrophizing mediated improvements in sexual distress. Higher expectations for treatment led to greater reductions in sexual distress. Those with low baseline anxiety showed greater improvements in desire and distress. Low baseline depression predicted greater improvements in desire, but only in the STEP arm. Older STEP participants improved significantly more than younger STEP participants. Cancer-related treatment variables, and the impact of adjuvant endocrine therapy, had differential effects on outcomes based on the treatment arm of the study. In conclusion, treatments aimed at improving pain acceptance and pain catastrophizing are likely to promote improvements in sexual health among BrCa survivors, and factoring in patients' expectations about treatment improvements, depression and anxiety, age, duration of cancer treatment, chemotherapy, and adjuvant hormonal therapy may help to guide treatment recommendations for sexual dysfunction.

Humans↗

PubMed2026

Understanding specificity in immune-brain pathways: A systematic review of differential associations between individual cytokines and brain structure and function measured through magnetic resonance imaging in humans.

Research shows that cytokines are associated with psychiatric disorders, including major depression, and multiple aspects of brain structure and function. Accumulating data suggest that different cytokines may have unique profiles of biological activity, particularly in their neuromodulatory roles, but it is currently unclear whether they have unique associations with specific neural circuits in humans. In this paper, we systematically review magnetic resonance imaging studies conducted with depressed or healthy control human participants under age 65 that examine associations between peripheral cytokines and brain structure and function, with the goal of evaluating evidence for the specificity of these cytokine-brain associations. We find that across multiple measures of brain structure and function, the majority of studies reviewed reported unique associations between individual cytokines and brain outcomes. A synthesis of findings across studies also suggests a preliminary hypothesis of specific associations of interleukin-6 levels in circulation with the default mode network and tumor necrosis factor-alpha with the salience network, which could be tested in future research. We conclude the review with future directions for research that can strengthen understanding of these associations.

Humans↗

PubMed2026

Brief Report: Beyond Testing: Exploring the Psychosocial Impact of HIV Self-Testing Among Ugandan Gender-Diverse Sex Workers.

BACKGROUND: The psychosocial effect of HIV self-testing (HIVST) on sex workers' self-esteem, depression, alcohol misuse, perceived sex work stigma, and empowerment remains poorly characterized. We hypothesized that HIVST would reduce sex work stigma and improve these psychosocial outcomes by enabling private, autonomous testing and reducing exposure to stigmatizing healthcare encounters. SETTING: Kampala, Uganda. METHODS: We conducted a secondary analysis of the Empower study (NCT03426670), an open-label randomized trial in which 117 cisgender female, transgender female, and cisgender male sex workers were assigned 1:1 to monthly HIVST plus quarterly clinic-based testing, or to quarterly clinic-based testing alone, and followed for 12 months. Self-esteem (Rosenberg Self-Esteem Scale), depressive symptoms (PHQ-2), alcohol misuse (RAPS4), perceived sex work stigma (adapted Female Sex Worker Stigma Scale), and empowerment were assessed quarterly. Mixed-effects regression models, adjusted for baseline values, evaluated intervention effects. RESULTS: Data from 117 participants were analyzed, including 7 early disenrollments. Over 12 months, HIVST participants reported significantly lower perceived sex work stigma than standard of care participants (β = -0.38, P = 0.04; monthly reduction P = 0.003), although the rate of decline did not differ significantly between arms (interaction P = 0.08). Self-esteem and depressive symptoms improved in both arms, with no between-arm differences (interaction P = 0.41 and 0.32). Alcohol misuse and empowerment showed no significant arm differences. CONCLUSION: HIVST may reduce sex work stigma without adverse psychosocial effects, supporting its integration into combination HIV prevention for gender-diverse sex workers in sub-Saharan Africa.

Humans↗

PubMed2026

Effects of low-dose esketamine on early quality of recovery following minimally invasive esophagectomy: a multicenter, randomized controlled study.

BACKGROUND: Patients undergoing minimally invasive esophagectomy (MIE) frequently experience moderate-to-severe postoperative pain and anxiety-depressive symptoms, compromising postoperative quality of recovery (QoR). Esketamine is a promising adjunct for analgesia and anxiolysis; however, the effect of low-dose esketamine on patient-centered recovery outcomes in MIE remains unclear. METHODS: In this double-blinded, multicenter randomized controlled trial, patients scheduled for elective McKeown esophagectomy were allocated to esketamine (0.25 mg/kg loading dose and 0.125 mg/kg/h continuous infusion during surgery) or placebo (equivalent volume and rate of saline). The primary outcome was the QoR-15 score on postoperative day (POD) 2. Secondary outcomes included QoR-15 scores on POD 1, 3, 7 and 30. Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A) and Depression Subscale (HADS-D) scores, numeric rating scale (NRS) pain scores, and the Brief Pain Inventory (BPI) scores on POD 1 to 3, and safety evaluations. RESULTS: A total of 198 patients were analyzed (esketamine, n = 98; placebo, n = 100). Intraoperative esketamine significantly improved QoR-15 scores on POD 2 (116.9 ± 9.4 vs. 110.2 ± 9.8, p < 0.001) and POD 3 (123.6 ± 7.2 vs. 116.8 ± 8.4, p < 0.001) compared with placebo. HADS-A and HADS-D scores were lower in the esketamine group on POD 1 to 3 (all p < 0.001). Additionally, esketamine recipients reported significantly lower NRS scores at rest and during movement and BPI scores for pain severity and pain interference items (all p < 0.001). There were no significant between-group differences in safety outcomes. CONCLUSIONS: Intraoperative low-dose esketamine improved early, patient-reported recovery after MIE by enhancing analgesia and reducing postoperative anxiety and depression without increasing adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Register (identifier: ChiCTR2400088916).

Humans↗