Digital Cognitive Behavioral Therapy for Older Adults With Symptoms of Depression: Feasibility Cohort Study

Background: Depressive symptoms are common among older adults and can significantly impact their quality of life. However, many older adults face barriers to accessing psychological treatment. Internet-based cognitive behavioral therapy (iCBT) is a promising alternative to face-to-face treatments, but its feasibility among older adults has been less extensively studied than in adult populations. Objective: This study evaluated the feasibility of guided iCBT for adults aged 55 years and older with mild to moderate depressive symptoms recruited from the general population. Methods: This study is a feasibility study with a single-group, pretest-posttest design (n=21), in which all participants received guided iCBT for 8 weeks. Assessments were conducted at baseline (T0) and after the intervention (T1). The primary outcome was feasibility, conceptualized as satisfaction, usability, engagement, and uptake of iCBT. Secondary outcome measures included depression severity, working alliance, and technical alliance. Results: Participants were mostly highly educated (13/21, 61.9%), female (18/21, 85.7%), had an average age of 59.85 (SD 4.19; range 55-68) years, and reported moderate digital literacy. Feasibility outcomes indicated high satisfaction and engagement and moderate usability. Working alliance was rated as good by both participants and coaches, and technical alliance was rated as moderate by the participants. There was a nonsignificant modest decrease in depressive symptoms (Cohen <i>d</i>=0.47). Of the 20 participants who started the intervention, all completed the first 2 modules, but completion declined across the remaining 6 modules, with only 1 (5%) participant completing all modules. Conclusions: This study found that guided iCBT has the potential to be a feasible option for older adults experiencing depressive symptoms, with participants reporting generally positive satisfaction, moderate engagement, and a moderate therapeutic bond with their coaches. However, below-average usability ratings and a moderate technical alliance suggest that some aspects of the platform require improvement. Future research should focus on improving usability and adherence, as well as testing the intervention in a larger and more diverse population.

Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis

Treatment-resistant depression (TRD) remains a major clinical challenge. Intranasal esketamine, used adjunctively with an oral antidepressant, has been evaluated in randomized trials, but uncertainty persists regarding the magnitude and consistency of benefit, durability, and key harms. This systematic review and meta-analysis included randomized controlled trials comparing intranasal esketamine plus an oral antidepressant versus placebo nasal spray plus the same oral antidepressant in TRD. Acute induction (≈4 weeks) and maintenance randomized-withdrawal phases were analyzed separately. Depression outcomes were assessed primarily using the Montgomery–Åsberg Depression Rating Scale (MADRS), and functional outcomes using the Sheehan Disability Scale (SDS). Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2.0. Random-effects models pooled mean differences (MD) for continuous outcomes, risk ratios (RR) for binary outcomes, and hazard ratios (HR) for relapse prevention. Certainty of evidence was rated using GRADE. From 1,518 records, nine reports representing six unique RCTs (1,836 participants) were included. Four acute induction RCTs (n=937) showed greater symptom reduction at day 28 with esketamine (MADRS MD −2.99, 95% CI −5.10 to −0.89; I²=48.5%). Rapid improvement was evident by day 2 (MD −3.25, 95% CI −4.65 to −1.85). Esketamine increased day-28 response (RR 1.44, 95% CI 1.20–1.74) and remission (RR 1.52, 95% CI 1.20–1.92), corresponding to approximately +154 responders and +106 remitters per 1,000 patients, respectively, based on pooled control risks. Functioning improved (SDS MD −1.70, 95% CI −2.61 to −0.79). Two maintenance randomized-withdrawal RCTs (n=899) demonstrated reduced relapse risk with continued esketamine (HR 0.51, 95% CI 0.42–0.62; I²=0%). In acute induction, esketamine increased any treatment-emergent adverse event (TEAE) (RR 1.37, 95% CI 1.25–1.50) and discontinuation due to adverse events (RR 2.68, 95% CI 1.35–5.29), with notable increases in dissociation (RR 7.33, 95% CI 4.49–11.98) and blood pressure increased events (RR 3.96, 95% CI 2.24–7.01). Maintenance TEAE rates were similar between groups (RR 1.07, 95% CI 0.99–1.17). Intranasal esketamine plus an oral antidepressant provides rapid, modest acute improvement and reduces relapse risk during maintenance among stabilized responders/remitters, but increases acute adverse events, supporting use within supervised care and individualized benefit–risk assessment.

Exercise interventions are most consistently supported for depressive disorders: an umbrella review of diagnosed depressive and anxiety disorders

BackgroundExercise is increasingly discussed as part of lifestyle-based and multimodal care for mood and anxiety disorders, but review-level evidence often mixes formally diagnosed clinical populations with symptom-defined or medically mixed samples.MethodsWe conducted an umbrella review of systematic reviews, meta-analyses, and network meta-analyses of structured exercise interventions for adults with depressive or anxiety disorders. Six databases were searched from inception to 1 March 2026. Primary outcomes were depressive and anxiety symptom severity, remission, and response; secondary outcomes were acceptability and tolerability. Review quality was appraised with AMSTAR 2, and primary-study overlap was quantified with corrected covered area (CCA), including overall and symptom-cluster analyses. The synthesis was designed to summarize review-level credibility and clinical interpretability rather than to generate a second-order pooled efficacy estimate.ResultsNine reviews met eligibility criteria; four supplied directly extractable primary overall review-level estimates for core psychiatric symptom outcomes. AMSTAR 2 appraisal rated one review as high, three as low, and five as critically low. Recalculated overall overlap was slight (112 primary-study occurrences, 89 unique primary studies; CCA = 3.23%), although cluster-level analyses identified localized redundancy, particularly within anxiety-disorder-specific reviews. In major depressive disorder, one clinically focused review reported a large reduction in depressive symptoms for aerobic exercise versus non-exercise comparators (Hedges’ g = -0.79, 95% CI -1.00 to -0.57; I² = 21%). Across diagnosed depressive and/or anxiety disorders, broader review-level estimates also favored exercise for depressive symptoms (SMD = -0.97, 95% CI -1.28 to -0.66) and anxiety symptoms (SMD = -0.66, 95% CI -1.09 to -0.23), but heterogeneity was high. Anxiety-disorder-specific evidence was less secure: the primary DSM-IV anxiety-disorder pooled estimate showed no clear benefit over selected controls (SMD = 0.02, 95% CI -0.20 to 0.24). Acceptability estimates were close to null, and adverse-event reporting was too sparse to support confident safety conclusions.ConclusionExercise is best supported as an adjunctive, patient-centered component of care for depressive disorders. Anxiety-disorder-specific efficacy remains uncertain when comparator rigor, diagnostic heterogeneity, and localized overlap are considered, and safety reporting needs substantial improvement.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261364264.

Health outcomes across socioeconomic strata B, C, and DE among Brazilian adults living in moderate social vulnerability

ObjectivesThis study examined whether socioeconomic status was associated with anxiety symptoms, depressive symptoms, BMI, waist-to-hip ratio, and quality of life among Brazilian adults living in areas of moderate social vulnerability. In addition, we described anxiety and depressive symptoms, BMI and waist-to-hip ratio, and quality of life in individuals living in moderate social vulnerability.MethodsThis is a cross-sectional study. In a socially vulnerable cohort, interviews captured demographics, comorbidities, medications, anxiety and depressive symptoms, and quality of life, followed by measurement of anthropometric characteristics.ResultsAmong 299 socially vulnerable adults, 8% had moderate–severe depressive symptoms and 7% had moderate–severe anxiety symptoms; ~50% showed increased risk of cardiometabolic diseases (i.e., waist-to-hip ratio greater or equal to 0.90 for men and 0.85 for women, respectively). Poor quality of life affected 4–12% across domains. Mental health, anthropometrics (waist-to-hip ratio, BMI), increased risk of cardiometabolic diseases and quality of life in physical, social and environmental domains did not differ by socioeconomic status (B, C, DE; all P>0.05). Poor psychological quality of life was more frequent among participants in higher socioeconomic status (B: 8%; C: 6%; DE: 4%, P = 0.0157). Linear regression analyses showed no statistically significant differences across socioeconomic status in depressive symptoms, anxiety symptoms, BMI, waist-to-hip ratio, or quality of life scores in any domain (all P>0.05).ConclusionsOur findings suggest that, among Brazilian adults living in moderate social vulnerability and classified within socioeconomic status B, C, and DE, mental health, BMI, waist-to-hip ratio, and quality-of-life indicators were similar across socioeconomic strata. However, these results should be interpreted as reflecting intra-group socioeconomic differences within a moderately vulnerable population and should not be generalized to individuals from the highest socioeconomic status.
<![CDATA[Expert explores fast-acting depression treatments, psilocybin trial pitfalls, and why stigma still limits buprenorphine access for opioid use disorder.]]>

Prediction of Clinically Significant Depressive Symptoms at 2-Year Follow-Up in Older Adults: Machine Learning Study Using the English Longitudinal Study of Ageing

Background: Depression in older adults is often underdiagnosed due to atypical symptom presentation and generational stigma, leading to delayed intervention. Early identification of individuals at risk of developing elevated depressive symptoms is therefore critical, but traditional approaches show limited predictive accuracy. To date, no study has applied machine learning (ML) models to predict clinically significant depressive symptoms at 2-year follow-up in older adults in the United Kingdom using data from the English Longitudinal Study of Ageing (ELSA). Moreover, the impact of encoding strategies for categorical health care variables has not been examined. Objective: This study aimed to develop and evaluate ML models to predict the clinically significant depressive symptoms at 2-year follow-up in older adults using ELSA data. We further compared ordinal and one-hot encoding strategies across different ML architectures and identified key predictors of depressive symptoms at follow-up. Methods: Data were drawn from 4 consecutive waves of ELSA, including participants aged ≥50 years without significant depressive symptoms at the baseline wave (waves 6‐9). Clinically significant depressive symptoms were defined as 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) scores of ≥4 at the subsequent wave (waves 7‐10). Over 120 features spanning sociodemographic, psychological, and health-related domains were analyzed. Eight ML models were applied, including tree-based ensembles, deep learning architectures for tabular data, distance-based methods, probabilistic methods, and linear methods. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC) and -score. Model interpretability was examined using Shapley additive explanations (SHAP). Sensitivity analyses assessed the robustness of results across alternative CES-D 8 thresholds (≥3, ≥4, and ≥5) and encoding strategies. Results: Across waves, the best-performing models achieved mean AUROC scores of 0.72‐0.73, with a peak of 0.75 in the highest-performing wave. Ordinal encoding consistently outperformed one-hot encoding across all ML models, yielding improvements in AUROCs and -scores, with the greatest increase in tree-based methods. SHAP consistently identified loneliness, sleep disturbances, and low social engagement as strong predictors of elevated depressive symptoms at follow-up. Sensitivity analyses across CES-D 8 thresholds demonstrated robust feature importance, with AUROCs ranging from 0.67 to 0.82. Traditional ML models (random forest, extreme gradient boosting, and support vector machines) generally achieved higher performance than the deep learning models for this task. Conclusions: Our findings demonstrate the feasibility of predicting clinically significant depressive symptoms at 2-year follow-up in UK older adults, with moderate accuracy. Ordinal encoding demonstrates superior performance for health care datasets with inherently ordered categorical features. The identification of consistent risk factors highlights opportunities for developing targeted clinical screening tools and preventive interventions. This study provides new evidence on depressive symptom prediction in the UK context, leveraging longitudinal data from ELSA, and contributes to advancing digital mental health research for aging populations.
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EFE-8c4, a polyamine from Elaeagnus multiflora, protects neuronal cells by regulating oxidative stress and apoptotic pathways

Neurological disorders, including depression, cognitive impairment, and neurodegenerative diseases, are closely associated with oxidative stress, apoptotic neuronal loss, and impaired neuronal differentiation. Polyamine derivatives from natural products have emerged as potential neuroprotective agents, although their mechanisms remain incompletely understood. In this study, three polyamine compounds isolated from Elaeagnus multiflora fruit were evaluated in SH-SY5Y cell models of oxidative and glucocorticoid-induced stress. Among these, EFE-8c4 exhibited the most pronounced neuroprotective activity, significantly restoring cell viability under corticosterone-induced stress and attenuating oxidative damage induced by hydrogen peroxide. Mechanistically, EFE-8c4 modulated apoptotic signaling by increasing Bcl-2 expression while suppressing Bax, caspase-8, and p53 activation, thereby restoring the balance between pro- and anti-apoptotic pathways. In addition, EFE-8c4 reduced intracellular reactive oxygen species accumulation and enhanced the expression of PCNA and βIII-tubulin, indicating improved cell survival capacity and neuronal phenotype maintenance. Furthermore, EFE-8c4 partially reduced apoptotic cell populations under corticosterone exposure. Collectively, these findings demonstrate that EFE-8c4 exerts multi-target neuroprotective effects through coordinated regulation of apoptosis, oxidative stress, and neuronal differentiation-related pathways, highlighting its potential as a candidate for the treatment of oxidative stress-associated neurological disorders.

Burned aggression: the relationship between burnout and aggressive behaviour among young adults in Czechia

IntroductionDespite stress being a critical component of burnout, few studies have investigated the relationship between burnout and aggressive behaviour. Therefore, the current study aims to verify whether states of exhaustion are associated with aggression.MethodsStructural equation models were constructed using data from a representative sample of 1027 young adults (Mage = 24.53), almost half of whom were men (n = 507). The models revealed the relationships between burnout, aggressive behaviour, emotion regulation strategies, risky alcohol consumption, stress, and adverse childhood experiences. ResultsAlthough there were minor differences in the pathways between men and women, both models showed a good fit for the data. Furthermore, among both men and women, the positive relationship between burnout and aggressive behaviour was mediated by maladaptive coping strategies and risky alcohol consumption. Interestingly, reliance on maladaptive emotion regulation strategies was also associated with increased depressive symptoms among women but not among men.ConclusionThe findings of this study reveal that aggressive behaviour is another negative consequence of burnout among young adults and highlight the importance of skills applied in responses to chronic stress. The implications of these findings and further results are discussed in relation to the existing literature.

The relationship between mobile phone addiction and depression, anxiety among Chinese college students: the mediating role of friendship quality and the moderating effect of preference for solitude

BackgroundThe university stage represents a critical period for the development of individual mental health. Mobile phone addiction is closely linked to depression and anxiety among college students, and both friendship quality and preference for solitude are tightly associated with college students’ mobile phone addiction and emotional health. Therefore, this study aimed to investigate the relationships and internal mechanisms among mobile phone addiction, friendship quality, preference for solitude, depression and anxiety in college students.MethodsA total of 1083 Chinese college students (58.2% female; mean age = 19.87 ± 1.692 years) were included as participants. Data were collected using the Mobile Phone Addiction Index, Friendship Quality Questionnaire, Preference for Solitude Questionnaire, and Depression Anxiety Stress Scale. Data processing and analyses were conducted using SPSS 26.0 and the PROCESS macro.Results(1) Mobile phone addiction was significantly negatively correlated with friendship quality, and significantly positively correlated with both depression and anxiety; friendship quality was significantly negatively correlated with depression and anxiety; preference for solitude was significantly positively correlated with depression and anxiety. (2) Mobile phone addiction not only directly and positively predicted depression and anxiety among college students, but also predicted depression and anxiety through the mediating role of friendship quality. (3) The direct effect of mobile phone addiction on depression and the mediating effect of friendship quality in the relationships between mobile phone addiction and depression/anxiety were both moderated by preference for solitude, whereas the moderating effect of preference for solitude on the association between mobile phone addiction and anxiety was not significant.ConclusionFriendship quality serves as an important mediating pathway between mobile phone addiction and depressive and anxiety symptoms among Chinese college students. Preference for solitude may amplify the associations of mobile phone addiction with poorer friendship quality and elevated depressive symptoms.