New co-drugs of O-demethylvenlafaxine and NSAIDs exert antidepressant effects by alleviating inflammation, oxidative stress, and increasing neurotransmitter.

Approximately 450,000 Veterans are living with Alzheimer disease and related dementias (ADRD), and the high prevalence of ADRD represents a major public health challenge for the Veterans Health Administration. While advancing age and genetic predisposition are well-established ADRD risk factors, growing evidence suggests that additional modifiable factors may also play an important role. This study leveraged data from the VA Million Veteran Program (MVP) to (1) estimate 10-year incidence of ADRD and (2) evaluate associations between a broad range of individual-level risk and resilience factors and incident ADRD in a large, nationally representative sample of Veterans. This retrospective cohort study included Veterans aged ≥65 years at MVP enrollment who completed the MVP Baseline Survey and had VA electronic health record (EHR) data available. Individual-level variables including sociodemographic factors, military-specific characteristics, military environmental exposures (MEEs), health conditions, and health behaviors were characterized using MVP Baseline Survey data and supplemented with EHR data as available. The primary outcome was ADRD, which was determined using a validated algorithm based on International Classification of Diseases diagnosis codes extracted from the EHR. Associations between each risk/resilience factor and incident ADRD were examined using separate Cox regression models adjusted for age, sex, and education. The sample included 245,949 Veterans (age: mean 73.16, SD 6.84 years; 2.59% female). Approximately 4.56% (n = 11,216) of the sample developed ADRD over 10 years. History of traumatic brain injury (TBI; hazard ratio [HR] 2.96, 95% CI 2.76-3.17), depression (HR 2.93, 95% CI 2.82-3.04), and alcohol use disorder (AUD; HR 2.35, 95% CI 2.19-2.53) were the health factors most strongly associated with ADRD. ADRD risk was also elevated among Veterans with a history of exposure to Agent Orange (HR 1.09, 95% CI 1.03-1.14), chemical/biological warfare agents (HR 1.31, 95% CI 1.23-1.39), and pyridostigmine bromide tablets (HR 1.67, 95% CI 1.44-1.93). Findings identified TBI, depression, AUD, and MEEs as key variables associated with ADRD in Veterans. These factors may represent important targets for prevention and intervention efforts aimed at improving the long-term health of aging Veterans. Additional work is needed to clarify the mechanisms through which these factors influence ADRD risk and to establish whether observed associations are causal.

Spatiotemporal co-occurrence and shared exposure profiles of adolescent depressive disorders and asthma worldwide and in China (GBD 2021, 1990-2021): an ecological study with bidirectional two-sample Mendelian randomization.

Decomposing the Association Between Neighborhood Homicide Rates and Stress-Related Health Outcomes Among Black Men in Chicago.

Moderating Effect of Participation in Organized College Sports on Mental Health and Frequency of Cannabis Use in a National Cohort.

Transitions in comorbidity patterns of depression and internet gaming disorder among adolescents: A random intercept latent transition analysis.

Little is known about 'touch hunger' (longing for physical contact) during the COVID-19 pandemic, particularly for people with pre-existing mental health disorders. We aimed to 1) explore whether touch hunger differs between people with and without depressive, anxiety, or obsessive-compulsive disorders during the COVID-19 pandemic, 2) study the development of touch hunger in relation to loneliness, and 3) examine its predictors during lockdown. Data were aggregated from three Dutch ongoing prospective cohorts with similar methodology for data collection. We included participants with pre-pandemic data gathered during 2006-2016, and who completed up to 9 online questionnaires between October 2020 and February 2022. Touch hunger trajectories were analyzed using linear mixed models. Sociodemographics, personality traits, (chronicity of) mental health disorders, and COVID-19-related factors were analyzed as predictors of touch hunger using multivariate linear regression analyses. We included 1061 participants with (n=811) and without (n=250) mental health disorders. In all chronicity groups, touch hunger increased during lockdown and decreased after lockdown. Extraversion (β=0.256, P<0.001), social distancing due to COVID-19 anxiety (β=0.122, P=0.001), and death of a close contact from COVID-19 (β=0.073, P=0.02) predicted higher touch hunger, while living with a partner (β=-0.109, P=0.004) or with a partner and children (β=-0.147, P<0.001) were protective factors for touch hunger. Remarkably, pre-pandemic psychiatric diagnosis did not predict touch hunger during lockdown. Touch hunger rose during the lockdown and was widespread regardless of mental health conditions, indicating a fundamental human need for physical contact, especially among extroverts.

Personality moderates the predictive value of serum serotonin for antidepressant remission in depressive disorders.

Pharmacogenomic testing may optimize antidepressant treatment in depression. Its effects on cognition and across age groups remain unclear. A total of 843 patients with depressive disorder were stratified by age (adolescent, young adult, middle-aged, elderly) and assigned to pharmacogenomic-guided or treatment-as-usual groups. Guided treatment was based on pharmacogenomic results. Primary outcomes were changes in Montreal Cognitive Assessment (MoCA), remission (HDRS<8), and response (≥50% HDRS reduction) at weeks 4, 8, and 12. MoCA improvement inversely correlated with age (week 8: r=-0.078, P=0.036; week 12: r=-0.076, P=0.041). Pharmacogenomic guidance was associated with greater cognitive gains in younger participants, with sustained improvement in adolescents (all P≤0.036), improvement in young adults at weeks 8 and 12 (both P≤0.013), and transient benefit in middle-aged patients at week8 (P=0.048). No cognitive benefit was observed in the elderly. Multi-way ANOVA for depressive symptoms (HDRS) revealed a Group×Time interaction (P<0.001), and for cognitive function (MoCA) showed both a Group×Time interaction (P=0.011) and an Age×Time interaction (P=0.024), consistent with age-dependent recovery trajectories. Pharmacogenomic guidance was associated with increased remission and response rates from week 8 through week 12 across all ages. single blinded; single-center design. Pharmacogenomic-guided treatment consistently improves depressive symptom remission but shows age-dependent cognitive effects: sustained in youth, transient in middle age, absent in elderly. Age is a key modifier of cognitive benefit, supporting prioritized use in younger patients, while elderly individuals may require integrated interventions beyond pharmacogenomics.

Recent advances in high-throughput technologies have led to an increased generation of biological data across genomics, transcriptomics, proteomics, epigenomics, and metabolomics. However, a major challenge remains: effectively integrating these multi-omics datasets to allow a more holistic understanding of the complex, interconnected mechanisms underlying human diseases. Neurodevelopmental, neurodegenerative, and psychiatric disorders are particularly multifactorial and heterogeneous, making them candidates for multi-omics approaches. In this context, this systematic review assesses the current state of multi-omics integration in neurological research. Records retrieved from five major databases were processed, and 156 studies were included for further analysis. The most frequently studied conditions were Alzheimer's Disease, Depressive Disorder and Parkinson's Disease, with epigenomics-transcriptomics and metagenomics-metabolomics emerging as the most common omics pairings. The field remains dominated by studies integrating pairs of omics layers. Only a limited number of computational tools are currently being applied to the integration of more than two omics layers, highlighting a gap in comprehensive multi-omics modeling. Despite progress, key challenges persist, including data accessibility and the need for standardized frameworks to allow cross-study comparisons. Moreover, most computational findings lack experimental validation in wet-laboratory settings. Future research should address these challenges, develop scalable algorithms for integrating multi-omics data, and leverage large, open-access datasets. Integrating computational predictions with experimental validation could help researchers prioritize high-confidence biomarkers relevant to clinical applications. Collaborative efforts among bioinformaticians, clinicians, and experimentalists will be essential to translating these advances into clinically actionable solutions.

Chronic psychological stress induces pulmonary dysfunction through alveolar macrophage-mediated activation of apoptotic signaling pathways.

Depression is a frequent comorbidity in dementia; however, diagnosis is complicated by overlapping cognitive and behavioural symptoms. The Geriatric Depression Scale (GDS) is a widely used screening tool to probe for depression, comprising 30 items in its full version (GDS-30) but also existing as a range of shorter versions (GDS-15, GDS-10, GDS-8, GDS-4). All versions contain items that may be confounded in dementia patients such as probes for cognitive symptoms, apathy, and negative feelings about the future. This study aimed to develop and validate a 10-item version (GDSD) optimised for diagnosing depression in dementia by removing these confounds. Data were retrospectively analysed in participants with Alzheimer's disease (AD, n=29), frontotemporal dementia (FTLD, n=30), or a depressive disorder (n=23) who had completed the GDS-30 and undergone psychiatric assessment and application of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria. Diagnostic accuracy of the GDS-D was compared to all previous GDS versions using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The GDS-D had an accuracy of 92-97% in diagnosing depression in a memory clinic setting and in dementia (AD and FTLD), which was superior to the GDS-30 and all briefer versions. The GDS-D enhances depression screening in a memory clinic setting by excluding the confounding items of other GDS versions. In addition, it performs better at diagnosing depression in a dementia cohort. Future studies should validate its utility in larger, diverse dementia populations.

Auricular stimulation therapy: An evidence-based practice strategy for depression.

Major depressive disorder and bipolar disorder are affective disorders that carry substantial disease burdens, yet the structural brain alterations due to recent mood episodes remain unclear. To identify acute effects on brain structure, we compared cortical thickness in adults with and without a mood episode in the past year. Participants were 30 adults who met lifetime DSM-5 criteria for MDD (n=21) or BD (n=9), divided into a Past Year Mood Episode (PYME) group (n=18), and no-PYME group (n=12). Participants completed the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS) and the semi-structural Longitudinal Interval Follow-up Evaluation (LIFE) interview over the year preceding their structural MRI. The PYME group exhibited greater cortical thickness than the no-PYME group in the left medial orbitofrontal cortex, bilateral V1 primary visual cortex (more extensive in the left hemisphere than the right), left V3 and right V2 visual cortices, and the bilateral hippocampus and left presubiculum. Recent mood episodes are linked to increased cortical thickness, possibly reflecting acute compensatory inflammatory responses. Cortical thickness thus shows promise as a transdiagnostic biomarker of recent mood episodes, aiding interpretation of studies that include individuals who are currently euthymic but recently symptomatic.

Neurophysiology of pleasant touch: From peripheral mechanisms to clinical implications of caressing.

Effect of diary intervention on sleep quality and risk of stress disorders among critically ill children in pediatric intensive care units and on their parents' anxiety level: A randomized controlled trial.

This study explores processes of change for individuals who responded to low-intensity Cognitive Behavioural Therapy (CBT) for depression, Generalised Anxiety Disorder (GAD), or panic disorder. Routinely collected data from NHS Talking Therapies for Anxiety and Depression (TTad) services (N = 11, 396, 69.2% female) were analysed using network analyses. Nine Gaussian graphical models (GGMs) were conducted: for each disorder, across three time phases (assessment to start-of-treatment; start to mid-point of treatment; mid-point to end-of-treatment). Each GGM included 19 nodes, based on PHQ-9, GAD-7,and NHS TTad phobia scores, using residuals as indices of change for each node. Networks of symptom change were largely similar. Estimated network matrix similarity ranged between r = .74 and r = .91 across disorders, with depression and GAD networks more similar to each other than to panic disorder. Networks varied over time within the same disorder, more so for panic disorder (r = .61-.63) than GAD (r = .86-.90) or depression (r = .87-.93). There were close links between changes in worry-related items and feeling nervous or anxious, and between depressed mood and anhedonia across all networks, as well as links between sleep disturbance, appetite, trouble relaxing and irritability. Findings suggest shared patterns of co-change across anxiety and depression. There is a potential indication that therapy may work by leveraging existing natural change mechanisms rather than by creating entirely new patterns of symptom interaction. Networks also show associations between symptom changes specific to certain disorders at certain points in therapy.

Propolis, a natural wax-like resinous substance present in bee hives, has been extensively used in dietary supplements and as folk medicine for the treatment of several diseases, including neurological disorders. Propolis has been used as a traditional medicine for the treatment of depression and other neurological disorders. This review aims to investigate the clinical studies and various therapeutic potentials associated with propolis, direct the future scope of research, and discuss possible clinical implications. A total of 143 papers were selected using a database comprising Google Scholar, Scopus, PubMed, and Web of Science. Diverse keywords, such as propolis, bee, phytochemistry, pharmacology, and clinical study, were used to search the content. This review highlights the diverse biological activities of propolis, as evidenced by preclinical and clinical studies. In experimental models, propolis extract exhibited antidepressant-like and vasculoprotective effects, primarily through its anti-inflammatory and antioxidant potential. These benefits were associated with the suppression of pro-inflammatory cytokines, chemokines, and angiogenic factors. Propolis extract was found to delay the progression of atherosclerosis by improving lipid metabolism and modulating apoptosis. Furthermore, both in vitro and in vivo investigations suggest that propolis may protect vascular endothelial function due to its antiproliferative activity. Notably, anticancer potential was observed against the ovarian cancer cell line M12.C3.F6. Clinical studies also provided encouraging findings. In patients with type 2 diabetes mellitus, propolis extract has been shown to improve wound healing parameters in diabetic foot ulcers. Another trial reported promising outcomes with propolis extract formulated as niosomal oromucosal-adhesive films for recurrent aphthous ulcers. Overall, these results underline the multifaceted therapeutic promise of propolis across neurological, vascular, oncological, and wound-healing domains. This review summarizes clinical and experimental evidence on the therapeutic potential of propolis. It highlights its immunomodulatory, antioxidant, antimicrobial, antifungal, anticancer (skin, oral, lung, breast, cervical), antidepressant, anxiolytic, cardiovascular, chemopreventive, and anti-angiogenic properties. Several studies, including clinical trials, suggest its potential role in combating COVID-19 and other health conditions. Overall, findings indicate that propolis possesses significant medicinal promise and may serve as a lead candidate for developing novel therapeutic agents.

Cannabis use is increasingly prevalent among U.S. veterans, with high rates of both recreational and problematic use. Veterans often use cannabis to manage symptoms associated with mental health problems such as depression and posttraumatic stress disorder (PTSD). Prior work has noted mixed results on the longitudinal associations between cannabis use and depression. Studying these associations at the daily level can lead to improved clarity. The present study examined the daily associations between cannabis use and depression in veterans using dynamic structural equation modeling (DSEM). We also explored these associations for those veterans who screened positive for posttraumatic stress disorder (PTSD) compared to those who did not. All participants were recruited using advertisements from BuildClinical, an NIH approved recruitment vendor. The sample consisted of 74 veterans who provided daily data for 87 consecutive days. Cannabis was assessed asking how many hours each individual spent high each day, depressed mood was assessed using a sliding scale from not depressed to very depressed each day, and PTSD was assessed using the PTSD checklist. Among the full veteran sample results revealed a bidirectional, negative, association. Specifically, on days when veterans reported greater depression, they reported fewer hours "high" the next day. Conversely, on days when veterans reported a greater number of hours high, they reported less depression the next day. Among veterans screening positive for PTSD, on days when they reported more depression, they reported fewer hours high the next day (no association was noted for cannabis use predicting depression). However, for those who did not screen positive for PTSD, on days when veterans reported greater number of hours high, they reported less depression the next day. These results highlight the need for further research on the effect of individual differences in cannabis use patterns among veterans with PTSD on health outcomes. Clinically, these results highlight the importance of targeting the pros and cons of cannabis use for depression symptom relief. Future research should incorporate daily objective measures of cannabis use to refine treatment strategies for veterans managing PTSD or depressive related distress.

Depression is a common mental disorder. Patients with treatment-resistant depression (TRD) often experience sleep disorders (SD), which interact with each other and aggravate the deterioration of the disease. In this study, we analyzed the effect of paroxetine combined with low-dose quetiapine on patients with treatment-resistant depression complicated by sleep disorders. We divided treatment-resistant depression + sleep disorders 120 patients into a control group treated with paroxetine and a research group treated with paroxetine + low-dose-quetiapine. Hamilton Depression Scale (HAMD-17), Self-rating Anxiety and Depression Scale (SAS/SDS), Pittsburgh Sleep Quality Index (PSQI) and serum indexes (cortisol, epinephrine, thyroid hormone, etc.) were used to analyze the data. In terms of clinical efficacy, the research group demonstrated superior efficacy. Besides, the research group showed lower self-rating anxiety/depression scale scores than the control group after treatment (P<0.05). In terms of sleep quality, the Pittsburgh Sleep Quality Index of the research group also decreased more significantly compared with the control group (P<0.05). Moreover, better stress injury alleviation and endocrine function improvement were determined in the research group (P<0.05). The two groups were not statistically different in treatment compliance and adverse reactions (P>0.05). Paroxetine combined with a low dose of quetiapine is a clinically effective approach for treatment-resistant depression with sleep disorders and is recommended for clinical use.