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Depression

Depression: explore 29 source-linked works published from 2026 to 2026, with original documents and citations.

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Sources: pubmed. Collection updated 2026-09-15. Counts describe this index, not the complete source archives.

PubMed2026

Effects of Esketamine on Postoperative Hospital Anxiety and Depression Scale Scores in Patients Undergoing Laparoscopic Radical Resection for Colorectal Cancer.

OBJECTIVE: To investigate the effects of intravenous esketamine on postoperative Hospital Anxiety and Depression Scale (HADS) scores in patients undergoing laparoscopic radical resection for colorectal cancer. METHODS: In this prospective, randomized, placebo-controlled study, adult patients for elective laparoscopic radical resection were randomly assigned (1:1) to a control group (group C) or an esketamine group (group PE). Group C received conventional general anesthesia and patient-controlled intravenous analgesia (PCIA). In group PE, esketamine 0.5 mg/kg was injected during induction of anesthesia, with esketamine 1 mg/kg added to PCIA. Primary outcome was HADS score on postoperative day 1. Secondary outcomes included HADS scores on postoperative days 3 and 7, sleep quality scores, postoperative level of consciousness, complication rate, length of hospital stay, 24 h inflammatory factors, and satisfaction scores. RESULTS: Group PE showed significantly lower HADS-A and HADS-D scores on postoperative days 1 and 3 , reduced 24 h interleukin-6 (IL-6) leveland higher patient satisfaction compared with group C (all p < 0.05). CONCLUSIONS: Esketamine given during induction and in PCIA reduced early-stage postoperative HADS scores and improved patient satisfaction in colorectal cancer patients.

Humans↗

PubMed2026

Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.

BACKGROUND: With the increasing prevalence of depression, there is an urgent clinical need for early screening in depression. The retina offers a promising window for early screening in depression due to its rapid, non-invasive, objective, eye-brain correlated characteristics, but previous research has yielded conflicting alterations in retinal microstructure in depression. METHODS: We screened retinal optical coherence tomography and brain magnetic resonance imaging data in the UK Biobank to enroll 23,225 participants for retinal study of depression occurrence, and 1475 participants for the eye-brain association study. We also used genetic data (ID: ebi-a-GCST90014267 and ukb-d-20,448) from the Integrative Epidemiology Unit Open Genome-Wide Association Study for Mendelian randomization analysis. We used Cox regression to assess the association between retinal microstructure and depression risk, Mendelian randomization to infer causality, and mediation analysis to explore retina-brain pathway association. RESULTS: The Cox regression analysis showed that retinal ganglion cell-inner plexiform layer (GCIPL) thickness remained a significant predictor of depression. The Mendelian randomization analysis indicated a positive statistical association between GCIPL thickness and depression. Moreover, there was a significant positive correlation (all p < 0.001) between the volume of specific depression-related brain regions and the GCIPL thickness. Adjusting for age, sex, and head size, the mediation analysis provided preliminary evidence for a potential anatomical pathway linking retinal GCIPL thickness to depression-related brain regions through primary visual cortex and secondary visual cortex volumes. CONCLUSION: Thickened retinal GCIPL is a potential early phenotype of depression and has a potential association pathway with depression-related brain regions using a radiogenomics approach.

Humans↗

PubMed2026

Patient-reported outcome measures for depression or anxiety symptoms in patients with cardiovascular disease: A COSMIN systematic review.

BACKGROUND: Depression and anxiety are common in patients with cardiovascular disease (CVD), but the measurement quality of patient-reported outcome measures (PROMs) used in this population remains unclear. This review aimed to evaluate the methodological quality, measurement properties, and certainty of evidence for depression and anxiety PROMs in adults with CVD and to inform instrument selection. METHODS: Following COSMIN and PRISMA guidance, four databases were searched from inception to February 2026. Studies assessing measurement properties of PROMs in adults with CVD were included. Methodological quality was evaluated using the COSMIN Risk of Bias checklist, and certainty of evidence was graded using an adapted GRADE approach. RESULTS: Sixty-six studies assessing 38 PROMs were included, comprising 29 generic and 9 CVD-specific instruments. Six PROMs met COSMIN Category A criteria: Cardiac Depression Scale-Short Form, Patient Health Questionnaire-9, Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Generalized Anxiety Disorder-7, and Major Depression Inventory. Four instruments were classified as Category C because of insufficient structural validity. Content-validity evidence was largely indeterminate or of limited certainty. Only 24 studies used confirmatory factor analysis or Rasch analysis, and no study assessed measurement error or responsiveness. Cross-cultural validity evidence was scarce. CONCLUSIONS: Six PROMs met Category A criteria, but selection should remain purpose- and context-specific. Particular attention should be given to somatic symptom overlap and intended clinical use. Further validation should prioritize content validity, measurement invariance, responsiveness, measurement error, and clinimetric performance.

Humans↗

PubMed2026

Fyn signaling in the medial prefrontal cortex regulates resistance to stress-induced object recognition impairments in male rats.

Genome-wide association studies on patients with depression have identified FYN and FYB, an FYN-binding protein, as being linked to depression. We have reported that experimental manipulations in gene expression in the medial prefrontal cortex (mPFC) alter stress-induced object recognition impairments in animals. Therefore, we examined the impact of alterations in FYN and FYB expression in the mPFC of adult male rats on resistance to stress-induced impairments in object recognition. Animals with virus-mediated knockdown or overexpression of Fyn in the mPFC were subjected to either a brief 20-min restraint with 20 intermittent tail shocks, which does not induce object recognition impairment, or a prolonged 60-min restraint with 60 intermittent tail shocks, which does. In an object recognition task, control rats maintained intact object recognition following a brief stress, whereas rats with Fyn knockdown or overexpression in the mPFC showed impaired object recognition. Prolonged stress impaired object recognition in both control rats and rats with Fyn knockdown or overexpression. Additionally, rats with Fyn knockdown in the mPFC exhibited fewer c-Fos-positive cells in the mPFC in response to brief stress, accompanied by a trend toward increased c-Fos in the amygdala compared with control rats. Fyn knockdown also reduced Fyb expression in the mPFC. Furthermore, Fyb knockdown in the mPFC impaired object recognition following brief stress, suggesting that the observed effects are consistent with involvement of a coupled Fyn-Fyb signaling axis rather than Fyn alone. These findings suggest that altered Fyn-related signaling in the mPFC may underlie the resistance to stress-induced object recognition impairments.

Animals↗

PubMed2026

Effects of acute inflammatory challenge on anhedonia and social reward processing: A randomized controlled trial of endotoxin.

Anhedonia is a core feature of depression that reflects reward system dysfunction. Acute inflammatory challenge has been shown to induce transient anhedonia and reward processing deficits, but its effects on distinct components of social reward processes remain poorly understood. This randomized, double-blind, placebo-controlled study evaluated anhedonia and social reward responsivity following acute inflammatory challenge. Low-dose endotoxin (0.8 ng/kg body weight; n = 18) or placebo (same volume of 0.9% saline; n = 22) was administered to female adults (ages 25-44). Anhedonia (Snaith-Hamilton Pleasure Questionnaire) and blood samples for cytokine assessment were collected pre-infusion and 2 and 4 h post-infusion. Social reward motivation (wanting to engage in a social task) was assessed at a baseline eligibility visit and 2 h post-infusion. Sensitivity to positive social cues (attentional bias toward and recognition of happy faces) was assessed pre-infusion and 2 h post-infusion. Results showed that endotoxin increased anhedonic symptoms (p = .005) and decreased social motivation by 2 h post-infusion (p = .001); within the endotoxin condition, changes in both outcomes were associated with increases in TNF-α (p's < .04). A significant condition-by-time interaction for happy-face recognition (p = .011) was driven by increased accuracy in the placebo (p = .04) but not endotoxin (p = .43) condition. Endotoxin administration did not affect attentional bias toward happy faces. Findings suggest that acute inflammatory challenge induces anhedonia and reduces social motivation, with more limited effects on sensitivity to positive social cues, highlighting specific reward-related pathways through which immune activation may contribute to inflammation-associated depression. Future work could examine whether immune-related changes in social motivation contribute to motivational deficits in depression.

Humans↗

PubMed2026

Exploring the dose-response relationship between prenatal exercise and postpartum depression: A systematic review and meta-analysis of randomized controlled trials.

IMPORTANCE: Postpartum depression (PPD) is a hidden and widespread global public health crisis affecting millions of mothers and infants annually. Prenatal exercise is a potentially accessible nonpharmacological strategy for PPD prevention, but its optimal dose remains uncertain. OBJECTIVE: To explore the dose-response relationship between prenatal exercise and the incidence of PPD through meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library using MeSH terms and keywords related to "pregnant women," "prenatal exercise," and "postpartum depression," up to June 23, 2025. STUDY SELECTION: RCTs included examined prenatal exercise interventions in pregnant women without a history of depression, with PPD incidence reported using validated depression scales (such as EPDS, CES-D). Non-RCT studies, duplicate publications, and studies with insufficient data were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data according to the PRISMA guidelines. A random-effects model was used to pool odds ratios (OR) and their 95% confidence intervals (CI). Linear and nonlinear dose-response models were employed to analyze and evaluate the relationship between exercise dose (measured in METs-min/week) and the incidence of PPD. MAIN OUTCOME(S) AND MEASURE(S): The primary outcome is the incidence of PPD, analyzing its relationship with prenatal exercise dose. RESULTS: Eight RCTs involving 2231 pregnant women were included. The pooled analysis showed that prenatal exercise was associated with a potential reduction in PPD incidence, although the overall effect did not reach statistical significance (OR=0.58, 95% CI [0.33, 1.02]). In dose-stratified analysis, exercise doses ≥500 METs-min/week were associated with significantly lower PPD incidence (OR=0.44, 95% CI [0.24, 0.78]). Subgroup analyses suggested trends toward greater benefits among women aged ≥30 years and those initiating exercise between 14 and 28 weeks of gestation; however, subgroup differences did not reach statistical significance. The linear dose-response trend did not reach statistical significance (p = 0.0533), and neither the overall spline association (p = 0.1704) nor the test for nonlinearity (p = 0.6361) was statistically significant. CONCLUSIONS AND RELEVANCE: Prenatal exercise may be associated with a lower risk of PPD, but the overall pooled effect did not reach statistical significance. Findings concerning ≥500 METs-min/week and the apparent flattening of the dose-response curve should be considered exploratory and require confirmation in larger trials.

Humans↗

PubMed2026

Elastic tape as an add-on strategy to potentiate pulmonary rehabilitation outcomes in nonobese males with moderate-to-very severe COPD: A randomised clinical trial.

BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) improves exercise capacity but has limited effects on ventilatory constraints in severe COPD. Application of elastic tape (ET) is a potential adjunctive strategy that improves ventilatory efficiency, but its effects during PR remain un lear. This study investigated whether ET potentiates PR benefits on exercise capacity, health status, psychological symptoms, and health-related quality of life (HRQoL) in individuals with COPD. METHODS: Forty-two nonobese men with moderate-to-very severe COPD were randomised to ET or Sham groups during an 8-week PR programme. The primary outcome was endurance shuttle walk test (ESWT) time; secondary outcomes included COPD Assessment Test (CAT), Chronic Respiratory Questionnaire (CRQ), and Hospital Anxiety and Depression Scale (HADS). RESULTS: ESWT improved by +329s in the ET group, exceeding the MCID. Greater CAT improvements (p = 0.02), and a higher proportion achieving minimal clinically important difference (MCID) (48% vs. 29%; p = 0.02) were observed in the ET group. Only ET group achieved MCIDs for depression (p = 0.003) and anxiety (p = 0.02). HRQoL improved similarly in both groups. The only outcome with a significant time × group interaction was HADS-D (p = 0.001), improved by ET. Only This study was performed in accordance with the Declaration of Helsinki. This human study was approved by Ethics Committee for Analysis of Research Projects (CAPPesq) of School of Medicine of the University of São Paulo - Hospital das Clínicas (approval 55 617 321.20000.0068). All adult participants provided written informed consent to participate in this study. Clinical Trial Registration number NCT05939999 (https://clinicaltrials.gov), registered on October 26th, 2025.ET group presented moderate-to-large effect sizes for ESWT (d = 0.89), HADS-A (d = 0.51) and HADS-D (d = 1.02). CONCLUSIONS: ET potentiates PR benefits on exercise capacity, health status, and psychological symptoms in individuals with moderate-to-very severe COPD.

Humans↗

PubMed2026

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

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PubMed2026

Short-term aerobic exercise as an adjunct treatment for depression in acute geriatric psychiatry: Results of a randomized controlled trial.

BACKGROUND: This randomized controlled trial examined whether short-term aerobic exercise provided additional clinical benefit over an active control in older inpatients with depression in geriatric psychiatry. METHODS: 100 patients (mean age 76 years) were randomized to 2-week supervised aerobic ergometer training (intervention group, IG) or a flexibility program (control group, CG), both delivered in addition to treatment as usual (TAU). Adherence, training exposure and adverse events were recorded to assess feasibility. The primary outcome was clinical improvement measured with the Clinical Global Impression of Change (CGI). Secondary outcomes included depressive symptom severity assessed by the Beck Depression Inventory-II (BDI-II) and clinician-rated Hamilton Rating Scale for Depression (HAMD), physical activity, 6-min walk test (6MWT) performance, and fluoxetine-equivalent antidepressant dose (FLX). RESULTS: Thirty-nine participants attended at least 80% of sessions, with lower adherence in the IG. Weekly training duration differed between groups (74.0 ± 31.9 vs. 95.0 ± 25.3 min/week, p = .003). CGI did not differ between groups (IG: MD -0.31, 95% CI -0.67 to 0.05; p = .069). Depressive symptom severity decreased over time in both groups (p < .001), without significant between-group differences for HAMD (MD -0.22, 95% CI -2.55 to 2.12) or BDI-II (MD -0.62, 95% CI -3.68 to 2.45). 6MWT and FLX increased over time (both p < .001), without group differences (6MWT: MD -1.08 m, 95% CI -20.04 to 17.89; FLX: MD 5.69 mg/day, 95% CI -2.40 to 13.77). CONCLUSION: Short-term aerobic exercise was deliverable, but showed no additional clinical benefit over low-intensity flexibility during TAU. Further research should determine dose, duration and adherence for clinically relevant effects.

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

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals↗

PubMed2026

Effectiveness and implementation of task-sharing cognitive-behavioral interventions for perinatal mental health: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cognitive-behavioral interventions (CBIs) delivered by nonspecialist providers (NSPs) on perinatal depressive (PND) and anxiety symptoms, and to narratively synthesize their implementation processes and reported implementation outcomes, including acceptability, feasibility, fidelity, cost, and sustainability. METHODS: We systematically searched eight databases from inception to April 8, 2025. Eligible studies were randomised controlled trials (RCTs) assessing CBIs delivered by NSPs for PND and/or anxiety. Two reviewers independently screened, extracted, and assessed trials. Meta-analyses employed random-effects models, with subgroup, sensitivity, meta-regression, and publication bias analyses conducted in Stata 18.0. Implementation processes and outcomes were reported as frequencies or percentages across trials. RESULTS: A total of 47 trials (11, 357 participants) were included in the systematic review, of which 37 trials (8,709 participants) were included for meta-analyses. CBIs were conducted in 12 countries. Nurses and midwives delivered 45% of CBIs. CBIs were associated with reduced PND post-intervention compared with control conditions (standardized mean difference [SMD] -0.49, 95% CI -0.63 to -0.35; I² = 86.8%). Limited evidence from four trials suggested a small sustained effect at 12 months (SMD -0.14, 95% CI -0.27 to -0.02; I² = 26.4%). Reductions in anxiety symptoms were observed immediately post-intervention (SMD, -0.45, 95% CI -0.65 to -0.25; I²=81%), but evidence for longer-term effects was limited. Subgroup analyses confirmed consistent effects across diverse settings, populations, and intervention characteristics. Reporting of implementation processes (e.g., training, supervision, fidelity) was limited, with only 23.4% of trials assessing fidelity and 10.6% evaluating costs. CONCLUSIONS: NSP-delivered CBIs showed beneficial effects on PND and anxiety, with generally encouraging evidence for acceptability and feasibility. However, evidence for sustained effects beyond the immediate post-intervention period remains limited. Future studies should strengthen long-term follow-up and improve reporting of implementation processes and outcomes, particularly in rural and adolescent perinatal populations, to inform scalable and equitable task-sharing models.

Humans↗

PubMed2026

The effects of mindfulness-based cognitive therapy in the psychological and physical health of cancer patients: A systematic review and meta-analysis.

PURPOSE: No prior systematic review has specifically evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) in improving both psychological and physical outcomes among cancer populations. This study aims to assess MBCT's effects on cancer patients' mental and physical health. METHOD: Following PRISMA guidelines and with PROSPERO registration (CRD42023453581), we systematically searched PubMed, Cochrane CENTRAL, Embase, and Web of Science for randomized controlled trials (RCTs) were searched up to June 2026. Eligible trials enrolled adults (≥ 18 years) with any cancer type/stage, compared MBCT delivered per standard manual against non-MBCT controls, and reported at least one validated measure of distress, depression, or anxiety; secondary outcomes included fatigue, quality of life, and mindfulness skills. Two reviewers independently selected studies, extracted data, and assessed risk of bias using the Cochrane tool; random-effects meta-analyses were performed in Stata 16. RESULTS: 11 RCTs comprising 1122 participants (mean age 54.8 years; 91% female) were included. MBCT produced large, significant reductions in psychological distress (SMD = -0.81, 95% CI-1.27 to-0.40), depression (SMD = -0.95, 95% CI -1.40 to-0.49), and anxiety (SMD = -0.86, 95% CI -1.22 to-0.51). It also markedly decreased fatigue (SMD = -0.83, 95% CI-1.10 to-0.56), improved quality of life (SMD = 0.56, 95% CI 0.22-0.88), and enhanced mindfulness skills (SMD = 0.76, 95% CI 0.59-0.92). CONCLUSIONS: This meta-analysis is the first to exclusively synthesize RCT evidence of standardized MBCT in cancer care, demonstrating significant dual benefits for emotional and physical well-being while providing strong support for integrating MBCT into comprehensive oncology rehabilitation.

Humans↗

PubMed2026

Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial.

BACKGROUND: Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients. METHODS: This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (0.9% saline) 24 h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96 h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories. RESULTS: The trial randomized suicidal inpatients to ketamine (n = 73) or placebo (n = 83). Psychological pain decreased in both groups but was lower with ketamine during the first 96 h. Pointwise scores were lower with ketamine from 40 min to 96 h, largest at 40 min, 2 h, 4 h, and 24 h (all p < 0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified. CONCLUSIONS: Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96 h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.

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

Genetic evidence for a causal relationship between melatonin metabolism and depression.

To investigate the causal relevance of melatonin metabolism, which provides the biological basis for circulating melatonin levels, to specific depression symptom subtypes, we performed a targeted systematic review of melatonin metabolism pathways in the human brain and liver. Using two-sample Mendelian randomization (MR), we assessed the causal effects of metabolism pathways and/or individual genes on major depressive disorder (MDD) and nine symptom subtypes derived from Patient Health Questionnaire-9 (PHQ-9). Instrumental variables (IVs) were expression quantitative trait loci (eQTL) for eight individual genes, one synthesis route, and three degradation routes. Results were assessed using Bayesian colocalization and phenome-wide association analyses. At the pathway-level, the genetically proxied synthesis-route signal was associated with PHQ-9 Assessment 5 (PHQ9A5, OR: 0.89, 95% CI: 0.85-0.93), but sensitivity analyses suggested this association was primarily driven by TPH1 and may reflect serotonin-related biology. In contrast, higher brain melatonin degradation raised the risk of both PHQ9A1 (OR: 1.03, 95% CI: 1.02-1.04) and PHQ9A7 (OR: 1.03, 95% CI: 1.02-1.03). Within degradation, up-regulation of the kynurenine sub-pathway increased the odds of PHQ9A3 (OR: 1.05, 95% CI: 1.02-1.07), PHQ9A4 (OR = 1.04, 95% CI: 1.02-1.06) and PHQ9A7 (OR: 1.05, 95% CI: 1.02-1.07). Gene-level analyses were largely concordant, except for SULT1A1, whose higher expression was genetically protective for PHQ9A3 but risk-increased for PHQ9A1 and PHQ9A4. Overall, these results demonstrate that melatonin metabolism exerts symptom-specific and pathway-specific causal effects on depression. A stratified view of melatonin's role may help optimize the application of exogenous melatonin supplementation.

Melatonin↗

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

Exercise-induced chronic adaptations and pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in patients with depression: A systematic review and exploratory meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a leading cause of disability worldwide. Although exercise has been shown to alleviate depressive symptoms, potentially by affecting the body's inflammatory response, evidence in this area remains inconsistent. This study synthesized the most recent evidence from randomized controlled trials (RCTs) on the relationship between exercise-induced chronic adaptations and pro-inflammatory cytokine levels in patients with depression. METHODS: Eligible RCTs were identified from six electronic databases. Effect sizes were pooled using mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Two independent researchers assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: The review included 21 RCTs involving 1572 participants, six of which were included in the meta-analysis. No evidence of efficacy was observed for the chronic effects of exercise on the levels of the pro-inflammatory cytokines interleukin-1-beta (IL-1β) (MD = -0.01, 95% CI [-0.06, 0.04], p = 0.79), interleukin-6 (IL-6) (SMD = -0.30, 95% CI [-0.64, 0.04], p = 0.08), and tumor necrosis factor-alpha (TNF-α) (SMD = -0.18, 95% CI [-0.50, 0.14], p = 0.27) in patients with depression. However, the pooled results for certain markers were not robust. The certainty of evidence for each outcome was very low owing to inconsistency, indirectness, and imprecision. CONCLUSIONS: Evidence for exercise improving pro-inflammatory cytokine levels in patients with depression during the chronic phase remains exploratory and uncertain. Well-designed, adequately powered studies incorporating a broader range of immune biomarkers and dynamic multi-time-point assessments are urgently needed to determine whether exercise-induced chronic adaptations can modulate inflammatory pathways in depression.

Humans↗

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Work	Published	Source identifier	Source
Effects of Esketamine on Postoperative Hospital Anxiety and Depression Scale Scores in Patients Undergoing Laparoscopic Radical Resection for Colorectal Cancer.	2026-09-11	PMID 42723442	pubmed
Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.	2026-08-28	PMID 42637150	pubmed
Patient-reported outcome measures for depression or anxiety symptoms in patients with cardiovascular disease: A COSMIN systematic review.	2026-08-27	PMID 42664848	pubmed
Fyn signaling in the medial prefrontal cortex regulates resistance to stress-induced object recognition impairments in male rats.	2026-08-24	PMID 42636955	pubmed
Effects of acute inflammatory challenge on anhedonia and social reward processing: A randomized controlled trial of endotoxin.	2026-08-20	PMID 42641253	pubmed
Exploring the dose-response relationship between prenatal exercise and postpartum depression: A systematic review and meta-analysis of randomized controlled trials.	2026-08-20	PMID 42641368	pubmed
Elastic tape as an add-on strategy to potentiate pulmonary rehabilitation outcomes in nonobese males with moderate-to-very severe COPD: A randomised clinical trial.	2026-08-19	PMID 42614062	pubmed
Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.	2026-08-16	PMID 42623836	pubmed
Short-term aerobic exercise as an adjunct treatment for depression in acute geriatric psychiatry: Results of a randomized controlled trial.	2026-08-14	PMID 42600781	pubmed
Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.	2026-08-12	PMID 42585935	pubmed
Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.	2026-08-12	PMID 42586309	pubmed
Effectiveness and implementation of task-sharing cognitive-behavioral interventions for perinatal mental health: A systematic review and meta-analysis.	2026-08-11	PMID 42628149	pubmed
The effects of mindfulness-based cognitive therapy in the psychological and physical health of cancer patients: A systematic review and meta-analysis.	2026-08-11	PMID 42667881	pubmed
Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial.	2026-08-10	PMID 42575195	pubmed
Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.	2026-08-05	PMID 42556583	pubmed
Genetic evidence for a causal relationship between melatonin metabolism and depression.	2026-07-30	PMID 42532281	pubmed
Psychotherapy vs antidepressants in heart failure: Impact of adherence.	2026-07-30	PMID 42532282	pubmed
Exercise-induced chronic adaptations and pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in patients with depression: A systematic review and exploratory meta-analysis of randomized controlled trials.	2026-07-30	PMID 42556122	pubmed

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