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PubMed2025

ADHD in Youth With Major Depressive Disorder in the Texas Youth Depression and Suicide Research Network (TX-YDSRN): Clinical Correlates and Moderators.

OBJECTIVE: Depression is a major public health concern with a 19% lifetime prevalence in youth, often precipitating other concerns, including suicidal behavior, poor school performance, and worsened peer relationships. ADHD is also common among youth and frequently presents alongside major depressive disorder (MDD), with this comorbidity associated with increased impairment. More research is needed to elucidate the clinical characteristics of this comorbidity (MDD + ADHD), especially as it relates to youth with MDD and no ADHD (MDD - ADHD). The present study examined the clinical correlates of MDD + ADHD in youth and the presence of an ADHD diagnosis as a moderator of the relationship between depressive symptoms and suicidality, peer relationships, and school functioning, respectively. METHODS: Our sample included 797 youth with MDD ages 8 to 20 years (Mage = 15.5 years) with and without ADHD. RESULTS: Youth with MDD + ADHD experienced more severe depressive symptoms, higher levels of suicidality, impulsivity, and irritability, and worse academic performance compared to those with MDD - ADHD. ADHD diagnosis did not moderate the relationships between depression severity and suicidality, peer relationships, or school functioning, respectively, suggesting that having an ADHD diagnosis may not affect these outcomes in depressed youth in this way. CONCLUSION: Findings shed light on the impact of ADHD in depressed youth, which may allow for earlier and more tailored intervention efforts aimed at identifying and targeting depression, suicidality, peer relationships, and school functioning.

Humans↗

PubMed2026

Acupuncture improves depressive symptoms and prefrontal cortical function in mild to moderate depressive disorder: A randomized sham-controlled trial and fNIRS study.

BACKGROUND: Depressive disorder is a common mental illness associated with substantial functional impairment. Although pharmacotherapy is widely used, its effectiveness is often limited by adverse effects and poor adherence. Acupuncture has been increasingly applied as a complementary treatment for depression, and its neurobiological characteristics remain unclear. OBJECTIVE: This randomized, sham-controlled trial aimed to evaluate the clinical efficacy of acupuncture for mild to moderate depressive disorder and to investigate its effects on prefrontal cortical function using functional near-infrared spectroscopy (fNIRS). METHODS: Patients with mild to moderate depressive disorder were randomly assigned to a real acupuncture (RA) group or a sham acupuncture (SA) group and received standardized treatment for 8 weeks. Clinical outcomes were assessed using the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Short Form-36 Health Survey (SF-36), and a traditional Chinese medicine syndrome score. A subset of participants underwent fNIRS assessment during resting-state and task-based conditions to evaluate prefrontal cortical activation and functional connectivity. RESULTS: Compared with baseline, the RA group showed significant reductions in SDS and SAS scores and significant improvements in SF-36 emotional domains, with effects emerging at Week 4 and persisting up to 12 weeks after treatment. Improvements were greater and more stable in the RA group than in the SA group. fNIRS analyses revealed enhanced activation in dorsolateral and medial prefrontal regions and strengthened prefrontal functional connectivity following acupuncture, whereas neural changes in the SA group were limited. CONCLUSION: Acupuncture is effective for improving depressive and anxiety symptoms and quality of life in patients with mild to moderate depressive disorder. Modulation of prefrontal cortical activation and connectivity may underlie its antidepressant effects.

Humans↗

PubMed2026

Effects of adjunctive bifrontal tDCS on depressive symptoms and cognitive performance in major depressive disorder: A randomized, double-blind, sham-controlled crossover pilot study.

BACKGROUND: Evidence for antidepressant effects of transcranial direct current stimulation (tDCS) in major depressive disorder (MDD) is heterogeneous, and cognitive effects remain uncertain. We compared depressive symptoms and DSST performance during active and sham bifrontal tDCS in medicated outpatients with MDD and baseline HAMD-17 ≥ 15. METHODS: In this randomized, double-blind, sham-controlled crossover pilot trial, adults with MDD and inadequate response to an adequate antidepressant trial were assigned to active→sham or sham→active tDCS sequences while continuing antidepressants. Each period comprised 10 sessions over 2 weeks. Active stimulation was delivered at 2 mA for 20 min (anode F3, cathode F4); sham used the same montage with brief ramping only. No washout interval was used. No washout interval was used. The primary outcome was HAMD-17; secondary outcomes were DSST and CGI ratings. RESULTS: Of 38 randomized participants, 32 completed both periods and were analyzed per protocol. HAMD-17 scores were lower during active than sham stimulation (mean difference -3.63, 95% CI -5.86 to -1.40; p = 0.002), but the condition-by-sequence interaction was significant (p = 0.026). No condition effect was observed for DSST (p = 0.261) or CGI-Severity (p = 1.000); CGI-Improvement was strongly sequence-dependent (p < 0.001). In an exploratory first-period analysis, adjusted T1 HAMD-17 scores were lower in the active-first group (adjusted difference -4.90, 95% CI -7.92 to -1.87; p = 0.003). Adverse effects were mild and transient. CONCLUSIONS: Active tDCS was associated with lower HAMD-17 scores, but the pooled contrast was order-dependent and cannot be interpreted as a definitive treatment effect. No DSST benefit was observed.

Humans↗

PubMed2026

A genome-wide investigation of depression among individuals with and without irritability.

Individuals presenting with both depression and irritability may constitute a different group of individuals with respect to those presenting without irritability, but their biological differences remain unknown. We aimed to identify genetic variants associated with depression among individuals with and without irritability, highlight biological pathways, and test for genetic associations with other traits. We conducted a genome-wide association study (GWAS) using data from the UK Biobank (N = 487,409). We identified a group of individuals presenting with depression and reporting never having experienced irritability (depression without irritability, n = 35,857, 11.8%), and another with depression and reporting having experienced irritability (depression with irritability, n = 23,613, 8.1%) and compared them to controls with no depression or irritability (n = 268,012). The GWAS of depression without irritability identified 2 SNPs which reached genome-wide significance (P < 5×10-8; rs72795440 and rs1233494). The GWAS of depression with irritability (NGWAS = 292,485) identified 3 SNPs reaching genome-wide significance (rs2815748, rs102275, and rs7227069). When comparing SNPs between depression phenotypes, 15 SNPs had significantly different effect sizes. Patterns of genetic correlation with 44 complex traits were overall similar between the 2 depression phenotypes, with the highest genetic overlap observed with anxiety for depression without irritability (rg = .77) and neuroticism for depression with irritability (rg = .76). This study shed light into common and distinct biological factors characterizing depression among individuals with and without irritability and contribute to better understanding the genetic architecture of depression to potentially inform treatment and personalized medicine.

Humans↗

PubMed2026

Effects of lavender oil preparation silexan on different symptoms of major depression - results from a randomized, controlled trial.

BACKGROUND: Major depressive disorder (MDD) is characterized by depressed mood, anhedonia, and loss of energy, which can be accompanied by associated symptoms and co-morbidities. Psychiatric scales such as the Montgomery Åsberg Depression Rating Scale (MADRS) must account for the complex nature of depression. METHODS: The MADRS total score change between baseline and week 8 was the primary outcome measure in a randomized, double-blind clinical trial investigating the antidepressant efficacy of 8 weeks' treatment with silexan compared to sertraline and placebo in patients with mild or moderate MDD. We report on a pre-planned, exploratory analysis of the individual MADRS items. Treatment effects were assessed using analyses of covariance with baseline adjustment, based on an estimand strategy. RESULTS: 498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan was superior to placebo for 5 out of the 9 MADRS items analyzed ("apparent sadness", "reported sadness", "reduced appetite", "concentration difficulties", "lassitude"; P < .05) and showed clinically important adjusted mean value differences >0.2 points for 7 out of the 9 items. Item-level results for silexan and sertraline were mainly comparable. CONCLUSIONS: Silexan had a strong over-all antidepressant effect, with the most pronounced improvements affecting the cardinal symptoms of depression. TRIAL REGISTRATION: EudraCT2020-000688-22 first entered on 12/08/2020. Significance statement Patients with depressive disorders can show many different symptoms. To better characterize the clinical action of an antidepressant, it is therefore important to analyze not only the overall value of a depression scale but also the individual items that describe these symptoms. Silexan is a preparation from lavender oil whose antidepressant effect has been proven in a randomized, double-blind, placebo-controlled 8-week study in patients with mild or moderate major depressive disorder. Based on the individual items of the Montgomery Åsberg Depression Rating Scale that was used as the main outcome for efficacy, we found in an exploratory, hypothesis-generating analysis that silexan had a rather broad antidepressant effect in the participants of our study, with potentially clinically meaningful advantages over placebo for 7 out of the 9 individual items investigated. This applied in particular to the main symptoms of depression, namely sadness and lassitude. Our single-item analysis thus helps to understand the antidepressant effects of silexan in more detail. Significant outcomes In patients with mild to moderate major depressive disorder, lavender oil preparation silexan has a clinical profile similar to that of the selective serotonin re-uptake inhibitor sertraline based on an item-level analysis of the Montgomery-Åsberg Depression Rating Scale (MADRS). Silexan has a significant antidepressant effect that includes an alleviation of depressed mood, anhedonia, and loss of energy, the cardinal symptoms of depression. The broad improvement of symptoms of depression could not be explained by the proven anxiolytic efficacy silexan alone but indicates an independent, direct antidepressant effect. The present item-level analysis provides valuable and detailed additional insights into the therapeutic profiles of silexan and sertraline and may help clinicians to tailor antidepressant treatment to the specific symptoms of a patient. Limitations For item-level analyses of the MADRS, no validated thresholds for the assessment of the clinical importance of changes over time have been defined, taking into account that different items may have different thresholds. Even though our analyses were pre-defined, they were exploratory and did not include studywise type I error level control. Their generalizability beyond the study population is therefore limited.

Humans↗

PubMed2026

Exploring the hypothetical role of Bacteroides species in depression progression: insights from metagenomic analysis.

Depression, a psychiatric disorder with significant morbidity and mortality, has a complex etiology. Recent advances in microbiome research have highlighted the potential role of fecal microbiota in depression pathogenesis. This study utilized shotgun metagenomic sequencing to compare the fecal microbiota of 28 depression patients and 26 healthy individuals. Significant differences in fecal microbiota composition were observed between the two groups. We generated 350 non-redundant high-quality metagenome-assembled genomes (MAGs) by binning and conducted comparisons between the depression and control groups. Notably, we found that the MAGs enriched in people with depression mostly belonged to Bacteroides, indicating a close link between Bacteroides abundance and the development of depression, suggesting that Bacteroides might be a potential culprit for depression. In the depression group, we found that the module of nitric oxide synthesis was remarkably enriched, and all Bacteroides MAGs contained genes annotated as nitric oxide synthase, suggesting that increased levels of Bacteroides may contribute to elevated nitric oxide synthesis. A distinct microbial signature consisting of Arthrobacter sp._U41, Bacillus cereus, Campylobacter rectus, and Pasteurella dagmatis accurately discriminates between depressed individuals and healthy controls, achieving an average area under the receiver operating characteristic curve of 0.950. This research sheds light on the potential role of fecal microbiota in depression and highlights specific metabolic pathways and microbial markers for further investigation.IMPORTANCEThis research highlighted significant differences in the composition and function of fecal microbiota between individuals with depression and healthy individuals, particularly the enrichment of Bacteroides metagenome-assembled genomes (MAGs) in depression patients. The upregulation of the nitric oxide synthesis pathway associated with these MAGs belonging to Bacteroides in the gut of depression patients had also been observed. The selected bacterial biomarkers reliably differentiate depression cases from healthy controls with high diagnostic accuracy (mean area under the receiver operating characteristic curve = 0.950). Our results suggest the importance of exploring microbial markers as potential diagnostic and therapeutic targets in managing depression.

Humans↗

PubMed2026

Genotype-Guided Antidepressant Prescribing for Patients With Depression: A Randomized Clinical Trial.

IMPORTANCE: The effectiveness of pharmacogenetics to guide prescribing of selective serotonin reuptake inhibitors (SSRIs) for depression remains unclear, despite the well-established association between SSRI pharmacokinetics and genetic variation. OBJECTIVE: To determine whether pharmacogenetic-guided prescribing of SSRIs improves treatment response in patients with depression. DESIGN, SETTING, AND PARTICIPANTS: The ADOPT PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) Depression pragmatic randomized clinical trial was conducted from August 10, 2021, through April 27, 2024, at primary care, psychiatry, or family medicine clinics at enrolling sites throughout the US. Patients were aged 8 years or older and had experienced depression for 3 months or longer. INTERVENTION: Patients were randomized to genotype-guided SSRI prescribing (intervention group) or usual care (control group). Actionable drug metabolism phenotypes were defined as those for which pharmacogenetic clinical guidelines recommend alternative medication selection or dose adjustment. MAIN OUTCOMES AND MEASURES: The primary outcome was change in Patient-Reported Outcomes Measurement Information System (PROMIS) depression T scores at 3 months among patients with the actionable phenotype. Secondary end points included adverse effect severity of SSRIs at 3 months and depression remission (measured with PROMIS depression scores and Patient Health Questionnaire-8 [PHQ-8] scores) at 6 months. RESULTS: This study of 1460 patients included 1239 adults (84.9%) (mean [SD] age, 40.6 [16.7] years) and 221 children (15.1%) (mean [SD] age, 14.6 [1.8] years). Most patients were female (1096 [75.1%]). A total of 692 patients (47.4%) had an actionable phenotype; 351 (50.7%) were assigned to the intervention, and 341 (49.3%) were assigned to usual care. At baseline, 463 of the 692 patients (66.9%) reported having depressive symptoms for more than 2 years, 603 (87.1%) were receiving pharmacologic treatment, and 354 (51.2%) were receiving nonpharmacologic treatment. At 3 months, no significant differences were observed between the intervention and usual care groups in change in PROMIS depression T scores (mean [SD] change, -4.3 [8.4] vs -4.0 [8.1]; P = .68), medication adverse effect burden (mean [SD] change, 8.2 [4.3] vs 7.8 [4.5]; P = .37), or Patient Health Questionnaire-8 score change (mean [SD] change, -3.3 [5.2] vs -2.7 [4.8]; P  = .13). However, at 6 months, the PROMIS depression T-score remission rate (score ≤16) was higher in the intervention group compared with the usual care group (153 of 317 patients [48.3%] vs 122 of 310 patients [39.4%]; P = .02). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, genotype-guided prescribing of SSRIs did not improve control of depression symptoms at 3 months compared with usual care but was associated with higher depression remission rates at 6 months. These findings suggest a possible longer-term clinical benefit and indicate that future studies should focus on the durability and long-term impact of genotype-guided prescribing in the management of depressive symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT04445792 (Master Protocol Research Program platform trial) and NCT05966155 (ADOPT PGx Depression trial).

Humans↗

PubMed2026

Depressive Symptoms and Smoking Cessation Among Adolescents and Young Adults Who Smoke: A Prospective Cohort Study.

PURPOSE: This study examined the bidirectional prospective associations between depressive symptoms and smoking cessation among adolescent and young adults who smoke. METHODS: Data on 1,151 participants aged ≤25 years who smoke and receive peer-led quitline counseling in Hong Kong (2016-2022) were analyzed. Exposures included baseline depressive symptoms and smoking cessation (self-reported 7-day abstinence) at 1, 3, and 6 months; Outcome measures included smoking cessation at 1, 3, and 6 months and depressive symptoms at 6 months. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, with a score ≥16 indicating at risk for depression. RESULTS: More severe baseline depressive symptoms were associated with lower odds of smoking cessation at 1, 3, and 6 months, which reversely was associated with lower depressive symptoms at 6 months (all p < .05). Similarly, being at risk for depression at baseline was associated with lower odds of smoking cessation at 1 (adjusted odds ratio [aOR] .66, 95% confidential interval [CI] .47-.93) and 3 months (aOR .71, 95% CI .52-.97). Conversely, smoking cessation at 1 (aOR .40, 95% CI .23-.69), 3 (aOR .58, 95% CI .37-.92), and 6 months (aOR .44, 95% CI .29-.69) was associated with lower odds of at risk for depression at 6 months. DISCUSSION: More severe depressive symptoms were prospectively associated with lower odds of smoking cessation, while smoking cessation was associated with lower depressive symptoms and risk for depression. Integrated interventions simultaneously addressing psychological needs and smoking are warranted, when delivered in smoking cessation programs or embedded within mental health services for youth who smoke.

Humans↗

PubMed2026

Altered EEG microstate dynamics reflect depressive symptoms in temporal lobe epilepsy.

BACKGROUND: Depressive symptoms are a common and disabling comorbidity in temporal lobe epilepsy (TLE), yet the neural mechanisms linking seizure networks to affective symptoms remain unclear. Although limbic network dysfunction has been implicated in both epilepsy and depressive disorders, it is unknown whether the time-varying dynamics of large-scale electrophysiological brain states reflect depressive symptom severity in TLE. In this study, we examined whether EEG microstate dynamics capture network alterations associated with depressive symptoms in individuals with unilateral TLE. METHODS: We analyzed resting-state, visually normal scalp EEG from 26 individuals with unilateral TLE. EEG microstates were identified by clustering global field power peaks into four canonical classes, with electrode positions mirrored to align the ictal hemisphere across subjects. Microstate dwell time, fractional occupancy, global transition entropy, and Markov transition probabilities were quantified and related to Beck Depression Inventory-II (BDI) scores. RESULTS: Individuals with high depressive symptoms (BDI ≥ 13; N = 12) exhibited longer mean dwell time in the ictal hemisphere-aligned microstate compared with individuals with low depressive symptom burden (BDI < 13; N = 14). Across subjects, dwell time in this microstate correlated with depressive symptom severity (r = 0.57, p = 0.002). TLE individuals with higher depressive symptoms exhibited reduced global transition entropy (p = 0.02), which also correlated with depressive symptom severity (r = -0.54, p = 0.004), indicating decreased flexibility of microstate transitions. Despite similar fractional occupancy of this state between groups, individuals with higher depressive symptoms were less likely to transition into the ictal hemisphere-aligned microstate from non-ictal or posterior configurations. Once engaged, however, the ictal-aligned microstate showed increased persistence, indicating prolonged stabilization of this network configuration. CONCLUSION: Higher depressive symptom burden in unilateral TLE is associated with increased temporal rigidity of the ictal hemisphere-aligned brain microstate, reflecting impaired disengagement of epileptogenic network configurations. These findings suggest that depressive symptoms in TLE may be associated with epilepsy-related disruptions in large-scale neural dynamics.

Humans↗

PubMed2026

Risk of mortality and complications in people with depressive disorder and co-occurring diabetes mellitus: a systematic review and meta-analysis.

AIMS: People with depressive disorder have increased premature mortality and higher rates of diabetes mellitus than general population. Evidence shows that diabetes may further increase their risk of premature death from diabetes-related complications, especially cardiovascular diseases (CVDs). Earlier studies examining depression-associated outcomes in diabetes patients have shown mixed results and were hindered by important limitations, especially the use of self-reported questionnaires to ascertain depression, causing misclassification bias by identifying subclinical symptoms or diabetes distress. Associations of depression with specific diabetes complications have not been systematically evaluated. This meta-analysis aimed to investigate the risk of mortality and complications among patients with depression and co-occurring diabetes (depression-diabetes group) relative to patients with diabetes-only (diabetes-only group), on their all-cause mortality rates, and if applicable cause-specific mortality rates, and occurrence of specific diabetes complications. METHODS: We systematically reviewed and quantitatively synthesized diabetes-related outcomes in patients with depression by searching Embase, MEDLINE, PsycInfo and Web-of-Science from inception to 20 December 2024, and included studies that examined mortality and complication outcomes in depression-diabetes group relative to diabetes-only group. Results were synthesized by random-effects meta-analytic models, with stratified-analyses (subgroup analyses and meta-regression) by study-level characteristics, including age, gender, study period, geographic region, follow-up duration and nature of diabetes sample. The study was registered with PROSPERO (CRD42024595145). RESULTS: Twenty-six studies were identified from nine geographic regions. Regarding mortality risk, depression-diabetes group exhibited increased risks of all-cause mortality (RR = 1.30 [95% CI: 1.21-1.39]) and CVD-specific mortality (1.15 [1.02-1.29]) relative to diabetes-only group. Regarding complication risk, depression-diabetes group showed increased risk of complications (1.28 [1.18-1.40]) relative to diabetes-only group, especially in incident-diabetes sample signifying advanced disease stage upon presentation, with stratified-analyses showing higher risk of metabolic complications (1.63 [1.33-1.99]) and cardiovascular complications (1.20 [1.11-1.29]), and lower likelihood of retinopathy (0.84 [0.76-0.94]), albeit comparable rates of cerebrovascular complications (1.36 [0.99-1.87]), nephropathy (1.09 [0.93-1.27]) and peripheral-vascular complications (0.97 [0.79-1.18]). Both overall mortality and complication risks were present in various regions and persisted over time. Heterogeneities were noted and could not be entirely explained by stratified analyses. CONCLUSIONS: Our study demonstrated that patients with depression and co-occurring diabetes were associated with elevated overall mortality risk and complication risk (particularly metabolic and cardiovascular-complications) than non-depressed counterparts, suggesting an overall poorer glycemic control that might eventually drive their earlier death. Comprehensive and multipronged interventions are needed for individualized risk estimation of diabetes-related outcomes, with consequent early interventions to minimize the avoidable physical morbidity and premature mortality in this vulnerable population.

Humans↗

PubMed2025

A Systematic Review of Quantitative Studies of Depression and Loneliness in Black Women with Hypertension in the United States.

INTRODUCTION: Hypertension disproportionately affects Black women with subsequent complications that can extend beyond physical health. Notably, there is a significant relationship between hypertension, depression, and loneliness, with hypertensive Black women more likely to exhibit symptoms of depression. Since loneliness and social isolation are predictors of depression, recognizing and addressing these interconnected health concerns could improve patient outcomes and quality of life. This systematic review presents a synthesis of findings on depression screening practices, depression symptoms, and loneliness in quantitative studies of Black women with hypertension in the United States. METHODS: Using the EbscoHost platform, a comprehensive literature search for studies measuring depression and loneliness in Black women with hypertension was conducted. The following databases were selected: Medline Complete, CINAHL Complete, APA PsychArticles, and PsychINFO. RESULTS: Twenty-three articles were included; 16 focused on depression, and these studies highlighted a significant burden of depression in this demographic compared to their counterparts. Five studies reported loneliness and its relation to depression and hypertension. Loneliness and social isolation, as independent risk factors, exacerbated symptoms of depression and contributed to the onset and progression of hypertension. Two prior reviews corroborated these findings. Studies have emphasized the role of trust in clinical interactions and the importance of appropriate therapeutic interventions. DISCUSSION: Black women with hypertension are at a heightened risk for symptoms of depression, compounded by feelings of loneliness. Loneliness and depression are linked to physiological stress, contributing to hypertension. These problems are underrecognized and undertreated across populations, and this lack of recognition and treatment contributes to health inequity.

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

Genetic heterogeneity affects the risk of incident depression, comorbidity, and response to environment: A prospective trajectory study.

BACKGROUND: Depression exhibits significant heterogeneity in its genetic underpinnings. The role of genetic components in the development of depression and its comorbidities remains insufficiently explored. METHODS: First, depression risk loci from a large-scale genome-wide meta-analysis were annotated to Gene Ontology (GO) terms by functional enrichment. GO-based polygenic risk scores (GO-PRS) were then calculated for individuals in the UK Biobank. Principal component analysis (PCA) was applied for dimensionality reduction, followed by cluster analysis to identify genetic subtypes of depression. Multistate models were applied to assess the impact of genetic patterns on the trajectory from healthy status to incident depression, and depression to 26 subsequent diseases, as well as the associations between environmental factors and disease trajectories across genetic subtypes. RESULTS: Participants were categorized into three genetic subtypes: immune-dominant, neuro-dominant, and comprehensive-risk. Significant differences in risk of depression and subsequent diseases, and susceptibility to environmental factors were observed across subtypes. Comprehensive-risk subtype showed higher risks of depression compared to immune-dominant (HR: 1.10, 95% CI: 1.05-1.15) and neuro-dominant subtype (HR: 1.12, 95% CI: 1.08-1.16). Comprehensive-risk subtype exhibited higher risks of transition from depression to subsequent diseases, such as anemia compared to immune-dominant subtype, and diseases of the digestive system compared to neuro-dominant subtype. Environmental factors were more strongly associated with the transition from depression to subsequent diseases in immune-dominant and comprehensive-risk subtypes, including cardiovascular, respiratory, and metabolic diseases. CONCLUSIONS: Our findings highlight the genetic heterogeneity of depression and comorbidities, and shed light on how genetic components modulate responses to environmental factors.

Humans↗

PubMed2026

Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-Response Relationships and Moderating Factors.

OBJECTIVE: This meta-analysis evaluated the efficacy of behavioral activation (BA) in adolescents with subthreshold depression (SD) or major depressive disorder (MDD), exploring dose-response relationships and moderating factors. METHOD: We searched PubMed, EMBASE, Web of Science, EBSCO, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) through December 31, 2024. Risk of bias was assessed using RoB-2, and evidence quality with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Analyses were performed with R, using standardized mean difference (SMD) for continuous variables and meta-regression for dose-response relationships. Subgroup analyses included symptom severity, intervention setting, delivery format, and parental involvement. The primary outcome was the reduction in depressive symptoms (PROSPERO: CRD42023444273). RESULTS: A total of 14 studies were included (11 RCTs meta-analyzed, comprising 572 participants). BA demonstrated a moderate effect size compared to treatment-as-usual (SMD = -0.42) and a large effect size compared to no-treatment controls (SMD = -0.87). BA was more effective for mild depressive symptoms (SMD = -0.93) than severe symptoms (SMD = -0.43), with significant efficacy in university settings (SMD = -0.94). Intervention without parental involvement exhibited significantly larger effects than those with parental participation (SMD = -0.94 vs -0.38; p < .0001), although this finding was likely confounded by age, symptom severity, and intervention setting. BA moderately improved both behavioral activation levels and functioning (SMD = 0.49). CONCLUSION: Short-term, school-based BA is significantly beneficial for older adolescents with mild depressive symptoms. Findings provide practical guidance for optimizing BA implementation and highlight directions for future research, including the need for larger sample sizes, standardized follow-up assessments, and more representative samples. PLAIN LANGUAGE SUMMARY: This meta-analysis evaluated the effectiveness of behavioral activation (BA), a therapeutic approach focused on improving positive activities, in adolescents with subthreshold depression or major depressive disorder. Based on 14 included studies and 572 participants, BA was found to be more effective for subthreshold compared to major depression. These findings suggest a promising role for BA as an early intervention tool in adolescent depression. STUDY REGISTRATION INFORMATION: Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-response Relationships and Moderating Factors; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023444273. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group.

Humans↗

PubMed2025

Artificial Intelligence in Diagnosing Depression Through Behavioural Cues: A Diagnostic Accuracy Systematic Review and Meta-Analysis.

AIM: To synthesise existing evidence concerning the application of AI methods in detecting depression through behavioural cues among adults in healthcare and community settings. DESIGN: This is a diagnostic accuracy systematic review. METHODS: This review included studies examining different AI methods in detecting depression among adults. Two independent reviewers screened, appraised and extracted data. Data were analysed by meta-analysis, narrative synthesis and subgroup analysis. DATA SOURCES: Published studies and grey literature were sought in 11 electronic databases. Hand search was conducted on reference lists and two journals. RESULTS: In total, 30 studies were included in this review. Twenty of which demonstrated that AI models had the potential to detect depression. Speech and facial expression showed better sensitivity, reflecting the ability to detect people with depression. Text and movement had better specificity, indicating the ability to rule out non-depressed individuals. Heterogeneity was initially high. Less heterogeneity was observed within each modality subgroup. CONCLUSIONS: This is the first systematic review examining AI models in detecting depression using all four behavioural cues: speech, texts, movement and facial expressions. IMPLICATIONS: A collaborative effort among healthcare professionals can be initiated to develop an AI-assisted depression detection system in general healthcare or community settings. IMPACT: It is challenging for general healthcare professionals to detect depressive symptoms among people in non-psychiatric settings. Our findings suggested the need for objective screening tools, such as an AI-assisted system, for screening depression. Therefore, people could receive accurate diagnosis and proper treatments for depression. REPORTING METHOD: This review followed the PRISMA checklist. PATIENTS OR PUBLIC CONTRIBUTION: No patients or public contribution.

Humans↗

PubMed2026

Peripheral immune markers and choroid plexus volumes as predictors of change in depressive symptoms: Insights from the EMBARC study.

Changes in choroid plexus (ChP) volume and peripheral inflammation have been associated with Major Depressive Disorder (MDD), yet their individual and combined impact on depressive symptoms is unclear. This study investigated whether baseline immune markers and ChP volumes predict changes in depressive symptoms during the 8-week treatment period among Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study participants who received either sertraline or placebo. Adults (n = 222) with MDD with peripheral blood samples were included. Circulating chemokines and cytokines were examined using a 40-plex assay. Depressive symptoms were assessed over 8 weeks using the Hamilton Depression Rating Scale (HAMD-17). Principal component analysis (PCA) was used for dimension reduction. Mixed-effects models were used to examine whether immune profiles and ChP volumes, and their interaction predicted HAMD-17, adjusting for demographic/clinical covariates and baseline depression severity. PCA identified three immune profiles. One profile, characterized by higher levels of cytokines and chemokines including IL-6, TNF-α, and IL-1β, was associated with greater depression severity, higher BMI, age, and CRP at baseline. Higher levels of these immune markers were associated with less improvement in depressive symptoms at 8 weeks (estimate = 1.211, p = 0.018) in models adjusting for right and left ChP volume (right ChP model: estimate = 1.034, p = 0.005; left ChP model: estimate = 0.993, p = 0.007). Interactions between immune markers and ChP volumes were not significant. Future investigations are warranted to examine the relationships between immune markers and ChP volume beyond structural changes in the context of depression symptoms.

Adult↗

PubMed2025

Effectiveness of physical activity intervention for depression, anxiety and comorbid symptoms during the perinatal period among Chinese primiparas.

BACKGROUND: To examine the effectiveness of a physical activity (PA) programme incorporating partner support and enjoyment in preventing perinatal depression, anxiety, and comorbid anxiety and depression (CAD) among Chinese primiparas. METHODS: A total of 120 eligible primiparas were randomised into intervention or control groups. The intervention group received the 13-week PA programme and the control group received the usual care. The outcomes were depression, anxiety, and CAD assessed at baseline, post-intervention, and 6 weeks after delivery. Differences were examined using generalised linear mixed models with intention-to-treat. RESULTS: A significant group × time interaction was observed for depression score, anxiety score, anxiety incidence, and CAD incidence (all p < 0.05). However, no significant interaction was found for depression incidence. Compared to the control, the intervention substantially reduced the scores of depression (MD: -2.67 (-4.16 to -1.17); -2.63 (-4.15 to -1.11)) and anxiety (MD: -4.95 (-9.23 to -0.67); -7.33 (-11.85 to -2.82)), as well as the rates of depression (OR: 0.40 (0.18 to 0.85); 0.44 (0.21 to 0.93)) and CAD (OR: 0.35 (0.14 to 0.87); 0.26 (0.11 to 0.62)) at post-intervention and 6-week postpartum. Notably, anxiety incidence showed significant reduction only at 6-week postpartum (OR: 0.34 (0.16 to 0.74)) (all p < 0.05). Within the intervention group, no significant changes occurred in most outcomes from baseline to post-intervention and 6-week postpartum, except depression scores (MD:-1.60 (-2.79 to -0.41); -1.23 (-2.44 to -0.03); p < 0.05). CONCLUSIONS: The PA programme (including partner support and enjoyment) may be effective in reducing perinatal depression, anxiety and CAD among primiparas.

Adult↗

PubMed2026

Toward personalized interventions for preventing depression in primary care: Qualitative and quantitative findings from the e-predictD pilot study.

BACKGROUND: The predictD intervention, delivered by family physicians (FPs), has demonstrated effectiveness and cost-efficiency in preventing depression and anxiety. The e-predictD study aims to design, develop, and evaluate a novel personalized intervention for depression prevention by integrating information and communication technologies (ICTs), risk prediction algorithms, and decision support systems (DSS) for both patients and FPs. OBJECTIVE: To evaluate the satisfaction, usability, and acceptability, of a beta version of the e-predictD intervention in primary care settings. METHODS: The e-predictD intervention follows a biopsychosocial approach, including an initial patient-FP interview, specific FP training, and an app. A β-version was tested in a pilot study without a control group over three months. The app integrates a validated depression risk prediction algorithm, decision algorithms, and a monitoring system supporting the DSS. The DSS generates a personalized prevention plan (PPP) from eight intervention modules: physical exercise, social relationships, problem-solving, communication skills, decision-making, assertiveness, sleep improvement, and cognitive restructuring. Patients and FPs discussed the PPP in a 15-minute baseline interview, selecting modules for implementation over three months. Semi-structured interviews gathered feedback. Assessments included depression (PHQ-9), anxiety (GAD-7), quality of life (SF-12), and major depression risk (predictD algorithm). RESULTS: Six FPs from six Spanish cities enrolled 56 non-depressed patients at moderate-to-high risk of depression; 47 (84%) completed follow-up. The app was used for a median of six days (interquartile range: 1-30). Both FPs and patients expressed satisfaction, leading to incorporated improvements. After three months, significant reductions in major depression risk and anxiety symptoms were observed, alongside improved mental quality of life. However, no significant changes were found in depressive symptoms or physical quality of life. CONCLUSION: This pilot study supports the feasibility and acceptability of the e-predictD β-version, despite lower-than-expected app usability. Health improvements were observed, warranting confirmation in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03990792.

Adult↗