SEARCH · Search PubMed

Results for “Difficult-to-treat depression”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

2,899 records · Page 2Linked to original sources

PubMed2026

Promoter Methylation of HOXA5 and NDRG2 in Multiple Myeloma Patients with Renal Impairment.

Renal impairment (RI) is frequently caused by multiple myeloma (MM), which makes clinical care more difficult if renal function deteriorates or renal failure develops. Thus, in this investigation, we looked at the relationship between HOXA5&NDRG2 promoter methylation in MM patients and evaluated their prognostic potential in predicting RI risk in MM patients. This study included 60 control volunteers and 120 MM patients. The promoter methylations of HOXA5&NDRG2 were quantitatively evaluated by real-time PCR (qPCR) after the extraction of gDNA from whole blood and then treated with bisulfite. The promoter methylation percentages of HOXA5&NDRG2 were significantly increased in MM patients (77.16 ± 2.43&45.49 ± 2.16;p < 0.05) when compared to controls (4.47 ± 0.61&3.33 ± 0.31,respectively), in stage II&III patients when compared to stage I patients and in patients with age ≥ 60 years when compared to patients with age < 60 years. While only the methylation percentage of NDRG2 promoter was significantly increased in MM patients with RI (53.61 ± 3.21,p < 0.05) when compared to MM patients without RI (37.37 ± 2.04). Results obtained from ROC curve revealed that both HOXA5&NDRG2 promoter methylation were good diagnostic tools for MM. The NDRG2 promoter methylation was good prognostic biomarker could predict renal while HOXA5 promoter in the prediction of MM staging. The Kaplan-Meier survival test showed that patients with higher HOXA5&NDRG2 promoter methylation had a shorter OS and a worse prognosis. Only NDRG2 promoter hypermethylation was significantly associated with the risk of RI development in MM patients. HOXA5&NDRG2 promoter hypermethylation may have roles in the molecular etiology of MM and could be used as a treatment regimen.

Humans↗

PubMed2026

Rhinoplasty Difficulty Scale: Development and Psychometric Analysis of a Surgeon's Assessment of Rhinoplasty Technique and Nasal Deformity Correction.

BACKGROUND: Rhinoplasty surgeons lack a universal scale of the relative difficulty of rhinoplasty techniques and rhinoplasty deformities. OBJECTIVE: To compare the expert opinion of the difficulty of rhinoplasty techniques and rhinoplasty deformities among international rhinoplasty surgeons, as measured by a scale of difficulty. METHODS: A cross-sectional survey of rhinoplasty surgeons collected training levels, experience, case volume, and perceived expertise. Rhinoplasty techniques/deformities (n = 64) were rated from 1-10, representing the least to most technically demanding. Rasch analysis was used to examine the fit of the observed data to Rasch model requirements, assess rating scale functioning, and provide estimates of internal consistency. RESULTS: Respondents (n = 63) were in practice (<5 years, 14%; 5-10, 20%; 10-20, 20%; 20-30, 26%; >30, 20%), and rhinoplasty volume ranged from <25 (14%) to >100 cases/year (32%). Self-reported expertise was comfortably novice (32%), intermediate (10%), advanced (28%), and expert (30%). Otolaryngology (42%), facial plastic surgery (30%), and plastic surgery (28%) were represented. Rasch estimates of internal consistency reliability were excellent (0.96 for surgeons and 0.99 for items); the item difficulties were more heterogeneous (mean: 0, SD: 1.23) than the distribution of surgeons (mean: -0.09, SD: 0.58). Survey items were ordered by difficulty, ranging from least difficult (inferior turbinate reduction = 1.01) to most difficult (contracted nose repair post-infection = 8.24). CONCLUSION: The newly developed Rhinoplasty Difficulty Scale provides ratings of common rhinoplasty techniques and deformities with a high correlation among experts using this rating scale.

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

Short-term psychodynamic psychotherapy for functional neurological disorder: A pilot randomized controlled trial.

BACKGROUND: Evidence-based psychotherapeutic treatments for Functional Neurological Disorder (FND) remain limited. This pilot trial evaluated the preliminary efficacy of Short-term Psychodynamic Psychotherapy (STPP) plus Standard Medical Care (SMC) compared with SMC alone in reducing FND symptom frequency. METHODS: Adults with FND were randomized (1:1) to receive either SMC alone or 12 weekly sessions of STPP plus SMC. The primary outcome was symptom frequency (days with symptoms in the last 4 weeks) assessed at the end of treatment (3 months) and at 6-month follow-up. Secondary outcomes included treatment response (≥50% reduction in symptom frequency) and scores on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). RESULTS: Of 91 randomized patients (mean age 38.2 years, 75.8% female), 81.3% completed follow-up. Intention-to-treat analysis using Linear Mixed Models showed that STPP plus SMC significantly reduced symptom frequency compared with SMC alone (estimated mean difference -5.72 [95% CI -8.68 to -2.77]; Cohen's d = 0.77; p < 0.001).Treatment response was achieved by 65.8% in the intervention group versus 16.7% in controls (OR 8.21 [95% CI 2.79-24.19]; p < 0.001; NNT 2.0).Significant improvements were also observed for depression (HAM-D: estimated mean difference -10.80; d = 1.45), anxiety (HAM-A: -7.94; d = 1.06), and disability (WHODAS 2.0: -5.77; d = 0.74), all p < 0.001. CONCLUSIONS: STPP was associated with clinically meaningful improvements in FND symptom frequency and all secondary outcomes, with large effect sizes and high treatment response rates. These findings support the preliminary efficacy of STPP for FND and justify larger, multicenter confirmatory trials.

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

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↗

PubMed2026

Immune dysregulation in depression and psychosis: summary of current evidence and future perspectives.

Despite compelling epidemiological, genetic and cellular evidence linking immune dysregulation to depression and schizophrenia (and other psychotic disorders), causality remains contested and no immune biomarker has yet demonstrated robust clinical utility. Emerging methodological approaches - from target trial emulation on observational data to functional genomics - offer a potential path towards precision immunopsychiatry and stratified immunomodulatory treatment.

Neuroimmunology↗

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

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.

Female↗

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

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

The relationship between composite dietary antioxidant index and odds of depression: A systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: Recently, the association between the composite dietary antioxidant index (CDAI) score and depression has received special attention from researchers. However, this possible association has not been comprehensively examined. Thus, the present study aims to comprehensively assess the relationship between CDAI score and depression odds. METHODS: A thorough literature search was performed using Scopus, PubMed, and Web of Science up to November 2025. Observational studies assessing the relationship between CDAI score and depression odds were included. The odds ratios (ORs) and their 95% confidence intervals (CIs) reported in each study were extracted, and a pooled effect size was calculated using a random-effects model with inverse-variance weighting. RESULTS: Four observational studies were included in the current systematic review and meta-analysis. The pooled effect size indicated that a higher CDAI score was associated with lower odds of depression (OR:0.62; 95%CI: 0.51-0.76, I2 = 48.5%; P-value = 0.121). In an exploratory linear dose-response analysis based on two eligible studies, no significant association was observed between a one-unit increase in CDAI score and the odds of depression (OR = 0.96; 95% CI: 0.91-1.02; I2 = 92.2%; P-value<0.001). Given the limited number of studies and substantial heterogeneity, these findings should be interpreted cautiously. CONCLUSIONS: Our findings suggest that higher CDAI scores, reflecting greater adherence to antioxidant-rich dietary patterns, are associated with lower odds of depression.

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

Distress Intolerance, Social Anxiety, and Depressive Symptoms in Adolescents: Evidence from Random-Intercept Cross-Lagged Panel and Cross-Lagged Panel Network Analyses.

Social anxiety and depressive symptoms frequently co-occur during adolescence, yet the mechanisms underlying their longitudinal associations remain insufficiently understood. Distress intolerance has been proposed as a transdiagnostic risk factor implicated across internalizing symptoms. However, it remains unclear whether distress intolerance is predicted by social anxiety and depressive symptoms, as well as the underlying mechanisms among these three constructs. The specific symptoms most centrally involved in these cross-domain associations remain poorly understood. The present study investigated the longitudinal associations among distress intolerance, social anxiety, and depressive symptoms using a dual-method framework combining random-intercept cross-lagged panel models (RI-CLPM) and cross-lagged panel network (CLPN) analyses. A total of 1,378 Chinese adolescents (Mage = 12.57, SDage = 0.63; 50.4% female) were assessed at three time points with six-month intervals between waves. The RI-CLPM analyses revealed that higher distress intolerance prospectively predicted subsequent increases in both social anxiety and depressive symptoms, whereas elevated social anxiety and depressive symptoms in turn predicted subsequent increases in distress intolerance. Moreover, distress intolerance mediated the longitudinal associations between social anxiety and depressive symptoms. Additionally, distress intolerance was also indirectly associated with its own subsequent levels through social anxiety and depressive symptoms. The CLPN analyses revealed that fear of negative evaluation and fatigue were the strongest predictors of other network nodes from T1 to T2 and from T2 to T3, respectively. In contrast, distress intolerance symptoms were predominantly predicted by other nodes in both cross-lagged networks. These findings extend prior views of distress intolerance as a unidirectional vulnerability by showing that distress intolerance is also predicted by social anxiety and depressive symptoms and accounts for part of their longitudinal associations across adolescence.

Humans↗

PubMed2026

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans↗

PubMed2026

Determinants of Nonspecific Response to Treatment in Randomized Controlled Trials of Major Depressive Disorder: A Narrative Review.

The design, conduct, and interpretation of double-blind randomized placebo-controlled clinical trials in major depressive disorder (MDD) are complicated by determinants of nonspecific response to treatment (NSRT). This narrative review provides a comprehensive overview of the determinants of NSRT in randomized controlled trials (RCTs) for MDD, including the placebo effect, factors related to measurement of the primary endpoint, the inclusion of misdiagnosed patients, the relapsing-remitting course of MDD, and factors related to functional unblinding. Potential strategies to reduce the impact of the determinants of NSRT and to improve the interpretation of RCT outcomes in MDD are also summarized. These strategies include use of centralized rating and standardized rater training, independent diagnostic confirmation, optimized site selection, minimizing financial incentives, exclusion of subjects participating in multiple clinical trials, exclusion of patients with unstable major depressive episode trajectories, and use of active placebo and alternative trial designs. Uniformity among experts in the definitions of determinants of NSRT and related concepts, as well as in strategies to address them, may facilitate progress in the development of novel treatments for MDD.

Humans↗

PubMed2026

Facilitating Thought Progression via a Gamified Mobile Application for Depression: Possible Mediators of Outcomes.

Mobile health interventions represent a scalable and accessible alternative to traditional therapy, which often is out of reach due to high costs and societal stigma. Rumination is considered a key mechanism of emotional disorders and represents a potential treatment target for digital health interventions. The current study investigated the role of rumination as a mediator of the reduction in depression and anxiety reported after the use of a gamified mobile app based on the Facilitating Thought Progression (FTP) framework. One hundred-one adults with mild to moderate depression were randomized to the FTP intervention or a waitlist control group and completed weekly assessments of depression, anxiety, and rumination over 8 weeks. Multilevel structural equation modeling revealed that reduction in rumination significantly mediated decreases in depression and anxiety in the intervention group but not in the waitlist condition. These findings suggest that the FTP app targeted rumination and further highlights its role as a critical target for interventions for depression and anxiety.

Adult↗

PubMed2026

Depression and amyloid-β across CSF, PET, and plasma biomarkers: a systematic review and meta-analysis.

Alzheimer's disease is increasingly defined by biomarker evidence of amyloid-β and tau pathology, sharpening questions about whether late-life depression contributes to, or instead reflects, this pathology. We conducted a systematic review and meta-analysis of studies published between 2000 and 2025 that compared amyloid-β biomarkers in adults with and without depression, with depression defined by validated clinical diagnoses or symptom rating scales. Twenty-four studies were included, spanning three biomarker sources: cerebrospinal fluid, positron emission tomography imaging, and plasma. Across all sources, the pooled difference in amyloid-β burden between depressed and non-depressed individuals was small and clustered near zero, indicating only a weak, statistically non-significant tendency toward higher amyloid in depression. When the three sources were examined separately, each yielded a similar near-null result, although between-study heterogeneity was considerable for cerebrospinal fluid and plasma and moderate for imaging. Importantly, a prespecified subgroup analysis showed that imaging results diverged by quantification method: studies using the simpler standardized uptake value ratio clustered around zero, whereas the smaller group of studies using kinetic distribution volume ratio modelling showed a significant positive association, suggesting that methodological choices critically influence the observed relationship. Taken together, these findings indicate that depression is not consistently accompanied by greater amyloid-β burden across widely used biomarker platforms. The distribution volume ratio signal nonetheless raises the possibility of subtle associations that cruder methods may obscure, and suggests that depression may shape Alzheimer's disease trajectories more by modifying the clinical impact of amyloid than by altering its amount.

Humans↗