P300-based support vector machine model for identifying adolescent with first-episode, drug-naïve major depressive disorder.

Parabens exposure, depression, and cardiovascular metabolic health in the elderly: Findings from a cross-sectional study in China.

Behind the scenes of MDD experience: Mood instability and daily function based on real-time monitoring.

Effects of aerobic exercise on core executive function in adults with major depressive disorder: A Systematic review and three-level meta‑analysis.

miR-146a-3p drives major depressive disorder pathogenesis via BDNF suppression: a novel diagnostic and therapeutic target.

Multi-time scale dynamic effective brain networks reveal accelerated brain aging in individuals with major depressive disorder.

Beck observed overgeneralised thinking as a key vulnerability factor for excessive self-blame/-criticism in major depressive disorder (MDD). Whilst the contribution of reduced access to specific autobiographical memory episodes has often been considered, the role of more abstract semantic memory systems remains elusive. Here, we investigated the individual ability to differentiate between the meaning of abstract social concepts when interpreting behaviour (e.g. "critical" vs "fault-finding") and its contribution to vulnerability to self-blaming biases and MDD using a previously developed cognitive task in 96 participants (n = 60 medication-free remitted MDD and n = 36 controls). Of those, 75 participants also completed an fMRI paradigm in which they viewed self- and other-blame emotion-evoking statements. A priori right anterior temporal lobe (ATL) seed and bilateral anterior subgenual cingulate and dorsolateral prefrontal cortex regions-of-interest were defined. As expected, the MDD group exhibited greater self-blame-selective conceptual overgeneralisation and stronger interdependency of conceptual overgeneralisation with negative emotional valence relative to the control group. Individuals with this interdependency showed higher self-blame-selective right anterior subgenual cingulate and primary motor cortex activations across groups, potentially corresponding to stronger self-blame and self-agency attributions, respectively, when conceptually overgeneralising the interpretation of their negative actions. Individuals with higher self-blame-selective conceptual overgeneralisation displayed lower right ATL activation for self- vs other-blame, suggesting reduced access to differentiated conceptual representations. Future studies are needed to confirm the hypothesis that self-blame-selective conceptual overgeneralisation characterises a distinct neurocognitive subtype of primary MDD vulnerability which may be modulated by depressive state and thus serve as a personalised treatment target.

Neural signatures of major depressive disorder with comorbid insomnia: Low gamma PoCG.R-INS.L connectivity as a potential biomarker.

The burden and forecast of major depressive disorder attributed to behavioral risk factors among adolescents and adults at global, regional and national levels from 1990 to 2050: A systematic analysis for GBD 2021.

The increased risk of atherosclerotic diseases (stroke, coronary artery disease [CAD]) observed in depression may stem from shared pathophysiology. We examined whether: 1) major depression (MD) and atherosclerotic traits share genetic risk, and 2) altered gene expression in various tissues linked to shared genetics has a potential causal role in depression etiology. Data from the largest genome-wide association studies of MD (N = 3,887,532) and 8 atherosclerotic traits (N = 26,909-1,308,460) were used in Two-Sample Mendelian randomization and colocalization to detect cross-trait causal associations and genomic loci containing shared causal variants. In shared loci, summary data-based Mendelian randomization estimated the effects of gene expression on MD etiology using expression quantitative trait loci datasets from whole blood, brain and heart tissues and atherosclerotic plaques from the Athero-Express Biobank Study. MD genetic liability increased risk of any stroke (OR=1.15, p = 9.47 × 10-8), ischemic stroke (OR=1.16, p = 1.52 × 10-7), small vessel disease (OR=1.34, p = 4.76 × 10-5) and CAD (OR=1.2, 95 %CIs=1.13-1.26, p = 3.76 × 10-22). Eight genomic regions harbored potentially shared causal variants, including one on chromosome 7 linking MD with any stroke, ischemic stroke and CAD. Altered expression of 16 genes in blood, 10 in brain, and 6 in heart was found causal for MD etiology. In atherosclerotic plaques, one gene was linked to MD at nominal significance only. Major depression and atherosclerotic diseases share genetic risk potentially acting in depression pathophysiology through expression of genes in blood, brain and heart tissues. Involvement of atherosclerotic plaques in depression etiology was not supported. Identified pathways could guide the development of new treatments to prevent depression-heightened atherosclerotic risk.

Therapies for major depressive episodes (MDEs) in major depressive disorder (MDD) and bipolar disorder (BD) have limited efficacy and tolerability. Transcranial electrical stimulation (tES), including transcranial direct current (tDCS), alternating current (tACS), and random noise stimulation (tRNS), has been investigated as a non-invasive alternative, but existing reviews are outdated or narrow in scope. A systematic review of tES modalities for MDE in MDD and BD was conducted, alongside a meta-analysis restricted to tDCS RCTs. Eligible participants had MDD or BD diagnosed per standardised criteria. The primary outcome was change in depression severity; secondary outcomes were response and remission. Moderator and sensitivity analyses were performed post hoc. Thirty-four tES trials met inclusion criteria; 31 used tDCS (n=1833 at endpoint) and were eligible for meta-analysis. Pooled results showed active tDCS produced a moderate reduction in depressive symptoms versus sham (Hedges' g=0.387, 95% CI: 0.192-0.582), with no significant effect on response (OR=1.397) or remission (OR=1.138). Larger effects were observed in bipolar depression, monotherapy samples, and studies using F3/F4 electrode placement. No publication bias was detected. Risk of bias ratings influenced effect sizes. tDCS demonstrates statistical superiority to sham for symptom reduction, but effects do not reliably translate to response or remission, and heterogeneity remains substantial. Efficacy varies by clinical and methodological factors. tDCS is a safe, moderately effective option for MDEs. Future trials should improve methodological rigor, refine montage selection, and evaluate longer or multi-channel protocols.

Treatment-resistant depression (TRD) remains a formidable challenge in psychiatry, with nearly one-third of patients with major depressive disorder (MDD) failing to respond adequately to first-line pharmacological treatments. Pathophysiology in MDD has highlighted the N-methyl-D-aspartate (NMDA) glutamatergic system as a promising therapeutic target. In 2022, the US Food and Drug Administration (FDA) approved the bupropion and dextromethorphan (DXM) combination (BDC), the first oral combination that affects both the NMDA receptor and norepinephrine-dopamine systems. DXM is an uncompetitive NMDA receptor antagonist, and in combination with bupropion, it has been shown to be a rapidly acting oral medication with clinically significant improvement in the first week of treatment. BDC, however, has many inherent limitations such as contraindications in those with eating disorders and a history of seizures. Anxiety is a common comorbidity in MDD, and bupropion has been shown to lack efficacy in treating anxiety. In addition, BDC did not improve cognition. Memantine can treat depression and cognitive impairments concurrently. Fixed-dose combination pills can be less flexible than prescribing each drug separately, as BDC is limited to a 105mg (bupropion)-45mg (DXM) combination. The projected 1-month cost of possible combinations of memantine ($5.00) with a selective serotonin reuptake inhibitor (SSRI, $4.00), serotonin-norepinephrine reuptake inhibitor (SNRI, $15.00), and bupropion ($18.00) are cheaper than BDC ($1119.00). Instead of BDC, we propose various alternatives such as a bupropion-memantine combination or SSRI/SNRI and memantine for MDD/TRD.

Neural mechanisms of rumination subtypes in adolescent major depressive disorder based on large-scale brain network analysis.

Multidimensional characterization of structure aberrations for biotypes of major depressive disorder.

Advancing patient stratification in major depressive disorder: Evaluation of clinical staging and machine learning prediction models based on real-world data.

Reduced serum FGF17 levels are associated with deficits in motivation, pleasure, and expression in antidepressant-free patients with major depressive disorder.

Multimodal EEG study of emotional face processing in major depressive disorder.

Parietal alpha asymmetry as a diagnostic marker for depression and a predictive biomarker for anhedonia improvement after melatonergic antidepressant treatment.

Myelin damage in major depressive disorder: Insights from neuroimaging, molecular mechanisms, and therapeutic perspectives.

Oligodendrocyte dysfunction in major depressive disorder: Mechanistic insights and emerging therapies.