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Twin Study Finds No Broad Cytokine Link to Depression or Alcohol Use Disorder

Photoreal illustration of cytokine molecules and brain imagery, conveying inflammation-depression hypothesis under scrutiny.

The broad cytokine story failed its most direct community test: in 972 adults, depression, alcohol use, and alcohol use disorder (AUD) were not associated with C-reactive protein (CRP) or a pre-registered pro-inflammatory cytokine index. The only multiple-testing-corrected cytokine hits ran opposite the hypothesis — AUD was linked to lower IL-1β, IL-4, IL-10, and IL-12 — …

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PGx Testing Found Actionable Genotypes in 30% of Veterans

MHD featured image for pharmacogenomic testing in veteran depression and antidepressant polypharmacy.

A 12-week randomized pilot trial in 60 Veterans with depression and psychiatric polypharmacy found that 30% had an actionable antidepressant gene-drug interaction, but immediate access to pharmacogenomic results did not clearly change prescribing or Patient Health Questionnaire-9 depression scores compared with delayed access.1 Research Highlights Actionable PGx results were common: 18 of 60 Veterans, or …

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Resistance Exercise Linked to Lower Depression and Anxiety in Korean Adults

A 2026 nationwide Korean analysis found that resistance exercise was associated with lower depression and anxiety scores after propensity score matching, while aerobic exercise alone was not significantly associated with either outcome. The result favors adding weights, bands, machines, or body-weight strength work to mental-health exercise advice without assuming that lifting caused the lower symptom …

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TRD MRI Coupling Classified Depression Resistance Above 0.88 AUC

A 2026 multimodal MRI study found that treatment-resistant depression had lower coordination between brain structure and brain activity than non-treatment-resistant depression in frontal, parietal, motor, and temporal regions. Machine-learning models using those structure-function coupling measures classified treatment-resistant vs. non-treatment-resistant depression with AUC values from 0.886 to 0.950 in the primary atlas analysis.1 Research Highlights TRD …

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Esketamine Failed Cost-Effectiveness vs. Cheaper TRD Options at $50K/QALY

Photoreal illustration of a depression-treatment decision with cost and outcome imagery, conveying healthcare-economic decision-making.

Intranasal esketamine — FDA-approved for treatment-resistant depression in 2019 — failed cost-effectiveness benchmarks against four cheaper third-line options in a 2026 Hong Kong modeling study, with incremental cost-effectiveness ratios (ICERs) of US$134,127 to US$312,750 per quality-adjusted life-year (QALY) at a US$50,000/QALY willingness-to-pay (WTP) threshold.1 Combination antidepressant therapy was the most cost-effective strategy modeled. Research Highlights …

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SSRI Pharmacogenomic Testing: CYP2D6, CYP2C19, Remission

MHD featured image for SSRI Pharmacogenomic Testing: CYP2D6, CYP2C19, Remission.

A 2026 methylome-wide association study by Shen et al. found 48 CpG methylation sites tied to the quadratic CYP2C19 metabolizer-status term in 18,396 Generation Scotland participants, with 19 sites showing non-linear patterns and targeted replication in 1,238 older adults.1 That supports CYP2C19 as real biology beneath SSRI pharmacogenomics, but it does not prove universal antidepressant …

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Subcallosal Cingulate DBS for Treatment-Resistant Depression

MHD featured image for Subcallosal Cingulate DBS for Treatment-Resistant Depression.

A 2026 systematic review of subcallosal cingulate (SCC) functional connectivity found 28 qualifying resting-state fMRI studies in depression: 21 rTMS/iTBS studies, 4 ECT studies, 3 focused-ultrasound studies, and 0 DBS or tDCS studies.1 That number is the useful correction: SCC DBS may still be biologically plausible, but the current fMRI connectivity literature mostly explains noninvasive …

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