ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Transcriptomic risk scores for attention deficit/hyperactivity disorder.Molecular psychiatry · 2023Pooled it
- Deep learning reveals a neurocomputational mechanism predicting depression risk in adolescents.Science advances · 2026Article
- Polygenic scores in psychiatric research and clinical practice.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- A Novel Polygenic Risk Score Indexing Somatostatin-Expressing Inhibitory Neurons Predicts Somatostatin-Expressing Cell Proportions and Severity of Symptoms in Late-Life Depression.Biological psychiatry global open science · 2026Article
- Association between Cortical Gyrification and Major Depression: Clinical Correlates.Psychopathology · 2026Article
- Neurodevelopmental signature of a transcriptome-based polygenic risk score for depression.Psychiatry research · 2024Article
- A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges.Neuroscience bulletin · 2023Review
- Sex differences of brain cortical structure in major depressive disorder.Psychoradiology · 2023Article
- Polygenic risk for depression and resting-state functional connectivity of subgenual anterior cingulate cortex in young adults.Journal of psychiatry & neuroscience : JPNArticle
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Authors and funding
29 authors at 20 institutions in 7 countries.
Funding
Abstract
Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10
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