ArticleDevelopmental cell2026
Environmental and genetic risk factors of depression converge on neuronal dysfunction driven by changes in cholesterol homeostasis.
Article in Developmental cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- The role of metabolic disorders in major depressive disorder.Molecular biology reports · 2026Review
- Genetic associations and candidate functional genes linking depression and obesity: a multi-omics integrative study.Frontiers in genetics · 2026Article
- Metabolic risk stratification and psychotic symptoms in first-episode drug-naïve major depressive disorder: a principal component-based cross-sectional study.Frontiers in psychiatry · 2026Article
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9 authors.
Funding
Abstract
Major depressive disorder (MDD) is a complex, multifactorial neuropsychiatric disorder influenced by both genetic and environmental factors, but how these factors impact human neuronal function remains unclear. Using a highly defined human pluripotent stem cell (hPSC)-based prefrontal cortex (PFC) platform, we examined three high-confidence environmental and genetic factors associated with depression: chronic exposure to high levels of cortisol or interferon alpha (IFN-a), and a mutation in SIRTUIN 1 (SIRT1). All three conditions induced overlapping phenotypes of neuronal dysfunction, characterized by dendritic atrophy, synaptic loss, and neuronal hypoactivity across multiple cell lines. RNA sequencing uncovered converging alterations in neuronal cholesterol homeostasis. Depleting cholesterol in control neurons reproduced core depression-associated neuronal phenotypes, while cholesterol supplementation was sufficient to rescue these phenotypes in depression-associated conditions. These findings point to cholesterol imbalance as a common driver of neuronal dysfunction in MDD, linking diverse genetic and environmental risk factors through a shared cellular pathway.
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