Sex-specific disease-associated modules for depression

Abstract

A recent study reveals sexually dimorphic disease-associated gene-expression modules and hub genes in postmortem brains from female and male individuals with depression. These modules are conserved in mouse models of depression.

Figure 1

Sex-specific gene-expression modules in depression. Schematic for the analysis of gender-specific depression-related modules in individuals with MDD and stressed mice. RNA-seq analysis was conducted on the indicated regions of the postmortem brains of women and men with depression and those of controls, and on female and male mice exposed to chronic variable stress. Network analysis reveals sex-specific networks across brain regions and identifies disease-related gene modules in women and men that overlap with chronic-stress-related modules in female and male mice. Manipulation of key hub genes in the top-ranked expression modules (decreased Dusp1 in female mice and increased Emx1 in male mice) produces convergent effects on neuronal activity in vmPFC and causes depressive behaviors, but only when these genes are manipulated in the corresponding female or male mice. OFC, orbital frontal cortex; NAc, nucleus accumbens; aINS, anterior insula; vSub, ventral subiculum; dlPFC, dorsolateral prefrontal cortex; vmPFC, ventromedial prefrontal cortex.