BioProject

In humans there are sex-specific differences in the prevalence and symptomology of psychiatric disorders. However, preclinical animal models have primarily used males. As such, the molecular mechanisms underlying sex-specific differences in mental illness are not well established. In this study, we compared transcriptome-wide gene expression profiles in male and female rats within the corticolimbic system, including the cingulate cortex, nucleus accumbens medial shell (NAcS), ventral dentate gyrus and the basolateral amygdala. We found a considerable number of differentially expressed genes (DEGs) between males and females across all brain regions. However, 84.9% of all DEGs were found in the NAcS (> 5000 genes; p < 0.01, FDR < 0.01). Relating these DEGs to genome wide association studies (GWAS) revealed an enrichment for loci associated with major depressive disorder (Psychiatric Genomics Consortium 2019). We compared the DEGs in the NAcS to an analgous human dataset (Labonte, 2017), and found 587 common DEGs which were enriched for genes associated with both anxiety (neuro genetics study, 2016) and broad depression (UK biobank, 2018). Our data provide comprehensive evidence of sex molecular profiles in the NAcS. Importantly these differences associate with anxiety and depression, suggesting an intrinsic molecular basis for sex-based differences in disease prevalence and presentation. Overall design: RNA sequencing of brain regions of male and female rats