Project 466740

Major depressive disorder (MDD) or depression is a psychiatric disorder, which is twice as prevalent in women relative to men. The impact of biological sex on gene expression in the brain may partially explain this disparity. Studies have revealed that while some of the gene expression changes associated with depression are shared between men and women, most are completely distinct. Based on shared genes, our group recently developed a transcriptome-based polygenic risk score (tPRS), which is a number that reflects the likelihood of an individual having depression based on the genes that are being expressed in their brain. A higher tPRS has been associated with changes in the folding of the outer layer of the brain (cortical folding) in brain regions associated with depression. Cortical folding patterns form early in development and remain relatively stable in adulthood, suggesting that depression-associated patterns may emerge early in life and eventually lead to depressive symptoms. Since depression-associated gene expression is different between the sexes, it is important to study the changes specific to females as early as childhood and adolescence to understand depression in girls and women, who are disproportionately affected by the disease. Therefore, we propose to develop a female-specific tPRS (tPRS-F) which incorporates the gene expression profile uniquely associated with depression in females. We further propose to establish its association with depression vulnerability and cortical folding in adolescent girls. This novel tPRS-F can then be used to predict vulnerability to depression in female individuals early enough to facilitate the development of effective personalized interventions to counteract the burden of depression in girls and women.