Brain Age in Major Depressive Disorder: Genetic and Environmental Risk and Resilience Factors from the ENIGMA MDD consortium

COEX 

Recent research revealed a connection between major depressive disorder (MDD) and a higher brain age, potentially shedding light on the increased risk of premature mortality in individuals with MDD. However, brain aging and MDD are both individually complex phenomena, highlighting the important need to further dissect the nature and direction of their connections. If we can develop a deeper understanding of the etiology and drivers of biological aging in MDD, we can potentially develop early-intervention strategies to target underlying mechanisms. Progress in this field has been hampered by methodological heterogeneity. To further establish reliable connections between genetics, brain imaging phenotypes and behavior, it is imperative to employ large sample sizes. In my talk, I will share insights from a global research study involving >3,400 participants, providing ample statistical power to study multidimensional imaging phenotypes, genetic, and environmental factors. We have adopted standardized protocols for calculating polygenic risk scores and extracting imaging-derived data in 11 cohorts comprising 1,810 individuals with MDD from 4 different countries. I will discuss findings on age-related brain signatures and a wide range of polygenic risk scores (e.g., MDD, BMI, C-Reactive Protein), environmental exposures (e.g., childhood trauma, smoking) and protective factors (e.g., education). Finally, I will explore the relationship between brain age and other indicators of biological aging (i.e., epigenetic clocks).