Microstructural Correlates of Resilience against Major Depressive Disorder: Epigenetic Mechanisms?

Mental disorders are a major cause of long-term disability and are a direct cause of mortality, with approximately 800.000 individuals dying from suicide every year worldwide - a high proportion of them related to major depressive disorder (MDD)^1^. Healthy relatives of patients with major depressive disorder (MDD) are at risk to develop the disease. This higher vulnerability is associated with structural^2-4^ and functional brain changes^5^. However, we found using high angular resolution diffusion imaging (HARDI) with 61 diffusion directions that neuron tracts between frontal cortices and limbic as well as temporal and parietal brain regions are characterized by better diffusion coefficients in unaffected relatives (UHR), who managed to stay healthy, compared to healthy volunteers without any family history for a psychiatric disease (HC). Moreover, those UHR with stronger fibre connections better managed incidences of adversity in early life without later developing depression, while in HC axonal connections were found to be decreased when they had early-life adversity. Altogether these findings indicate the presence of stronger neural fibre connections in UHR, which seem to be associated with resilience against environmental stressors, which we suggest occur through epigenetic mechanisms