A post-mortem investigation of the locus coeruleus- noradrenergic system in resilience to childhood abuse

Childhood abuse (CA) is one of the strongest lifetime predictors of major depressive disorder (MDD) and suicide. However, some individuals exposed to CA are resilient, avoiding the development of psychopathology. Recently, the locus coeruleus-noradrenergic (LC-NE) system has been involved in resilience following stressful events at adulthood. We investigated how a history of CA affects the integrity of the LC-NE system at the molecular and cellular level in human post-mortem brain samples of depressed suicides, and whether differential neurobiological mechanisms can be revealed in resilient individuals. Anatomical analysis revealed that CA-induced MDD and suicide is associated with decrease in LC-NE neurons density. RNA sequencing of laser captured LC-NE neurons highlighted differentially expressed genes, principally in the RES-CA group. Resilience to CA involves specific neurobiological adaptations in the LC-NE system that potentially protect against the loss of LC-NE neurons and the negative long-term outcome of CA-induced depression and suicide. Our results provide insights into potential therapeutic targets for preventing or treating CA-induced MDD.