Genetic influence on brain volume alterations related to self-reported childhood abuse

Abstract

As an important predictor of adulthood psychopathology, self-reported childhood abuse appears heritable and is associated with brain abnormalities. However, the specific genetic mechanisms behind these brain alterations remain largely unknown. This study recruited young adults who reported different degrees of childhood abuse from the community. In order to fully understand the influence of genes on brain changes related to self-reported childhood abuse, various experiments were conducted in this study. Firstly, volume changes of gray matter and white matter related to childhood abuse were investigated by using advanced magnetic resonance imaging techniques. After sequencing the whole exons, we further investigated the relationship between polygenic risk score, brain volume alterations, and childhood abuse score. Furthermore, transcription-neuroimaging association analysis was used to identify risk genes whose expressions were associated with brain volume alterations. The gray matter volumes of left caudate and superior parietal lobule, and white matter volumes of left cerebellum and right temporal lobe-basal ganglia region were significantly correlated with the childhood abuse score. More importantly, brain volume changes mediated the influence of polygenic risk on self-reported childhood abuse. Additionally, transcription-neuroimaging association analysis reported 63 risk genes whose expression levels were significantly associated with childhood abuse-related brain volume changes. These genes are involved in multiple biological processes, such as nerve development, synaptic transmission, and cell construction. Combining data from multiple perspectives, our work provides evidence of brain abnormalities associated with childhood abuse, and further indicates that polygene genetic risk and risk gene expression may affect the occurrence of childhood abuse by brain regulation, which provides insights into the molecularpathology and neuromechanism of childhood adversity. Paying attention to the physical and mental health of high-risk children may be a fundamental way to prevent childhood abuse and promote lifelong mental health.