The effects of childhood abuse on the brain: moderation by genetic vulnerability factors
06 / 2008 - 06 / 2013
Childhood abuse, including emotional, physical, and sexual abuse, is a major public health problem that affects 10-20% of the population. It is increasingly acknowledged that there is a wide variation in individual responses to childhood abuse, which is (at leat in part) related to genetic vulnerability factors. In vulnerable individuals, childhood abuse may result in a broad range of psychopathological disorders (including depression and posttraumatic stress disorder), involving dysfunctions in affect and memory. The first aim of the present proposal is to investigate the impact of childhood abuse on brain structures and functions related to affect and memory across a variety of mood disorders. Because of the large individual variation in responses to stress, the second aim is to elucidate genetic vulnerability factors (related to MR/GR-genes and BDNF) that may moderate the effects of childhood abuse on brain structures and functions. The third aim is to investigate dysregulations in stress reactivity (including the HPA-axis) and emotional responsivity in vulnerable genotypes. The first two aims will be investigated in a large (NESDA) cohort of 2,850 individuals with a range of psychopathology (e.g., from no, to mild, and severe anxiety and depression) and adverse childhood experiences. To further elucidate the processes that may mediate the effects of childhood abuse, experimental studies measuring physiological and emotional stress reactivity will be conducted in genetic vulnerable individuals. By applying a multidisciplinary approach, important knowledge will be acquired on how genetic vulnerability factors moderate neurobiological, neuroendocrinological, and cognitive responses to childhood abuse. Such an integrative, transdiagnostic approach is very much needed to increase our understanding of the specific pathways underlying maladaptive changes related to childhood abuse. These insights may in turn help to advance our knowledge on the treatment and prevention of these adverse effects.