The neurobiological toll of child abuse and neglect

Abstract

Exposure to interpersonal violence or abuse affects the physical and emotional well-being of affected individuals. In particular, exposure to trauma during development increases the risk of psychiatric and other medical disorders beyond the risks associated with adult violence exposure. Alterations in the hypothalamic-pituitary-adrenal (HPA) axis, a major mediating pathway of the stress response, contribute to the long-standing effects of early life trauma. Although early life trauma elevates the risk of psychiatric and medical disease, not all exposed individuals demonstrate altered HPA axis physiology, suggesting that genetic variation influences the consequences of trauma exposure. In addition, the effects of abuse may extend beyond the immediate victim into subsequent generations as a consequence of epigenetic effects transmitted directly to offspring and/or behavioral changes in affected individuals. Recognition of the biological consequences and transgenerational impact of violence and abuse has critical importance for both disease research and public health policy.

FIGURE 1

A schematic representation of the basic physiology of the hypothalamic pituitary adrenal (HPA) axis. When a stress response occurs, corticotrophin releasing factor (CRF) is excreted by the paraventricular nucleus of the hypothalamus (PVN). The release of CRF from the PVN stimulates the release of adrenocortiotropic hormone (ACTH) from the anterior pituitary. When ACTH binds to receptors in the adrenal medulla, glucocorticoids are released into the circulation. Glucocorticoids, cortisol in primates and corticosterone in rodents, bind to receptors in the hippocampus, PVN, and pituitary to modulate the continuance or cessation of the response as well as adaptation. Exposure to chronic stressors, particularly during development, leads to modifications in receptor systems in the HPA axis and thereby hypo- or hyper-active stress responses. Because glucocorticoids also modulate metabolism and immune function, chronic stimulation of the HPA axis can have profound effects on the entire body.

FIGURE 2

The manifestation of psychiatric diseases such as MDD and PTSD is modulated by the interactions of genetics and the environment. Some gene x environment interactions confer resilience while others produce vulnerability. Development is a time of particular susceptibility to negative gene x environment interactions leading to increased risk for manifestation of psychiatric and somatic disorders when exposed to negative environmental conditions prior to the end of adolescence. Epigenetic changes in response to stress exposure are not limited to the exposed individual but are transmitted between generations perpetuating the adverse effects.