The pervasive and persistent neurobiological and clinical aftermath of child abuse and neglect.

anxiety disorders in individuals exposed to child abuse and neglect. Space constraints preclude a comprehensive discussion, and reviews are available. 5,6 Here, we will summarize clinical studies that have sought to elucidate the biological mechanisms by which early life trauma produces these long-lasting effects on psychiatric disease morbidity. The major areas to be discussed include genetics and epigenetics, neuroendocrine systems, and inflammation, as well as structural and functional brain imaging. It is important to note that in addition to increasing risk for major psychiatric disorders, child abuse and neglect, not surprisingly, also affect treatment response. For example, in a recent meta-analysis, Nanni et al 7 reported that depressed patients with a history of child abuse or neglect exhibited a significantly reduced response to both antidepressants and psychotherapy. The pioneering study by Caspi and colleagues 8 documented the importance of a polymorphism in the promotor region of the serotonin transporter in mediating the depressogenic effects of child abuse and neglect in the well-studied Dunedin cohort. This finding has been replicated by most (including our group 9), but not all, 10 investigators. A multitude of studies have now documented the importance of polymorphisms of several candidate genes in mediating the depressogenic, suicidogenic, and/or anxiogenic effects of child abuse and neglect. These include studies of the corticotropin-releasing factor (CRF) type 1 receptor (CRFR1),