Persistent central nervous system effects of an adverse early environment: clinical and preclinical studies

In the search for the underlying biological causes of psychiatric disorders, primary roles for both genetics and environment have been clearly established. A family history of mood or anxiety disorders, representing the genetic component, clearly increases the risk for developing these illnesses in adulthood. The pivotal role of early environmental influences in the pathogenesis of these disorders is also supported by an abundance of both clinical and preclinical data. This review will highlight some of the preclinical and clinical literature that suggests early adverse experience may sensitize corticotropin-releasing factor (CRF) circuitry. The neurobiology of depression highlighting the pathophysiological role of CRF is reviewed. Next, some of the preclinical models of early life stress are discussed; along with a review of the relevant clinical literature that suggests that the functional dysregulation of CRF circuitry in response to early life trauma may contribute to adulthood depression. The discussion will be framed in regards to a stress-diathesis model in which early adverse events result in a sensitized stress axis that predisposes individuals to develop mood disorders.