Experiential and genetic contributions to depressive- and anxiety-like disorders: Clinical and experimental studies

Stressful events have been implicated in the precipitation of depression and anxiety. These disorders may evolve owing to one or more of an array of neuronal changes that occur in several brain regions. It seems likely that these stressor-provoked neurochernical alterations are moderated by genetic determinants, as well as by a constellation of experiential and environmental factors. Indeed, animal studies have shown that vulnerability to depressive-like behaviors involve mechanisms similar to those associated with human depression (e.g., altered serotonin, corticotropin releasing hormone and their receptors, growth factors), and that the effects of stressors are influenced by previous stressor experiences, particularly those encountered early in life. These stressor effects might reflect sensitization of neuronal functioning, phenotypic changes of processes that lead to neurochernical release or receptor sensitivity, or epigenetic processes that modify expression of specific genes associated with stressor reactivity. It is suggested that depression is a life-long disorder, which even after effective treatment, has a high rate of re-occurrence owing to sensitized processes or epigenetic factors that promote persistent alterations of gene expression. (C) 2008 Elsevier Ltd. All rights reserved.