The major neuropsychiatric disorders are devastating illnesses that are only modestly responsive to treatment. Improving the treatment of these conditions will require innovative new strategies that depart from previously focused-on pharmacological mechanisms. Considerable preclinical and clinical data indicate corticotropin-releasing factor (CRF) signaling as a target for new psychotropic drug development. Here we review alterations in the CRF system reported in several psychiatric conditions. We also examine the preclinical work that has dissected the distinctive roles of CRF receptors in specific circuits relevant to these disorders. We further describe the clinical trials of CRF1 receptor antagonists that have been conducted. Although these clinical trials have thus far met with limited therapeutic success, the unfolding complexity of the CRF system promises many future directions for studying its role in the etiology and treatment of neuropsychiatric conditions.
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