This article reviews human and animal studies in the neurobiology of depression. The etiology of the illness, associated neurotransmitter dysregulation, sex steroids, the role of stress, and sleep regulation are discussed. It is suggested that the genesis of depression is related to homeostatic maladaptation that is sexually dimorphic. The authors propose that depressed females are hyperresponsive to stress, whereas depressed males are hyporesponsive to stress. This divergence reflects the exaggeration of naturally occurring differences between males and females, which are most obvious under challenge conditions. The authors conclude that future work in this area should fully evaluate sexual dimorphism, neural plasticity, critical periods, and individual differences in vulnerability.
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