Recent Advances in the Neurobiology of Depression

Elucidation of the neurobiological basis of depression and other mood disorders is rapidly increasing. Considerable experimental and clinical evidence supports the fundamental roles of serotonin and norepinephrine, as well as the interactions between these systems in the etiology of depression. Substantial evidence has accrued, including changes in neurotransmitter and neurotransmitter metabolite concentrations, reuptake sites, and receptors, to support the hypothesis that alteration in neuronal serotonergic and noradrenergic function occurs in the central nervous system of patients with major depression. Serotonin and norepinephrine represent the major targets of current therapeutic interventions, which may induce longer-term adaptive changes via modulation of the activity of these neurotransmitters. In addition, two neuropeptide neurotransmitters—substance P and corticotropin-releasing factor—have been implicated in the pathophysiology of mood disorders. Preliminary studies have reported the clinical efficacy of a tachykinin NK1 receptor antagonist and a CRF1 receptor antagonist in depressive disorders. Further clarification of the precise neurobiological changes occurring in depression has implications for the use and development of novel effective treatments for this disorder.