Brain Cholinergic Systems and the Pathogenesis of Affective Disorders

Extreme and debilitating fluctuations in mood have long been thought to involve chemical imbalances in the central nervous system. The role of catecholamines in the affective disorders has been emphasized since the pioneering work by Schildkraut and Kety (1967) and others, who noted that drugs which elevate mood and which are effective in the treatment of depression facilitate catecholaminergic transmission in the brain, and conversely, that drugs which may produce depression and that are used in the treatment of manic behavior tend to antagonize the synaptic actions of dopamine and norepinephrine. Measurements of catecholamine metabolites in the urine and cerebrospinal fluid of manic and depressed patients have also produced some evidence consistent with the view that depression is associated with reduced catecholaminergic synaptic transmission (Schildkraut, 1973; Schildkraut and Kety, 1967).