We reviewed the evidence for involvement of central cholinergic neurons in affective disorder. Cholinomimetics inhibit speech, thought, and activity in most subjects, decrease manic symptoms and, in some affective disorder patients, produce depressive symptoms. Cholinomimetics also cause ACTH and cortisol secretion and decrease latency to REM sleep. It is unclear whether cholinomimetics are specifically "antimanic" or "depressogenic" or whether their fundamental effect is nonspecific behavioral inhibition; whether the observed effects of cholinomimetics are mediated largely through cholinergic pathways, are secondary to changes in other neurotransmitters or are part of a nonspecific stress response. The suggestion that anticholinergic agents have mood elevating properties has not yet been subjected to controlled investigation. Although the proposal that affective disorders involve cholinergic neurons has received some support from clinical investigation further research is required to substantiate the intriguing observations to date and to clarify the physiologic and psychologic processes mediating them.
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