Cholinergic mechanisms in affective disorders. Future directions for investigation.

Advances in clinical and basic research methodology combined with clearly articulated concepts create new opportunities for researching the roles of cholinergic mechanisms in the pathophysiology of affective disorders. Areas for study include: roles of cholinergic mechanisms in mediating effects of stress and cholinergic mechanisms linking the pathophysiologies of affective and panic disorders, use of pharmacologic agents to produce cholinergic system supersensitivity in modeling biologic aspects of affective illness, use of multigenerational intrapedigree studies of cholinergic markers associated with affective disease, research into the neurobiology of lithium and ECT as they pertain to muscarinic cholinergic mechanisms, study of the interrelationship of sodium, calcium and lithium ion metabolism and their relationship to cholinergic-monoaminergic interaction, the development of brain imaging strategies and techniques, e.g., positron emission tomography (PET), to measure changes in cholinergic receptor density and affinity as a function of clinical state, identification and validation of a peripheral model of the central muscarinic receptor, study of the pharmacology of abusable substances and its relationship to mechanisms regulating mood, affect, psychomotor function and other variables related to the affective disorders, and development of in vitro and in vivo models useful in studying the physiology and biochemistry of the interaction of cholinergic and monoaminergic neurons. These models may allow us to bridge the traditional cholinergic and monoamine hypotheses of affective disorders.