Cholinergic-monoaminergic interaction in the pathophysiology of the affective disorders?

Cholinergic and monoaminergic hypotheses have dominated affective disorders research. The propriety of an hypothesis is determined by the point of a field in its development. Both categories of hypotheses have encouraged important research but their utility can be limited by the assumption that the pathophysiology of depression and mania is due to cholinergic or monoaminergic pathology. In actuality, neurotransmitter networks interact and are mutually regulating. The cholinergic-monoaminergic interaction theory (CMIT) is a dynamic account of the mutual inter- and intra-regulation of cholinergic, noradrenergic, dopaminergic and serotonergic systems in the pathophysiology of affective disorders. This model maintains that virtually every variable related to the neurobiology of bipolar disorder is regulated by mechanisms internal and external to those neurotransmitter systems involved in its pathophysiology. In principle, these variables include receptor density and sensitivity, membrane properties, cytosolic calcium, magnesium and sodium ion concentrations, activities of ATPases and calcium channel gating and cascade mechanisms. This array of variables stems from the assumption that the brain is a complex, unified dynanism. The CMIT posits homeostatic mechanisms preserving the direction of this dynanism. In this article, the theme of neurotransmitter-neurotransmitter system interaction is developed and the CMIT is offered as a paradigm useful in addressing the pathophysiology of affective disease from within the conceptual framework of a neurotransmitter system interaction theory.