The basis for amine hypotheses in affective disorders. A critical evaluation

A leading hypothesis concerning a biological basis of the affective disorders is that altered metabolism of brain amines may underlie the cause or pathophysiology of these conditions. Features of affective illnesses supporting biological hypotheses include the somatic symptoms, diurnal rhythm, and apparent "endogenicity" of many severe depressions, and evidence of a genetic basis of manic-depressive illness. Development and preclinical study of medical therapies for the disorders substantially supported a relationship between mood-disturbances and neutrotransmitters and stimulated considerable advances in the physiology and pharmacology of central synaptic neurotransmission. Unfortunately, studies of amine metabolism in patients have not provided consistent support for the amine hypotheses. Moreover, these hypotheses have not led to a coherent biological theory of abnormal behavior, to an objective basis for differential diagnosis, or to the rational development of treatments more effective or safer than those known.