Theories of Biological Etiology of Affective Disorders

This chapter discusses evidence relating to the catecholamine hypothesis, and then briefly reviews the work on steroids and electrolyte metabolism, focusing on findings of etiological, rather than descriptive, significance.

Abstract

The existence of effective physical and pharmacological treatments of mania and depression provides an important avenue for investigation into the etiologies of these disorders. It is germane to consider the modes of discovery of the antimanic and antidepressant drugs, as well as their etiological implications. The body of data on electrolyte and steroid alterations in the affective disorders is then discussed, focusing on findings of etiological, rather than descriptive, significance. This chapter discusses evidence relating to the catecholamine hypothesis, and then briefly reviews the work on steroids and electrolyte metabolism. The discovery of the therapeutic effects of the monoamine oxidase (MAO) inhibitors in the treatment of depression and the discovery of the antihypertensive and antipsychotic effects of reserpine stimulated work by basic scientists in elucidating the pharmacological action of these drugs. The most likely mechanism of action of the MAO inhibitors was the inhibition of the enzyme monoamine oxidase, an enzyme which breaks down biogenic amines, such as norepinephrine and serotonin. Reserpine interferes with the storage of these amines in intracellular storage vesicles. Hence, monoamine oxidase inhibitors raise the brain levels of biogenic amines in many species (by inhibiting their degradation) while reserpine depletes the brain of these amines. The fact that these drugs either produce or relieve depression and alter amines in opposite ways suggested that perhaps both mania and depression may be caused by alterations in biogenic amine metabolism.