INTENSIFICATION OF THE CENTRAL SEROTONINERGIC PROCESSES AS A POSSIBLE DETERMINANT OF THE THYMOLEPTIC EFFECT

It is suggested that in depression the production of tryptophane pyrrolase by the liver is stimulated by raised blood-corticosteroid levels, and the metabolism of tryPTophane is shunted away from serotonin production, and towards kynurenine production.

Abstract

Psychic depression may result from deficiency of brain serotonin. It is suggested that in depression the production of tryptophane pyrrolase by the liver is stimulated by raised blood-corticosteroid levels. As a result the metabolism of tryptophane is shunted away from serotonin production, and towards kynurenine production. Blood-corticosteroid levels are raised in depression as a consequence of excitement of the amygdaloid complex, on which serotonin is normally an inhibitory influence. Thus, whatever the order of events, a vicious circle is set up. It is suggested that the actions of the various antidepressant treatments in use have a common mechanism—namely, the intensification of the central serotoninergic processes. The thymoleptic action of imipramine-like tricyclic antidepressants results from potentiation of serotoninergic effects on the brain; these effects include inhibition of the amygdala, which suppresses central mechanisms of stress normally manifested in anxiety, tension, and fear. The mood-elevating component of the antidepressant actions of monoamine-oxidase inhibitors and of electroconvulsive therapy is related to the increase in brain serotonin levels. Activation of central adrenergic mechanisms is responsible for psychoenergetic and motor-stimulating effects of antidepressants, but not for their mood-elevating actions.