Brain Biogenic Amine Depletion and Mood

To evaluate the hypothesis that clinical depression is associated with reduced brain biogenic amine activity, the behavioral effects, in man, of drugs that deplete the brain of biogenic amines were reviewed. The behavioral changes associated with reserpine administration were interpreted as being primarily a psychomotor retardation-sedation syndrome, due perhaps to a dopamine deficiency, and would not be an adequate model for clinical depression. In susceptible persons, particularly those with a prior history of depression, this psychomotor retardation-sedation might be sufficient to trigger a depression-like episode. More selective amine depletion, produced either by alpha-methyl-paratyrosine or by parachlorophenylalanine is not associated with depression. Yet, these drugs produce a more consistent and greater reduction in amine metabolite concentrations than that reported to occur in depressed patients. In light of this, it is suggested that the depletion of brain norepinephrine and dopamine, or serotonin, is, in itself, not sufficient to account for clinical depression.