Deficient production of tyramine and octopamine in cases of depression

Abstract

THE cause or causes of depressive illness are unknown, although biochemical evidence points to a physical basis for the psychiatric and somatic features of the disease¹. For nearly 20 years, the amine hypothesis² has been the most favoured explanation and putative derangements of noradrenaline and/or 5-hydroxytryptamine economy have been invoked as the systems of primary disturbance. Careful scrutiny, however, has revealed major inconsistencies in this hypothesis³. Some of the strongest evidence in its favour has been the ability of tricyclic antidepressant drugs to act as potent monoamine uptake inhibitors, thus potentially facilitating neurotransmission at the synaptic cleft; but recently, two drugs in this group, iprindole and mianserin, have been shown to be devoid of both noradrenaline and 5-hydroxytryptamine re-uptake-inhibiting ability, although each is a clinically effective antidepressant (for review see ref. 4). Two things should be pointed out in this connection. First, most pharmacological experiments performed to test the hypothesis have focused on noradrenaline and 5-hydroxytryptamine, whilst a possible role for the so-called trace amines⁵ has been almost completely neglected. And second, the direct clinical approach based on the detection of possible metabolic abnormalities has resulted in conflicting and controversial data³. We now report preliminary evidence pointing to a deficient production of two trace amines, tyramine and octopamine, in patients with depressive illness.