Transmitter amines in depression

This editorial comments on recent evidence concerning the roles in depression of the transmitter amines 5-hydroxytryptamine (5HT), dopamine (DA) and noradrenaline (NA). It focuses on evidence from brain chemistry and from effects of drugs used in treatment. The literature on urinary excretion of amine metabolites and on platelet erythrocyte and neuroendocrine abnormalities will not be discussed. The transmitter amines account for only a small part of the neuronal population of the brain. Almost all of their cell bodies are in a small part of the brain stem. However, the widespread distribution and prolific arborization of their terminals suggest an importance for 'primitive' aspects of brain function which have been thought to underlie the broad disturbances of behaviour and mood characteristic of the major psychoses. There is an increasing contrast between our knowledge of the complexity of brain transmitter amine systems and the simplicity of the questions with which most research on their significance for the psychoses has so far been concerned. On one hand, largely as a result of animal experiments, we know, or expect, multiple interactions of these transmitters with each other and with numerous other transmitter systems. We suspect that transmitter amines also have non-transmitter roles in the brain (Beaudet & Descarries, 1978; Jones, 1981) and we know of the multiplicity and modifiability of their receptors. Furthermore, it now seems that the long accepted 'one neurone one functioning transmitter' rule is probably incorrect (Hokfelt et al. 1980; Osborne, 1981). If, on the other hand, we turn to the questions asked about amine abnormalities in psychoses, these are still' do they exist?' and, if so, 'do they matter?', i.e. do they have roles in causation or are they secondary to other disturbances which do have causal roles, or to symptoms or to treatments? No amine hypothesis of depression has had a simple history of increasing validation with time, although some difficulties of interpreparation no longer appear as great as they originally did when neurochemical ideas on psychoses mostly depended on a very narrow range of investigations and were based on assumptions such as 'one transmitter defect per gross diagnostic category'. Some recent clarifications of old problems and the emergence of new ones and of new insights into the neurochemistry of depression are commented on below.