The lessons of platelet monoamine oxidase

The lessons of platelet monoamine oxidase 1 Over a decade has elapsed since the first report by Murphy & Wyatt (1972) that platelet monoamine oxidase (MAO) is reduced in chronic schizophrenic patients.The finding was exciting because it seemed to herald a new, more scientific level of research on the biological aspects of schizophrenia.Previous claims in schizophrenia of altered serum factors (Heath et al. 1958), of elevated serum creatinine phosphokinase (Meltzer, 1968), or of abnormal urinary metabolites (Friedhoff& Van Winkle, 1962) had never been entirely proven or disproven.However, such findings tended to be isolated from comprehensive theories of schizophrenia and unrelated to neuroleptic treatment, the major effective biological treatment of schizophrenia.Reduced MAO seemed logically to be an aetiological factor in schizophrenia, for MAO metabolizes dopamine, and MAO deficiency would predispose to dopamine excess.Dopamine excess had been proposed as a pathophysiological basis for the overt symptoms of schizophrenia (Carlsson et al. 1972), and neuroleptics had been shown to act as dopamine receptor blockers (Snyder et al. 1970).MAO is an enzyme, and biological theory in 1972 was much preoccupied with the 'central dogma' that genes express themselves by determining the amino acid sequence of particular proteins that are the products of the gene (Watson, 1965).Rosenthal et al. (1971) had just published their influential adoption studies of schizophrenia that helped to reverse the highly sceptical attitudes of North American psychiatrists towards the issues created by the methodological difficulties associated with previous genetic studies in the field of schizophrenia.Low platelet MAO in schizophrenia was therefore viewed as the possibly enzymatic expression of the genetic predisposition to schizophrenia.It was an admission ticket for psychiatric research to the great arena of molecular genetics, the forefront of modern biology.Moreover, it seemed possible to create a molecular biology of schizophrenia without sacrificing psychiatry's legacy of biological-psychological interactions.Low MAO could only represent the genetic predisposition to schizophrenia.Under usual conditions MAO is present in great excess and a relative deficiency would not affect dopamine metabolism (Murphy & Kalin, 1980).Other, presumably environmental, causes would be necessary to stimulate a dopamine release that might become a pathological dopamine excess' psychosis' in an individual with low MAO.Neuroleptic or dopamine receptor blocking drugs could be seen to reduce the effects of dopamine excess and thereby ameliorate schizophrenic symptoms, while leaving unaffected the low platelet MAO and the genetic predisposition to further attacks (Wyatt et al. 1975).In the early 1970s the implications of the finding of low platelet MAO in schizophrenia were exciting indeed to young psychiatric research workers at the National Institute of Mental Health, the author of this editorial among them.The heuristic result was an explosion of empirical studies.Nies et al. (1973) had already shown, in a comparison of normal monozygotic and dizygotic twins, that interindividual differences in platelet MAO are under a high degree of genetic control, with a heritability of over 80%.Preliminary studies showed no effect of neuroleptic drug treatment on platelet MAO activity (Murphy et al. 1975).Yet it was, of course, possible that other factors such as hospital diet, stress, infection or inactivity could be artefactual causes of low platelet MAO in schizophrenia.It seemed an impossible task to eliminate each of these factors one by one.Basing himself on a strategy used extensively by Pollin (Pollin & Stabenau, 1968), Wyatt planned a study of monozygotic twins discordant for schizophrenia (Wyatt et al. 1974).Such twins are discordant for neuroleptic treatment history, for hospitalization effects, and for effects of stresses secondary