Prevalence of Low Monoamine Oxidase Function in Alcoholism

Abstract

Several studies have found a trend for low platelet monoamine oxidase activity (MAO) in alcoholism but with a great deal of overlap in MAO activity of alcoholics versus controls. The main objective of this study was to carry out a detailed assessment of MAO function that included the measurement of key kinetic parameters (i.e., Km, Vmax) in three groups of male subjects: (a) 51 hospitalized chronic alcoholics, (b) 16 recovering alcoholics with 2-10 years of abstinence, and (c) 21 controls. MAO activity was assayed radiochemically with [14C]tyramine as substrate (43-729 microM). The present study demonstrated that alcoholics had low platelet MAO activity (p less than 0.05). Kinetic analysis revealed a substantial reduction (p less than 0.01) in enzyme Vmax values of chronic and recovering alcoholics. Greater than 95% of the alcoholics had Vmax values lower than the smallest value of control subjects. Moreover, 100% of the alcoholics in both groups exhibited exceedingly low Vmax values that were below the 25th percentile of controls. In summary, results of MAO Vmax determinations provided us with a better separation of the alcoholics from controls. Measurements of platelet MAO function that include enzyme Vmax may provide us a reliable biochemical marker for alcoholism.

Detoxified alcoholics, major depressives and tyramine sulphate excretion

“…Where this happens, however, it may reflect on the status of the marker as an epiphenomenon, mediated by a peripheral biological change which occurs in both conditions, perhaps for very different reasons. Examples are the thyrotropin-stimulating hormone response to thyrotropinreleasing hormone, present in about a third of major depressives (Loosen and Prange, 1982), a small number of their first degree relatives (Brambilla et al, 1980) and in about the same proportion in alcoholic patients and their sons (Radouco-Thomas et al, 1984); low Bmax of [3H]imipramine binding (Suranyi-Cadotte et al, 1989); blunted growth hormone response to clonidine (Matussek et al, 1980); low platelet monoamine oxidase (MAO) activity towards tyramine, proposed as a trait marker for alcoholism by Faraj et al (1987), in this case similar to bipolar depression but not to unipolar patients who show high platelet MAO activity (Gudeman et al, 1982); low concentrations of cerebrospinal fluid (CSF) GABA (Berrettini and Post, 1984) and perhaps of 5-hydroxyindolacetic acid (Melzer and Lowy, 1987); and CSF HVA concentrations (Roy et al, 1991 ).…”

Changes in brain MAO activity and glycogen levels upon chronic alcoholization of three successive generations of rats

“…However, whereas 2nd and 3rd generation alcoholized rats tended to return toward control conditions with respect to brain and body weights and the braidbody weight ratio (and who qualitatively appeared to be much healthier than the rats of the 1st alcoholized generation), it is evident from the other data (MA0 activities and cerebral glycogen content) that there was a far greater neurobiological disruption in these rats than in the first generation alcoholized rats. Observations as to the inhibitory effects of ethanol on M A 0 activity were made as early as the 1960's (Maynard and Schenker, 1962;Towne, 1964), and this became a topic of interest for many years to follow (Feldstein et al, 1964;Schenker et al, 1967;Palaic et al, 1971;Carlsson et aI, 1980;Tabakoff et al, 1985;Faraj et al, 1987;Kolomeets and Uzbekov, 1991;Gorkin et al, 1992;Kono et al, 1993).…”

“…Although a certain number of the results obtained to date remain ambiguous, several reports mentioned differences between control and either ethanol-intoxicated or ethanol-preferring animals, in the noradrenergic (Kiianmaa et al, 1975;Penn et al, 1978;Rossetti et al, 1992), dopaminergic (Myers and Melchior, 1975;Fadda et al, 1980;Rommelspacher et al, 1992) and serotonergic (Myers et al, 1972;Murphy et al, 1982;for review, see Sellers et al, 1992) systems. Particular attention has been paid to the main enzymatic pathway responsible for the degradation of these neurotransmitters, that catalyzed by the enzyme monoamine oxidase (MAO,EC 1.4.3.4; amine:oxygen oxidoreductase (deaminating, flavin-containing)), (Carlsson et al, 1980;Tabakoff et a1, 1985;Faraj et al, 1987).…”

Biological markers of alcoholism

“…The third category of markers are those which are indicators of psychological attributes or psychiatric states. The one which has been most thorougly investigated is platelet monoamine oxidase activity (MAO), which has been shown in many papers [35][36][37][38] to be lower in alcoholics than controls. This seems to be a trait marker, because the low values can persist over a considerable period of abstinence from alcohol E39,4o].…”