Institute of Clinical Neuroscience, Department of Psychiatry and Neurochemistry, Sahlgren University Hospital/Mölndal, Göteborg University, SE-431 80 Mölndal and
1 Department of Psychology, Göteborg University, P.O. Box 500, SE-405 30 Göteborg, Sweden
Received 29 November 1999; in revised form 8 March 2000; accepted 27 March 2000
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ABSTRACT |
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INTRODUCTION |
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In some earlier studies, it has been shown that smokers also have low platelet MAO-B activity (for review see Oreland et al., 1999). In a recent study by Anthenelli et al. (1998), it was thus suggested that low platelet MAO-B activity is a state marker for cigarette smoking, rather than a trait marker for alcoholism or its subgroups. In a review on trait markers for alcoholism and their clinical utility by Farren and Tipton (1999), the authors discussed platelet MAO-B activity and alcoholism and concluded that Probably the biggest problem has been the failure to address the potential confounder of cigarette smoking ... (Farren and Tipton, 1999, p. 652). However, they further concluded that Despite this, it is difficult to ignore the literature suggesting an association between alcoholism and lowered platelet MAO-B activity. It is quite probable that some association does exist, but the nature of that association is not clear (Farren and Tipton, 1999, p. 652).
Consequently, the relationship between platelet MAO-B activity and alcoholism needs to be further investigated. From a methodological point of view, it appears that the length of the abstinence period is of particular importance. Platelet MAO-B activities have been reported to change during the early abstinence period and may be transiently increased during this time period (Wiberg et al., 1977; Alexopoulos et al., 1981
; Major et al., 1981
). Values for platelet MAO-B activity obtained during this period may therefore be falsely high and a difference in comparison to controls could not thus be obtained. Since the optimal time points for blood samplings have not been precisely defined, the aim of the present study was to investigate repeatedly platelet MAO-B activity in alcohol-dependent subjects for a period of 2 months after the end of alcohol intake. The patients were carefully controlled for sobriety during this time period. Values for platelet MAO-B activity were compared with that of a control group at each time point.
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METHODS |
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Thirteen male patients with a diagnosis of alcohol dependence according to DSM-IV (American Psychiatric Association, 1994) were included in the study. Background data, including smoking status for the patients, are shown in Table 1
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Analysis of platelet MAO-B activity
Platelet-enriched plasma was obtained by centrifugation at 400 g for 10 min. The platelets were isolated by centrifugation at 2250 g for 15 min, then washed with saline and stored as a pellet at 70°C until analysis. MAO-B activity was determined according to Fowler et al. (1979) with ß-phenylethylamine as substrate. The substrate concentration was 12 µmol in a 0.013 mol/l phosphate buffer, pH 7.8, containing 0.03% (w/v) delipidized bovine serum albumin.
Statistics
All statistical calculations were performed using the statistical program Stat View (Abacus). Within-group (alcohol-dependent subjects) comparisons were performed with a paired t-test and between-group (alcohol-dependent subjects vs controls) comparisons with an unpaired t-test. In all tests, two-tailed levels of significance was used. The data are presented as means ± standard deviations (SD).
The study was approved by the Ethics Committee of the Göteborg University, Sweden and informed consent was obtained from all subjects.
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RESULTS |
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DISCUSSION |
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The reason for the transitory increase in platelet MAO-B activity during early abstinence in alcoholics is not known with certainty. This increased activity after cessation of drinking has, however, been suggested to be due to either a temporary increase in the release of catecholamines in the blood, which occurs during the acute alcohol-withdrawal phase, or increased formation and release of newer platelets, containing higher levels of MAO-B activity (Wiberg et al., 1977; Alexopoulos et al., 1981
; Major et al., 1981
).
When comparing the values for platelet MAO-B activity at each time point during the 2 months of abstinence with those of a control group, we found that the patients had significantly lower platelet MAO-B activity at week 1 and at week 8 after cessation of alcohol intake. During the transient increase in platelet MAO-B activity from week 2 to week 6 the values were, on the other hand, not different from those of the control group. This latter finding clearly demonstrates that the transient increase in platelet MAO-B activity during early abstinence in alcohol-dependent patients may conceal a difference from a control group. Among studies that have found no difference in platelet MAO-B activity between alcoholics and controls, it is noteworthy that in the study by Tabakoff et al. (1988), the alcoholics had been abstinent for a mean period of 3 weeks. It is thus possible that a transient increase in platelet MAO-B activity, which occurs at this time point, may have concealed a difference from the control group, a possibility also discussed by the authors (Tabakoff et al., 1988). Regarding the study of Parsian et al. (1995), it is noted that the time points for determination of platelet MAO-B activity were recorded in only a subgroup of the subjects and the authors therefore concluded that the importance of the role of abstinence is difficult to evaluate in their study. In the multicentre investigation by Anthenelli et al. (1998), one factor that probably contributed to the results was, as also suggested by the authors, the inter-site differences where blood samples were collected at various lengths of abstinence from alcohol. On the other hand, in the study of Farren et al. (1998), the possibility of a transient increase in platelet MAO-B activity after the end of alcohol intake was carefully taken into consideration and thoroughly discussed. In that study, the alcoholics had been abstinent for an average time of about 4 months (16.7 weeks), which is a time point at which no transient changes in platelet MAO-B activity is expected (Farren et al., 1998
).
Taken together, we found in this study that platelet MAO-B activity was transiently increased in alcohol-dependent patients from 2 to 6 weeks after the end of a period of heavy alcohol intake. During this period, the platelet MAO-B activity levels were not different from that of a control group. In this study, platelet MAO-B activities were, however, lower immediately after the end of the drinking period and also after 2 months of abstinence, compared to controls. This clearly demonstrates the necessity to use defined time points for collection of blood in an investigation of platelet MAO-B activity in alcoholism. The transient increase in platelet MAO-B activity in alcohol abstinence may conceal a difference from a control group. We thus suggest that the preferential time point for obtaining values for platelet MAO-B activity should be 2 months after the end of alcohol intake or, as mentioned earlier, immediately after the end of the drinking period.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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REFERENCES |
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