Alcohol and Alcoholism Vol. 37, No. 4, pp. 340-343, 2002
© 2002 Medical Council on Alcohol
PLATELET MONOAMINE OXIDASE-B ACTIVITY IN TYPE 1 ALCOHOL-DEPENDENT SUBJECTS IN SUSTAINED FULL REMISSION
The Sahlgrenska Academy at Göteborg University, Institute of Clinical Neuroscience, Psychiatric Section, Sahlgrenska University Hospital/Mölndal, SE-431 80 Mölndal and
1 Department of Psychology, Göteborg University, P. O. Box 500, SE-405 30 Göteborg, Sweden
Received 22 October 2001; accepted 9 January 2002
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ABSTRACT |
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 TOPFOOTNOTES ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
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— Aims: The present study investigated platelet monoamine oxidase-B (MAO-B) activity in male alcohol-dependent subjects in sustained full remission (minimum 1 year), to exclude possible transient changes in platelet MAO-B activity, which occur up to several months after the end of alcohol intake. Methods: MAO-B activity was examined in 16 alcohol-dependent subjects, characterized as type 1 alcoholics, with an abstinence period of 6 ± 7 years (mean ± SD) and in 12 healthy controls. Results: The long-term abstinent alcohol-dependent subjects did not differ from controls in platelet MAO-B activity. Conclusions: Type 1 male alcohol-dependent subjects appear to have normal platelet MAO-B activity. The possibility, however, cannot be excluded that type 2 long-term abstinent alcoholics may have lower platelet MAO-B activity.
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INTRODUCTION |
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TOPFOOTNOTESABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
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Numerous studies have investigated platelet monoamine oxidase (MAO)-B activity in alcohol-dependent subjects. It has been discussed whether platelet MAO-B activity, as a peripheral marker, represents brain MAO-B activity. However, Bench et al. (1991), using positron emission tomography, have shown a close correlation between platelet and brain MAO-B activity. Several studies have demonstrated low platelet MAO-B activity in alcohol-dependent subjects; and this activity is proposed as a trait marker for alcohol-dependence, especially of type 2 alcoholism (Cloninger et al., 1996
), which is associated with personality traits such as impulsiveness, monotony avoidance and sensation-seeking behaviour (Wiberg et al., 1977; Major and Murphy, 1978; Sullivan et al., 1978, 1990; von Knorring et al., 1984; Faraj et al., 1987; Pandey et al., 1988; Devor et al., 1993; Rommelspacher et al., 1994; Hallman et al., 1996; von Knorring and Oreland, 1996). However, several other studies found no such association (Tabakoff et al., 1988; Parsian et al., 1995; Anthenelli et al., 1998; Farren et al., 1998; Soyka et al., 2000; Whitfield et al., 2000), even amongst type 2 alcoholics (Parsian et al., 1995; Anthenelli et al., 1998; Farren et al., 1998). It should, furthermore, be noted that, in two of these studies (Anthenelli et al., 1998; Whitfield et al., 2000), consisting of a large number of subjects, smoking was found to reduce platelet MAO-B activity. It has thus been suggested that low platelet MAO-B activity represents a state marker for cigarette smoking, rather than a trait marker for alcoholism or its subgroups (Anthenelli et al., 1998). Furthermore, Whitfield et al. (2000) concluded that the concept of platelet MAO-B activity being a direct genetic marker of vulnerability to alcohol-dependence cannot be sustained. However, before this appealing conclusion can be accepted, an important methodological issue should be addressed. Platelet MAO-B activity has in several studies been reported to change during the early abstinence period and is transiently increased during this time-period (Wiberg et al., 1977; Alexopoulos et al., 1981; Major et al., 1981; Berggren et al., 2000). Accordingly, values obtained for platelet MAO-B activity during this time-period may differ from those of a control group. In the study by Berggren et al. (2000), platelet MAO-B activity in alcohol-dependent subjects, as compared to controls, was lower during the first week, did not differ during the subsequent 4 weeks and decreased again 2 months after termination of alcohol intake. However, Farren et al. (1998) found no difference in platelet MAO-B activity in alcohol-dependent subjects who had been abstinent for 
4 months, as compared to controls. It cannot therefore be excluded that values for platelet MAO-B activity may fluctuate considerably over a period of several months following termination of alcohol intake.
Therefore, in order to exclude the possibility of transient changes in platelet MAO-B activity during this time-period, we investigated in the present study platelet MAO-B activity in alcohol-dependent subjects who had been abstinent for several years, and compared results obtained with a control group. Furthermore, current smoking was registered in these subjects and platelet MAO-B activity was compared between smokers and non-smokers. Finally, since it has been suggested that further studies are warranted to explore the possible link between MAO activity and family history of alcoholism (Soyka et al., 2000), platelet MAO-B activity in alcohol-dependent subjects with a first- or second-degree alcohol-dependent relative (family history positive; FHP) was compared to activity observed in subjects lacking such relatives (family history negative; FHN).
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SUBJECTS AND METHODS |
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TOPFOOTNOTESABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
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Subjects
This study was performed in an outpatient unit for the treatment of alcoholism and was approved by the Ethics Committee of Göteborg University, Sweden. Informed consent was obtained from all subjects. Sixteen male subjects with a diagnosis of alcohol dependence, in sustained full remission according to DSM-IV (American Psychiatric Association, 1994
), were included in the study. They had a long-standing and frequent contact with the alcoholism treatment unit and were well-known by the staff members. Subjects were physically examined by the investigators and their medical histories and family histories of alcoholism were recorded. Their smoking status was also registered. Blood samples for determination of platelet MAO-B activity and liver function tests (alanine aminotransferase: ALT; aspartate aminotransferase: AST; gamma-glutamyltransferase: GGT) were drawn at this time. The 16 male subjects had a mean ± SD (range) age of 53 ± 8 (40–74) years and body weight of 77 ± 10 (55–94) kg. None reported any somatic or psychiatric disease other than alcohol dependence in sustained full remission, or reported misuse/ dependence on drugs other than alcohol and nicotine. The reported length of their previous period of excessive consumption of alcohol was 16 ± 10 (5–39) years with an estimated daily alcohol consumption of 289 ± 184 (120–840) g pure alcohol. The reported length of period of abstinence prior to investigation ranged from 1 to 20 (7 ± 6) years. The reported past periods of excessive alcohol consumption and current periods of abstinence were confirmed by medical records. No subjects had been treated with psychotropic drugs in the 6 months immediately preceding the investigation.
Twelve male subjects with a mean age ± SD of 46 ± 10 years were recruited as controls. Based on an interview, they were all considered somatically and psychiatrically healthy. Results of routine laboratory analyses, including liver function tests, were all within the laboratory reference ranges. All controls were light social drinkers with a reported weekly alcohol consumption of <100 g pure alcohol.
Analysis of platelet MAO-B activity
Platelet-enriched plasma was obtained 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-phenyl-ethylamine 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.
Statistical evaluation
All statistical calculations were performed using the statistical programme Stat View (Abacus). Between-group comparisons were performed with an unpaired t-test. When analysing correlation between data, univariate Pearson's product-moment correlation was used. In all tests, two-tailed levels of significance were used. The data are presented as means ± SD.
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RESULTS |
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TOPFOOTNOTESABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
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All long-term abstinent alcohol-dependent subjects had values for liver function tests (obtained at the time-point for determination of platelet MAO-B activity) well below the upper reference limits (<0.8 µkat/l). AST was 0.32 ± 0.09 µkat/l (reference range: 0.2–0.8), ALT 0.25 ± 0.3 µkat/l (0.2–0.8) and GGT 0.31 ± 0.14 µkat/l (<0.8).
No correlation was observed between platelet MAO-B activity and age of the subjects, reported length of previous period of excessive alcohol consumption or duration of abstinence. The analyses (Table 1) showed that platelet MAO-B activity did not differ significantly between long-term abstinent alcohol-dependent subjects and controls. When the alcohol-dependent subjects were subgrouped into active smokers (n = 6) and non-smokers (n = 8; ex-smokers or those who had never smoked), the alcohol-dependent subjects who currently smoked revealed a tendency (P = 0.08) towards a lower platelet MAO-B activity in comparison to non-smoker alcohol-dependent subjects. A further tendency (P = 0.08) towards higher platelet MAO-B activity in FHP (n = 7) alcohol-dependent subjects compared to FHN (n = 8) alcohol-dependent subjects was observed.
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DISCUSSION |
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TOPFOOTNOTESABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
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The present study assessed platelet MAO-B activity in alcohol-dependent subjects who had been abstinent for several years. Subjects with such a lengthy abstinence period were selected to exclude the possibility of transient fluctuations in platelet MAO-B activity which may occur several months after termination of alcohol intake (Wiberg et al., 1977
; Alexopoulos et al., 1981; Major et al., 1981; Berggren et al., 2000) and conceal possible differences when compared to control groups. Our results demonstrate that platelet MAO-B activity in alcohol-dependent subjects in long-term abstinence does not differ from that of controls. Thus, having excluded the possibility of transient changes in platelet MAO-B activity subsequent to termination of alcohol intake, no difference in this activity was apparent between alcohol-dependent subjects and controls. This finding is in agreement with results from two recent studies (Anthenelli et al., 1998; Whitfield et al., 2000). However, it should be noted that the majority of alcohol-dependent subjects in long-term abstinence included in the present study commenced alcohol misuse after the age of 25 years and did not exhibit characteristics of type 2 alcoholism (Cloninger et al., 1996) such as antisocial personality traits and complications thought to be consequences thereof. The alcohol-dependent subjects examined in this study could therefore probably be characterized as type 1 alcoholics (Cloninger et al., 1996); accordingly, the findings obtained in the present study do not rule out the possibility that long-term abstinent type 2 alcoholics may indeed have lower platelet MAO-B activity. When alcohol-dependent subjects were subgrouped into smokers or non-smokers, no significant differences were observed in MAO-B platelet activity. However, smokers demonstrated a tendency towards lower platelet MAO-B activity. It is interesting to note that, in the two studies by Anthenelli et al. (1998) and Whitfield et al. (2000), with large numbers of subjects, platelet MAO-B activity was lower among current smokers than non-smokers. On the other hand, it has recently been shown that non-human primates, that exhibit excessive alcohol consumption and type 2-like alcohol features, also have lower platelet MAO-B activity (C. Fahlke et al., in preparation). These results contradict the hypothesis that lower platelet MAO-B activity in type 2 alcoholism is simply an artefact of cigarette smoking, since extraneous variables such as smoking were excluded in the study mentioned.
In this study, FHP alcohol-dependent subjects demonstrated a tendency for higher platelet MAO-B activity, compared to FHN alcohol-dependent subjects. This tendency is at variance with earlier studies reporting either no difference (Soyka et al., 2000) or, as in most studies, lower platelet MAO-B activity in FHP, when compared to FHN alcohol-dependent subjects (Major and Murphy, 1978; Sullivan et al., 1979; Alexopoulos et al., 1983; Rommelspacher et al., 1994). However, on evaluating data obtained in the present study, it was observed that five of the six smokers were included in the FHN group of alcohol-dependent subjects in long-term abstinence. Since smokers tended to have a lower platelet MAO-B activity (see above), this may explain the tendency observed towards a lower platelet MAO-B activity in the FHN group of alcohol-dependent subjects. The latter is corroborated by the finding that FHN alcohol-dependent subjects who were also smokers (n = 5) had significantly lower platelet MAO-B activity compared to non-smoker FHP alcohol-dependent subjects (n = 6; 4.2 ± 0.8 and 6.8 ± 2.6 µkat/kg protein, respectively; P < 0.05).
It is noteworthy that the proportion of smokers is significantly higher in the FHN group of alcohol-dependent subjects, in comparison with the FHP group (P < 0.05; Fisher's exact test). This finding should be interpreted with caution due to the low number of subjects examined, but may nevertheless suggest the presence of two different types of aetiologies for alcohol-dependence in the subjects investigated in this study. Thus, alcohol dependence in 50% of subjects may to some extent have been genetically determined (family histories of alcoholism) whilst in other subjects with no family history of alcoholism smoking may have acted as a ‘gateway drug’ as smoking inhibits MAO, and this could make the use of other drugs, such as alcohol, more likely (Glassman and Koob, 1996). This latter explanation assumes that smoking precedes the development of alcohol dependence although this has not been ascertained in the FHN alcohol-dependent subjects studied here. It should also be noted that the inhibitory effect of smoking on platelet MAO-B activity is probably not due to an inhibitory effect of nicotine, but rather to some other substance(s) of the several thousand components of cigarette smoke (Anthenellli et al., 1998; Oreland et al., 1999).
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ACKNOWLEDGEMENTS |
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TOPFOOTNOTESABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
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This study was supported by grants from the Swedish Alcohol Monopoly Foundation for Alcohol Research (00/4:1), the Swedish Medical Research Council (K01-21X-13447-02B) and the Swedish Council for Research in Humanities and the Social Sciences (F0416-1999).
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FOOTNOTES |
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TOPFOOTNOTESABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
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* Author to whom correspondence should be addressed.
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