The Sahlgrenska Academy at Göteborg University, Institute of Clinical Neuroscience, 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 23 November 2001; in revised form 10 April 2002; accepted 2 May 2002
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ABSTRACT |
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INTRODUCTION |
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SUBJECTS AND METHODS |
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Study design
Subjects, none of whom had a history of treatment as inpatients for alcohol-related problems, were examined physically and psychiatrically using a semi-structured interview by a psychiatrist at an alcoholism treatment unit of the University Hospital. They were assessed for alcohol-misuse/dependence according to DSM-IV criteria (American Psychiatric Association, 1994). Those who fulfilled criteria for alcohol dependence were thereafter assessed for type 1 alcoholism, using the criteria of von Knorring et al. (1985): subjective alcohol problems should have started after the age of 25 years and the first treatment contact should have been established after the age of 30 years. If alcohol problems had started earlier, no signs of social complications such as violence while intoxicated, absence from work due to alcohol, loss of job, legal difficulties (e.g. arrest for intoxication, traffic accidents while intoxicated), arguments or difficulties with family or friends because of excessive alcohol misuse were to be present.
Daily alcohol consumption during the 2 weeks prior to blood sampling was registered using alco-cards (Balldin et al., 1994), Time Line Follow Back (Sobell et al., 1980
) or daily telephone calls (Eriksson et al., 2001
). Blood samples were collected the day after the end of alcohol intake for determination of platelet MAO-B activity and liver function parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
-glutamyltransferase (GGT); upper laboratory limit for all liver enzymes: 0.8 µkat/l]. Determination of narcotic drugs (including benzodiazepines) in urine samples was also performed using suitable laboratory screening procedures. Patients smoking/snuffing status was recorded. Their family histories of alcoholism in first-degree relatives were also recorded. Subjects who reported at least one alcohol-dependent first-degree relative (parents or siblings) were classified as FHP and those who reported none as FHN alcohol-dependent subjects.
Biochemical analyses
Platelets were isolated from EDTA-blood as previously described (Svennerholm et al., 1982). The cell homogenate used as enzyme source in the assay of MAO-B was prepared by sonication in ice-chilled water for 60 s. The protein content of the homogenate was determined by the bicinchoninic acid procedure (Smith et al., 1985
). The enzyme activity was assayed radiochemically with ß-phenylethylamine as substrate with a concentration of 5.0 µM in the final assay (Fowler and Tipton, 1981
). The specific enzyme activity is expressed as µkat/kg cell protein. The intra-assay variation was 46%, calculated on assayed duplicates of different samples. For determination of the inter-assay precision, a pool of platelets was aliquoted and stored at 80°C. Fresh aliquots were assayed on seven different occasions during a 5-month period. The inter-assay variation of the pooled platelet samples was 10%.
Statistical analyses
Between-group comparisons were performed using Students t-test (Stat-View, Abacus). Data are presented as the means ± SD.
The study was approved by the Ethics Committee of Göteborg University, Sweden. Informed consent was obtained from all subjects. Subjects were not paid for their participation in the study.
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RESULTS |
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From the entire sample of 76 male alcohol-dependent subjects, 57% were FHP, i.e. reported that they had at least one alcohol-dependent first-degree relative. Fifty per cent of the total sample reported that they had one or two and 7% reported that they had three or four alcohol-dependent first-degree relatives.
Thirty-four per cent (n = 26) of the total sample were current smokers and 14% (n = 11) current snuffers. There was no difference in the proportion of smokers and snuffers between the FHP and FHN alcohol-dependent subjects. Furthermore, there was no difference in the number of cigarettes smoked per day between smokers in the FHP and FHN groups.
Platelet MAO-B activity did not differ between FHP and FHN alcohol-dependent subjects (4.8 ± 1.6 and 4.9 ± 1.5 µkat/kg protein, respectively). However, as seen in Fig. 1, the alcohol-dependent subjects reporting three or four alcohol-dependent first-degree relatives (n = 5) had significantly lower platelet MAO-B activity than the remaining FHP alcohol-dependent subjects (n = 38; P < 0.02) or the FHN alcohol-dependent subjects (n = 33; P < 0.02). Furthermore, the lowest and third lowest values of platelet MAO-B activity levels were found in the group of FHP subjects reporting three or four alcohol-dependent first-degree relatives.
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When analysing platelet MAO-B activity for smokers alone in the three subgroups, the alcohol-dependent subjects reporting three or four alcohol-dependent first-degree relatives had significantly lower platelet MAO-B activity (n = 4; 3.4 ± 1.3 µkat/kg protein) in comparison to FHN alcohol-dependent subjects (n = 8; 4.9 ± 1.1 µkat/kg protein; P < 0.05), but not in comparison to those with one or two first-degree relatives (n = 14; 4.4 ± 1.2 µkat/kg protein).
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DISCUSSION |
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Platelet MAO-B activity did not differ between FHP and FHN alcohol-dependent subjects. Since current smoking has been reported to reduce platelet MAO-B activity (Anthenelli et al., 1998; Whitfield et al., 2000
; M. Eriksson et al., unpublished data) the finding that current smokers were equally distributed between the FHP and FHN alcohol-dependent subjects is important, making it unlikely that the effects of smoking had influenced the results. Furthermore, when the current smokers were excluded from the groups of FHP and FHN alcohol-dependent subjects, there was still no difference in platelet MAO-B activity between FHP and FHN alcohol-dependent subjects. Finally, in the present study, smokers did not have lower platelet MAO-B activity than non-nicotine users, in contrast with the findings of other studies (see above). The effect of smoking on platelet MAO-B activity is rather modest, about a 20% reduction (Anthenelli et al., 1998
; M. Eriksson et al., unpublished data) and it may therefore be that the number of subjects in the present study was too small to detect this modest difference.
The finding of no difference in platelet MAO-B activity between FHP and FHN alcohol-dependent subjects is in agreement with the results from the studies of Soyka et al. (2000) and Whitfield et al. (2000). It is, however, in disagreement with several earlier studies reporting lower platelet MAO-B activity in FHP, in comparison to FHN alcohol-dependent subjects (Major and Murphy, 1978; Sullivan et al., 1979
; Alexopoulos et al., 1983
; Rommelspacher et al., 1994
). It should be noted that in these latter studies, the smoking status of subjects was not reported. The possibility therefore cannot be excluded that the lower platelet MAO-B activity in the FHP alcohol-dependent subjects might have been due to an over-representation of current smokers in this group of subjects. Thus, it should be noted that, in the present study, in accordance with the findings of Whitfield et al. (2000) no difference was observed in platelet MAO-B activity between FHP and FHN alcohol-dependent subjects, even when the effects of smoking were taken into account. Consequently, it appears unlikely that low platelet MAO-B activity is a genetic marker for vulnerability to alcohol dependence. However, it should be noted that the FHP alcohol-dependent subjects in the present study who reported three or four alcohol-dependent first-degree relatives had lower platelet MAO-B activity than the remaining FHP alcohol-dependent subjects (one or two alcohol-dependent first-degree relatives) or the FHN alcohol-dependent subjects. This finding should be interpreted with caution, due to the small number of subjects (n = 5), but it is noteworthy that Pandey et al. (1988) found that alcohol-dependent subjects with low platelet MAO-B activity had a higher frequency of family history for alcoholism, i.e. two or more alcohol-dependent family members. The smoking status of the alcohol-dependent subjects in the study of Pandey et al. (1988) was, however, not registered. Nevertheless, it cannot be excluded that FHP alcohol-dependent subjects with a large number of alcohol-dependent first-degree relatives may have lower platelet MAO-B activity.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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