PLATELET MONOAMINE OXIDASE B IN FAMILY HISTORY POSITIVE AND FAMILY HISTORY NEGATIVE TYPE 1 ALCOHOL-DEPENDENT SUBJECTS

Ulf Berggren, Matts Eriksson, Claudia Fahlke1,*, Kaj Blennow and Jan Balldin

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


    ABSTRACT
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Aims and methods: In the present study platelet monoamine oxidase B (MAO-B) activity was investigated in 76 male type 1 alcohol-dependent subjects with and without a family history of alcoholism. Results: Platelet MAO-B activity did not differ between family history positive (FHP) and family history negative alcohol-dependent subjects. The smoking status of the subjects was registered and there was still no difference between the groups when possible effects of smoking were taken into account. It should, however, be noted that platelet MAO-B activity was lower in alcohol-dependent subjects with three or four alcohol-dependent first-degree relatives. Conclusions: Although this latter finding should be interpreted with caution due to the small number of subjects, 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.


    INTRODUCTION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Platelet monoamine oxidase B (MAO-B) activity has been investigated in numerous studies of alcohol-dependent subjects, but the findings have been contradictory. However, in several studies low platelet MAO-B activity has been found and therefore proposed to be a trait marker for alcohol dependence, especially of type 2 alcoholism, which is associated with personality traits, such as impulsiveness, monotony avoidance and sensation-seeking behaviour (Wiberg et al., 1977Go; Major and Murphy, 1978Go; Sullivan et al., 1978Go, 1990Go; von Knorring et al., 1984Go; Faraj et al., 1987Go; Pandey et al., 1988Go; Devor et al., 1993Go; Rommelspacher et al., 1994Go; Hallman et al., 1996Go; von Knorring and Oreland, 1996Go). Conversely, in several other studies, of which some included type 2 alcoholics, no such association has been observed (Tabakoff et al., 1988Go; Parsian et al., 1995Go; Anthenelli et al., 1998Go; Farren et al., 1998Go; Soyka et al., 2000Go; Whitfield et al., 2000Go). In two of these studies (Anthenelli et al., 1998Go; Whitfield et al., 2000Go) it was found that current smoking reduced platelet MAO-B activity and it was therefore suggested that low platelet MAO-B activity is a state marker for cigarette smoking, rather than a trait marker for alcohol dependence or for its subtypes. In this context, it should be noted that smoking not only has a peripheral effect on MAO-B activity in platelets, but also inhibits MAO-B activity in the brain (Fowler et al., 1996Go). Nevertheless, in most of the studies in which family history of alcoholism was taken into account, family history positive (FHP) alcohol-dependent subjects have been reported to have lower platelet MAO-B activity than family history negative (FHN) alcohol-dependent subjects (Major and Murphy, 1978Go; Sullivan et al., 1979Go; Alexopoulos et al., 1983Go; Rommelspacher et al., 1994Go), although Soyka et al. (2000) reported no difference. In addition, Alexopoulos et al. (1983) found that first-degree relatives of alcohol-dependent subjects who did not fulfil criteria for alcohol dependence had lower platelet MAO-B activity. Thus, low platelet MAO-B activity may be a genetic marker for vulnerability to alcohol dependence. However, it is noteworthy that in the study of Whitfield et al. (2000) FHP alcohol-dependent subjects did not have lower platelet MAO-B activity when the effects of smoking were taken into account. Furthermore, in a recent study of ours (Berggren et al., 2002Go) carried out on a relatively small number of long-term abstinent FHP and FHN type 1 alcohol-dependent subjects, an unexpected higher level of platelet MAO-B activity in the FHP subjects, due to an over-representation of current smokers, which thereby lowered platelet MAO-B activity, was detected in the FHN subjects. It is therefore of importance that the effects of smoking on platelet MAO-B activity be taken into account when platelet MAO-B activity is compared between FHP and FHN alcohol-dependent subjects. Thus, the aim of the present study was to examine platelet MAO-B activity in FHP and FHN alcohol-dependent subjects in whom smoking status was registered.


    SUBJECTS AND METHODS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Subjects
Male subjects aged 20–65 years were recruited by advertisement in a local daily newspaper. They had to be socially stable, i.e. employed or living on a pension and with a permanent place of residence. They also had to be free of physical or psychiatric disorder not associated with alcohol intake. Furthermore, subjects were not to have received diagnoses of misuse or dependence of substances other than alcohol and nicotine. Their weekly alcohol consumption was >300 g of pure alcohol.

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, 1994Go). 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., 1994Go), Time Line Follow Back (Sobell et al., 1980Go) or daily telephone calls (Eriksson et al., 2001Go). 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 {gamma}-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. Patient’s 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., 1982Go). 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., 1985Go). 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, 1981Go). The specific enzyme activity is expressed as µkat/kg cell protein. The intra-assay variation was 4–6%, 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 Student’s 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.


    RESULTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
The mean ± SD age of the subjects was 51 ± 6 years. Their daily alcohol consumption during the 2 weeks prior to blood sampling was 96 ± 45 g pure alcohol. The values of the liver function parameters AST, ALT and GGT were 0.5 ± 0.3, 0.7 ± 0.5 and 1.4 ± 1.5 µkat/l, respectively.

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. 1Go, 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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Fig. 1. Platelet monoamine oxidase B (MAO-B) activity in type 1 alcohol-dependent subjects with and without family history of alcohol dependence. Subjects without (FHN), or those with (FHP), a family history of alcohol dependence were studied. The middle panel represents individuals with one or two first-degree relatives and the right panel those with three or four first-degree relatives. Data are presented as the means ± SD. **P < 0.02 (Student’s t-test).

 
No difference was observed in platelet MAO-B activity in the smokers (n = 26) when compared to non-nicotine users (n = 39) throughout the entire sample. Neither was there any difference between snuffers (n = 11) and non-nicotine users. There was no difference in platelet MAO-B activity between FHP and FHN alcohol-dependent subjects when smokers were excluded from both groups.

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).


    DISCUSSION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
In the present study of 76 male type 1 alcohol-dependent subjects, 57% reported that they had at least one alcohol-dependent first-degree relative, i.e. were FHP alcohol-dependent subjects. This frequency of positive family history for alcoholism is within the range of 47–57% that has been reported in earlier studies for alcohol-dependent subjects recruited from in-patient samples (Alexopoulos et al., 1983Go; Soyka et al., 2000Go). The frequency of current smokers in the present study was 34% and smokers were equally distributed between FHP and FHN alcohol-dependent subjects.

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., 1998Go; Whitfield et al., 2000Go; 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., 1998Go; 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, 1978Go; Sullivan et al., 1979Go; Alexopoulos et al., 1983Go; Rommelspacher et al., 1994Go). 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.


    ACKNOWLEDGEMENTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
This study was supported by grants from the Swedish Alcohol Monopoly Foundation for Alcohol Research (00/4:2), the Swedish Medical Research Council (K01-21X-13447-02B) and the Swedish Council for Research in Humanities and the Social Sciences (F0416-1999).


    FOOTNOTES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
* Author to whom correspondence should be addressed. Back


    REFERENCES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
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