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
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
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).
![]() |
SUBJECTS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The 16 male subjects had a mean ± SD (range) age of 53 ± 8 (4074) years and body weight of 77 ± 10 (5594) 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 (539) years with an estimated daily alcohol consumption of 289 ± 184 (120840) 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.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
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.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
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
).
![]() |
ACKNOWLEDGEMENTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
FOOTNOTES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Alexopoulos, G. S., Lieberman, K. W. and Frances, R. (1983) Platelet MAO activity in alcoholic patients and their first-degree relatives. American Journal of Psychiatry 140, 15011504.[Abstract]
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association, Washington, DC.
Anthenelli, R. M., Tipp, J., Li, T.-K., Magnes, L., Schuckit, M. A., Rice, J., Daw, W. and Nurnberger, J. I. (1998) Platelet monoamine oxidase activity in subgroups of alcoholics and controls: results from the collaborative study on the genetics of alcoholism. Alcoholism: Clinical and Experimental Research 22, 598604.[ISI][Medline]
Bench, C. J., Price, G. W., Lammertsmaa, A. A., Cremer, J. C., Luthra, S. K., Turton, D., Dolan, R. J., Kettler, R., Dingemanse, J., Da Prada, M., Biziere, K., McClelland, G. R., Jamieson, V. L., Wood, N. D. and Frackowiak R. S. J. (1991) Measurement of human cerebral monoamine oxidase type B (MAO-B) activity with positron emission tomography (PET): a dose ranging study with the reversible inhibitor Ro 19-6327. European Journal of Clinical Pharmacology 40, 169173.[ISI][Medline]
Berggren, U., Fahlke, C. and Balldin, J. (2000) Transient increase in platelet monoamine oxidase B activity during early abstinence in alcoholics: implications for research. Alcohol and Alcoholism 35, 377380.
Cloninger, C. R., Sigvardsson, S. and Bohman, M. (1996) Type I and II alcoholism: an update. Alcohol Health Research World 20, 1823.
Devor, E. J., Cloninger, C. R., Hoffman, P. L. and Tabakoff, B. (1993) Association of monoamine oxidase (MAO) activity with alcoholism and alcoholic subtypes. American Journal of Medical Genetics 48, 209213.[ISI][Medline]
Faraj, B. A., Lenton, J. D., Kutner, M., Camp, V. M., Stammers, T. W., Lee, S. R., Lolies, P. A. and Chandora, D. (1987) Prevalence of low monoamine oxidase function in alcoholism. Alcoholism: Clinical and Experimental Research 11, 464467.[ISI][Medline]
Farren, C. K., Clare, A. W., Tipton, K. F. and Dinan, T. G. (1998) Platelet MAO activity in subtypes of alcoholics and controls in a homogenous population. Journal of Psychiatric Research 32, 4954.[ISI][Medline]
Fowler, C. J., Ekstedt, B., Egashira, T., Kinemuchi, H. and Oreland, L. (1979) The interaction between human platelet monoamine oxidase, its monoamine substrates and oxygen. Biochemical Pharmacology 15, 30633068.
Glassman, A. H. and Koob, G. F. (1996) Psychoactive smoke. Nature 379, 677678.[ISI][Medline]
Hallman, J., von Knorring, L. and Oreland, L. (1996) Personality disorders according to DSM-III-R and thrombocyte monoamine oxidase activity in type 1 and type 2 alcoholics. Journal of Studies on Alcohol 57, 155161.[ISI][Medline]
Major, L. F. and Murphy, D. L. (1978) Platelet and plasma amine oxidase activity in alcoholic individuals. British Journal of Psychiatry 132, 548554.[Abstract]
Major, L. F., Goyer, P. F. and Murphy, D. L. (1981) Changes in platelet monoamine oxidase activity during abstinence. Journal of Studies on Alcohol 42, 10521057.[ISI][Medline]
Oreland, L., Garpenstrand, K., Damberg, M., Alm, P. O., Thorell, L.-H., af Klinteberg, B. and Ekblom, J. (1999) The correlation between platelet MAO activity and personality the effect of smoking and possible mechanisms behind the correlation. Neurobiology 7, 191203.[Medline]
Pandey, G. N., Fawcett, J., Gibbons, R., Clark, D. C. and Davis, J. M. (1988) Platelet monoamine oxidase in alcoholism. Biological Psychiatry 24, 1524.[ISI][Medline]
Parsian, A., Suarez, B. K., Tabakoff, B., Hoffman, P., Ovchinnikova, L., Fisher, L. and Cloninger, C. R. (1995) Monoamine oxidases and alcoholism. I. Studies in unrelated alcoholics and normal controls. American Journal of Medical Genetics 60, 405416.
Rommelspacher, H., May, T., Dufeu, P. and Schmidt, L. G. (1994) Longitudinal observations of monoamine oxidase B in alcoholics: differentiation of marker characteristics. Alcoholism: Clinical and Experimental Research 18, 13221329.[ISI][Medline]
Soyka, M., Bondy, B., Benda, E., Preuss, U., Hegerl, U. and Möller, H. (2000) Platelet monoamine oxidase activity in alcoholics with and without a family history of alcoholism. European Journal of Addiction Research 6, 5763.
Sullivan, J. L., Stanfield, C. N., Schanberg, S. and Cavenar, J. (1978) Platelet monoamine oxidase and serum dopamine-beta-hydroxylase activity in chronic alcoholics. Archives of General Psychiatry 35, 12091212.[Abstract]
Sullivan, J. L., Cavenar, J., Maltbie, A. A., Lister, P. and Zung, W. W. (1979) Familial biochemical and clinical correlates of alcoholics with low platelet monoamine oxidase activity. Biological Psychiatry 14, 385394[ISI][Medline]
Sullivan, J. L., Baenziger, J. C., Wagner, D. L., Rauscher, F. P., Nurnberger, J. I., Jr and Holmes, J. S. (1990) Platelet MAO in subtypes of alcoholism. Biological Psychiatry 27, 911922.[ISI][Medline]
Tabakoff, B., Hoffman, P. L., Lee, J. M., Saito, T., Willard, B. and De Leon-Jones, F. (1988) Differences in platelet enzyme activity between alcoholics and nonalcoholics. New England Journal of Medicine 318, 134139.[Abstract]
von Knorring, L. and Oreland, L. (1996) Platelet MAO activity in type 1/type 2 alcoholics. Alcoholism: Clinical and Experimental Research 20, 224A230A.[Medline]
von Knorring, L., Oreland, L. and Winblad, B. (1984) Personality traits related to monoamine oxidase activity in platelets. Psychiatry Research 12, 1126.[ISI][Medline]
Whitfield, J. B., Pang, D., Bucholz, K. K., Madden, P. A., Heath, A. C., Statham, D. J., Martin, N. G. (2000) Monoamine oxidase: associations with alcohol dependence, smoking and other measures of psychopathology. Psychological Medicine 30, 443454.[ISI][Medline]
Wiberg, A., Gottfries, C. G. and Oreland, L. (1977) Low platelet monoamine oxidase activity in human alcoholics. Medical Biology 55, 181186.[ISI][Medline]