New Markers of alcohol consumption : Development and evaluation of the clinical use of carbohydrate-deficient transferrin in serum and 5-hydroxytryptophol in urine

Abstract: New Markers of Alcohol Consumption Development and Evaluation of the Clinical Use of Carbohydrate-Deficient Transferrin in Serum and S-Hydroxytryptophol in Urine Dissertation from Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, S-171 76 Stockholm, Sweden Treatment of alcohol dependence and evaluation of treatment and research programs are often based on self-reports of the patients. Since the alcohol consumption pattern does not always relate to the reported behaviour there is a need for validation by reliable biochemical markers. In this study, urinary 5-hydroxytryptophol levels have been shown to increase in a dose dependent way after alcohol intake. Increased levels can be seen several hours after blood ethanol levels reach zero, and the 5-hydroxytryptophol/5-hydroxyindole-3-acetic acid (5-HTOL/5-HIAA) ratio has showed a satisfactory degree of individual stability, when it was followed daily in a group of teetotallers for one month. The distribution of the 5-HTOL/5-HIAA ratio differed statistically between a group of teetotallers and regular consumers. A 5-HTOL/5-HIAA ratio of 20 (pmoles/nmoles) is proposed as a cut-offlimit. Carbohydrate-deficient transferrin (CDT) in serum has been shown to be a specific marker for regular alcohol consumption. Detection of relapse in alcohol consumption in alcohol-dependent patients were examined using CDT and 5-HTOL as validation of self-reports. Clinical ratings and self-reports about alcohol consumption were performed three times a week during six months. The frequency of alcohol consumption as measured by self-reports differed significantly compared to the biochemical markers. None of the alcohol-dependent patients totally abstained when 5-HTOL values were used for detecting alcohol intake. Apart from high CDT values at the start of the treatment only few showed elevated values during treatment due to more sporadic alcohol intake. The reference levels of CDT (20 U/l for males and 27 U/l for females) is used for a normal population. In monitoring alcohol-dependent patients individualized levels, based on the lowest values in each individual were used. By using individualized levels the sensitivity of CDT increased. Most episodes of elevated levels of CDT could be validated clinically and/or by 5-HTOL 14 days preceeding each serum sampling. 5-HTOL and CDT seems to be complemantary markers since they reflect different aspects of alcohol intake with respect to time, quantity, sensitivity, and specificity, and therefore have different properties in treatment monitoring. The utility of CDT and gamma-glutamyl transferase (GGT) as complementory markers of excessive alcohol consumption was examined. CDT appeared to be the most sensitive marker in the out-patient group. In 114 alcoholics sampled at random at a detoxification unit there was a higher degree of elevated GGT levels, but no significant correlation between CDT and GGT. Hence, measurement of both CDT and GGT may increase the possibility to identify excessive alcohol consumption. By following changes in CDT and GGT values during a period of treatment monitoring after withdrawal, the most useful individual marker can be determined. Finally, the effects of long-term abstinence on psychological functioning in alcohol-dependent patients and healthy controls were compared through a prospective longitudinal study design. For the alcohol- dependent patients the self-reports were compared with biochemical markers. Patients and controls differed in terms of mood stability, craving, cognitive, and vegetative disturbances. A gradual normalization back to baseline levels was observed for some symptoms. The unstable affective state for alcohol-dependent patients may be related to the protracted withdrawal or may represent residual symptomatology. Among the alcohol-dependent patients differences in overall psychological functioning and craving for alcohol were found in relation to low- or high-frequency alcohol intake during long-term treatment. The findings have important implications in that reliable identification of patients' alcohol consumption pattern using biochemical markers would allow for an individually treatment. Key Words: Alcohol drinking, 5-hydrogxytryptophol, 5-hydroxyindole-3-acetic acid, urine, human, carbohydrate-deficient transferrin, biochemical marker, gamma-glutamyl transferase, alcohol-dependence protracted withdrawal, relapse, craving, psychological functioning