Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence?

The serotonin (5-hydroxytryptamine: 5-HT) system has been thought to play an important role in several steps of alcohol craving. A number of studies, including our own, have reported that alcohol dependence is associated with dysfunction of 5-HT transmission. Pharmacological and clinical studies have shown that the 5-HT transporter (5-HTT) and the 5-HT1A receptor appear to be candidate loci for the aetiology of alcohol dependence. We have analysed the presence of different 5-HTT and 5-HT1A variants in 104 alcohol-dependent patients and 38 controls for a possible association with alcohol dependence. In alcohol-dependent patients, we found a high frequency of the S allele of 5-HTTLPR (45.5% vs. 29%, chi2 = 6.33, p = 0.0081). No other significant differences were observed between the two populations for other polymorphisms. These results provide, for the first time, preliminary evidence that alcohol abuse disorders are associated with a genetic variant for 5-HT transmission. It might be possible to use this detection of the "S" allele as a clinical tool for pathology diagnosis and to advise recovering alcoholics and it could represent an aid to the prevention of relapse. Therapeutic actions could be envisaged to use this genotyping to help select the best therapeutic strategy.

Nephelometric determination of carbohydrate deficient transferrin.

We describe a technique for measuring carbohydrate-deficient transferrin (CDT) in serum. Serum transferrin fractions are separated by anion-exchange chromatography on microcolumns. Sialic acid-deficient transferrin fractions are collected in the eluate, and transferrin is then quantified by a rate-nephelometric technique. Imprecision (CV) was 4-5% within-run and 7-9% between runs (n = 15). Comparison with an isoelectric focusing-immunofixation method for transferrin index (x) yielded y = 761x + 7, Sy/x = 39 mg/L. Assay of sera from 90 abstainers or moderate consumers of alcohol showed that 81 (90%) had CDT concentrations between 30 and 70 mg/L. Among 74 alcoholics admitted to an alcohol treatment center, 54 (73%) had CDT > 70 mg/L, i.e., the diagnostic sensitivity was 73% at a specificity of 90% (area under receiver-operator characteristic curve = 0.891).

Plasma lipids and alcohol consumption in alcoholic men: effect of withdrawal.

This study examines the effect of alcohol withdrawal on plasma lipids and particularly on HDL-cholesterol subfractions, in 18 middle-aged, clinically healthy but chronically drinking men, institutionalized for withdrawal therapy. Plasma lipids, total HDL and HDL3-cholesterol, Apo A-I and Apo B were assayed before and after 30-86 days of abstinence. A 38% decrease in mean total HDL-cholesterol levels was observed after withdrawal therapy (P = 0.0002), and this was due mainly to a drop in HDL3-cholesterol concentrations (-43%, P = 0.0002). The decrease in HDL2-cholesterol concentrations was also significant (-21%, P < 0.005) but less marked. These results were not dependent on quantities of alcohol ingested before therapy, on duration of hospitalization and on changes in dietary fat intake or smoking habits. Apo A-I levels decreased (-39%, P = 0.0002) and the magnitude of the decrease after alcohol withdrawal was positively related to the duration of hospitalization. Apo B levels increased (+24%, P < 0.005). Among the anthropometric parameters, arm muscle area was significantly higher after alcohol withdrawal. The energy and macronutrient intakes did not significantly change during hospitalization. It is concluded that the modifications of HDL-cholesterol, HDL3-cholesterol, HDL2-cholesterol Apo A-I and Apo B values were induced by alcohol withdrawal in this population of chronic french alcoholics.

Platelets 3H 5-HT uptake in descendants from alcoholic patients: a potential risk factor for alcohol dependence?

We studied platelet 3H-serotonin uptake in 32 former alcoholics, withdrawn for from 1 month to 22 years, in their descendants (21.7 +/- 1.6 years old, n = 17; 10.9 +/- 0.7 years old; n = 19), and in respective control groups, paired in age and sex. All of the alcoholics presented high 3H-serotonin uptake (Vmax = 10.88 +/- 4.23 pmoles/10(8)pl/30 sec., vs. 0.93 +/- 0.15 pmole/10(8)pl/30 sec. Their descendants also showed high platelet serotonin uptake: 3.94 +/- 1.44 pmoles/10(8)pl/30 sec., vs. 0.93 +/- 0.15 pmoles/10(8)pl/30 sec. for adult descendants, and 5.99 +/- 2.23 vs. 0.84 +/- 0.15 pmole/10(8)pl/30 sec. for young descendants. All subjects were free of alcoholisation (biological parameters studied were blood ethanol concentration, gamma glutamyl transferase and mean corpuscular volume), and dependence of former alcoholics was evaluate by using, a posteriori, the CAGE test. In descendants, 28% of the subjects have Vmax values higher than the highest of the control group. Alcohol, in vitro, (54 mM) did not affect serotonin uptake in any group. These results indicate that in descendants of alcoholics, platelet serotonin uptake is altered, without modification of sensitivity to ethanol. The genetic basis of alcohol dependence could be linked with the platelet serotonin transport.

Evaluation of carbohydrate-deficient transferrin compared with Tf index and other markers of alcohol abuse.

It has been known for some years that a partial deglycosylation of transferrin occurs in the sera of alcohol abusers. Different methods have been proposed in order to evaluate this carbohydrate-deficient fraction of serum transferrin. Chromatofocusing or isoelectric focusing followed by direct immunofixation have been used until now. Recently, a new method called the carbohydrate-deficient transferrin (CDT) test based on ion-exchange chromatography has been developed by Stibler et al. (Alcohol Clin Exp Res 10:535-544, 1986). Here we compare this new method with results obtained using our Tf index determination method. The upper limit of normal values was set to the 90th percentile of the values observed in a reference population. The population under investigation consisted of 50 healthy volunteers and 160 alcohol abusers whose ethanol consumption was evaluated through a questionnaire. Sensitivity and specificity of the CDT test have been found higher than 0.76 and 0.90, respectively. The correlation between both methods was 0.794, a satisfactory result considering that the CDT test and the Tf index do not exactly measure the same part of the carbohydrate-deficient transferrin. In a population of 23 patients with liver diseases not related to alcohol abuse, no abnormal CDT value was observed. We can conclude from these results that the CDT test now seems to be the best test to detect alcohol abusers.

Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients.

129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.

The decrease of low serum gamma glutamyl transferase during short-term abstinence.

We present a study of 107 in-patients of a detoxification center. As expected, 81 percent of them showed upon admittance an increased serum gamma glutamyl transferase (GGT). After alcohol withdrawal, GGT decreased in all but one of these patients. More surprisingly, even among the rest of the patients exhibiting upon admittance a GGT result within the reference range, there still occurred a significant decrease in 50 percent of the cases. Thus, whether the initial GGT is high or normal, we observed a decrease in 96 patients out of 107, i.e., a sensitivity of 0.90. The decrease test consists in asking a subject to refrain from any alcohol intake during a short period, e.g., seven days. If any significant diminution of serum GGT occurs, the possibility of alcohol abuse should at least be given serious consideration before being rejected. This test was used up to now only when GGT was initially high. The present results show that it can be attempted even when GGT is initially within the normal range, with a sensitivity of 0.90.