Platelet serotonin levels in alcoholic patients: Changes related to physiological and pathological factors

Psychiatry Research, 4715748 Elsevier

57

Platelet Serotonin Levels in Alcoholic Patients: Changes Related to Physiological and Pathological Factors Daniel Bailly, Jean Vignau, Nicole Racadot, Rdgis Beuscart, Dominique Servant, and Philippe J. Parquet Received

December

16, 1991; revised version received September

8. 1992; accepied January

1. 1993.

Abstract. This study investigated platelet serotonin (Shydroxytryptamine; 5-HT) levels and the effects of different physiological and pathological factors in 108 alcoholic patients (alcohol abuse, n = 49; alcohol dependence, n = 59) and 32 healthy control subjects. Platelet S-HT levels were determined by a fluorescentorthophtalaldehyde assay. In patients, platelet 5-HT levels during withdrawal from alcohol and after 2 weeks of abstinence were significantly lower than in control subjects. Among patients, this decrease was enhanced both in alcoholdependent patients and in patients who were depressed during the withdrawal phase, whereas lifetime impulse control disorders (mostly found in alcohol abusers) were associated with comparatively high platelet 5-HT levels (i.e., close to control subjects’ values). These results, which reflect the likely biphasic effect of alcohol ingestion upon 5-HT functioning, are consistent with the dimensional 5-HT hypothesis in psychiatric disorders. Key Words. Alcohol abuse, alcohol depression, Shydroxytryptamine.

dependence,

impulse

control

disorders,

Van Praag et al. (1987) and Lecrubier (1988) recently suggested that a deficiency in the function of the serotonin (5-hydroxytryptamine; 5-HT) system may be implicated in the impulse control disorders that are found in many different types of psychopathological conditions: for example, depressions with suicide attempts (Ashcroft et al., 1966; Bourne et al., 1968; Asberg et al., 1976; Banki et al., 1984) antisocial personality disorder, obsessive-compulsive disorders (Yaryura-Tobias et al., 1977; Price et al., 1987; Zohar et al., 1988), bulimia (Kaye et al., 1984; Wurtman and Wurtman, 1986; Hudson and Pope, 1987), and alcoholism (Banki, 1978; Rolf et al., 1978). Drinking behaviors are closely connected to impulsive behaviors. Alcohol has disinhibitory effects, and it facilitates impulsive and aggressive behaviors. In addition, drinking behaviors in themselves may also be regarded as impulsive behaviors. This may explain the close relationship of alcoholism with antisocial behavior and sociopathy (Winkler et al., 1954; Schuckit, 1973; Hesselbrock et al., 1985).

Daniel Bailly, M.D., is Professor of Psychiatry; Jean Vignau, M.D., and Dominique Servant, M.D., are Clinical Assistants; and Philippe J. Parquet, M.D., is Professor of Psychiatry, Psychopathology and Alcohology Unit, University Hospital, Lille, France. Nicole Racadot, M.D., is Assistant, Biochemistry Department, University Hospital, Lille, France Regis Beuscart, M.D., is Professor of Biomathematics, Informatics Department, Faculty of Medicine, Lille, France. (Reprint requests to Dr. D. Bailly, Psychopathology and Alcohology Unit, University Hospital, 57 Bd de Metz, 59037 Lille Cedex, France.) 0165-1781/93/$06.00

@ 1993 Elsevier Scientific

Publishers

Ireland

Ltd

58 Although Banki (1978) and Rolf et al. (1978) reported that platelet 5-HT levels are decreased in alcoholic patients, there have been no further studies of this phenomenon. However, recent studies have suggested that platelet 5-HT content is closely related to platelet 5-HT storage and transport and that it may reflect 5-HT uptake mechanisms (Ortiz et al., 1988). Kent et al. (1985) found a decrease of [3H]5-HT uptake in alcoholic men (alcoholic dependence, n = 19) in the 2-week period following the beginning of abstinence. Using a different method of [3H]5-HT uptake determination, Boismare et al. (1987) found an increased platelet affinity for serotonin (lower K,) in 10 alcoholic patients after 3 weeks of abstinence. Blood platelets seem to provide a good model of the functioning of monoaminergic neurons (Dreux et al., 1979; Van Hahn et al., 1980). However, platelet 5-HT levels are affected by multiple physiological and pathological factors, which must be considered in the interpretation of biological findings. The current study examined platelet 5-HT levels in relationships to different physiological and pathological processes in alcoholic patients and control subjects. Methods Subjects. The sample comprised 140 subjects, all of whom provided informed consent after a full explanation of the nature of the study. The control group consisted of 32 healthy volunteers (15 men and 17 women), aged 22 to 83 years (mean age = 36 years). The patient group comprised 108 alcoholic patients (73 men and 35 women), aged 18 to 66 years (mean age = 39.9 years). The patients received DSM-III (American Psychiatric Association, 1980) diagnoses of alcohol abuse (n = 49) or alcohol dependence (n = 59). No patient had any other psychiatric or organic disease. Routine laboratory tests were performed at the beginning of the study to eliminate severe organic dysfunctions, especially severe impaired liver function. Treatment during the period of withdrawal from alcohol consisted of appropriate hydration and. if necessary, the administration of clorazepate. All patients had a standard evaluation of their alcoholism history, including age of onset, daily alcohol consumption. biological markers (y-glutamyltransferase and mean corpuscular volume), and history of alcoholism in first-degree biological relatives. In addition, all patients underwent a semistructured interview evaluating their psychiatric lifetime history. Particular attention was paid to impulse control disorders (including impulsive behaviors, aggressive behaviors. and suicide attempts) and major depressive episode (according to DSM-III criteria). The possible occurrence of those two conditions during the course of the study was specifically reexamined after 2 weeks of abstinence (on day IS) in a second semistructured interview. Clinical raters were unaware of the laboratory results. Neither alcoholic patients nor control subjects were taking medications, especially those that might interfere with the laboratory results, at least 15 days before the study. None was on a special diet. Nutritional state, calculated with the body mass index, was normal for each subject. Laboratory Tests. Platelet 5-HT levels were determined in each patient during withdrawal (day I ) and after 2 weeks of abstinence (day 15). All the blood samples (in control subjects and alcoholic patients) were taken during a 6-month period. Platelet 5-HT level was determined by a fluorescent-OPT (orthophtalaldehyde) assay (Sommerville and Hinterberger. 1975). All subjects were studied after an overnight fast. A blood sample was collected at 8:30 a.m. (8:25-8:35 a.m.) in a plastic tube containing EDTA and immediately centrifuged for 15 minutes at 8OOg to obtain platelet-rich plasma. After a platelet count, this plasma was centrifuged at 3.5OOg. The supernatant was discarded and the sediment placed in a known volume of lOYe perchloric acid. This platelet suspension was frozen until assay to facilitate platelet destruction and 5-HT release. For assay, the solution was thawed, centrifuged to

59 eliminate platelet fragments, and then put through the orthophtalaldehyde reaction with cysteine in a boiling water bath. The reaction was stopped by addition of periodic acid and the fluorescence measured at 470 nm after excitation at 358 nm. Results are expressed in ng/ 109 platelets (ng/ lo9 pl). Statistics. Statistical comparisons between groups were performed by variance analysis (general linear modeling-GLM procedure) or Student’s t test, Wilcoxon’s nonparametric test when sample size was under 25, and Pearson’s correlation test or x* test when appropriate.

Results Clinical Characteristics of the Alcoholic Patients. Table 1 presents the clinical characteristics of the 108 alcoholic patients. These characteristics are consistent with most of the studies in clinical alcoholic populations. In particular, the 18% lifetime depression prevalence and 10% incidence of current major depressive episode at day 15 found in our population is in accord with a report by Dorus et al. (1987), who also

Table 1. Clinical characteristics of the 108 alcoholic patients: Comparisons between alcohol abusers and alcohol-deoendent subiects Alcoholic patients Controls (n= 32)

Total sample (n = 108)

36.0 + 20.2

39.9 + 10.6

Alcohol abuse (n = 49)

Alcohol dependence (n = 59)

Demographic characteristics Age (yr)

Sex (F/M)

17Fi15M

35Fl73M

39+11

40+11

17Fl32M

18FI41 M

Alcohol history Age of onset (yr)

22.2 +

8.4

24.7 f 10.4’

20.3 f

Duration (yr)

17.7 *

9.7

15.2 +

19.8 zt 9.6

Daily consumption

(g of pure alcohol)

Alcoholism in first-degree Biological

relatives

9.32

5.8

239 * 123

239 + 123

31 (63%)

21 (63%)

41 (69%)

229 + 369

141 f 2743

302 + 420

276f147

markers

y-Glutamyltransferase Mean corpuscular

Impulse control

(Ulil)

volume @)

IOlf

6

74

102*

5

disorders

Lifetime

27 (25%)

During the course of the study

10 ( 9%)

Major depressive

99 +

17 (35%)5 7 (14%)

10 (17%) 3

( 5%)

episode

Lifetime

20 (18%)

11 (22%)

At day 15 of the study

11 (10%)

8 (16%)

9 (15%) 3

( 5%)

Mean platelet serotonin levels (rig/l OSpl) Day 1 Day 15

4751t217

312 + 167’

357.6 + 1 766

274.2 f 150

328 f 174”

375.2 f 198’

288.4 + 141

Note. Abuse vs. dependence: 1. t = 2.5, p < 0.05; 2. t = -2.4, p < 0.05; 3. f = -4.2, p < 0.0001; 5. ,y* = 4.5, p < 0.05; 6. t = 2.0, p < 0.05; 7. t = 2.6, p < 0.05. Controls vs. alcoholic patients: ** t = -4.3, p < 0.0005.

4. t = -3.0, p < 0.005; * t = -4.7. p < 0.0005;

60 found an 18% lifetime depression prevalence and 16% current depression incidence (as defined by the Beck Depression Inventory) at day 24 of alcohol withdrawal. In the same way, we found 25% (35% in men and 17% in women) lifetime impulse control disorders in our population. Patients with a history of impulse control disorders can be compared to “antisocial personality” populations described by other investigators (e.g., Woodruff et al., 1979; Penick et al., 1984; Hesselbrock et al., 1987) who found the prevalence of sociopathic personality among alcoholics to be as high as 20-49s. As expected, in our study, both current depression and impulse control disorders correlated with their respective occurrence in the past (depression: ~2 = 23.85, df = 1,~ < 0.001; impulse control disorders: x2 = 7.2, df = 1, p < 0.01; see Table I for sample sizes). Comparisons between alcohol abusers and alcoholdependent subjects suggested that a milder level of alcohol intoxication in alcohol abusers was related to characteristics such as a significantly shorter duration of alcohol abuse, and significantly lower mean y-glutamyltransferase level and mean corpuscular volume. In addition, impulse control disorders were found significantly more frequently in the personal histories of alcohol abusers. Platelet 5-HT Levels in Alcoholic Patients and Control Subjects. All reported values are the mean + SD of each group. The mean platelet 5-HT level in control subjects was 475 +_ 217 ng/ lo9 pl. This result is consistent with previously reported data (Crosti and Luchelli, 1962; Sommerville and Hinterberger, 1975; Rao et al., 1976; Vatassery et al., 1981). The mean platelet 5-HT levels obtained in patients at day 1 and day I5 were both significantly lower than those in control subjects (day I: 312 + 167 ng/ 109 pl; t = - 4.5, df= 130,~ < 0.0005; day 15: 328 f 174 ng/ lo9 pl; t = -4.0, df= 135, p < 0.0005). These two values were not significantly different when a paired t test was performed, indicating that platelet 5-HT levels did not vary significantly in patients over a 2-week period of abstinence. Platelet 5-HT Levels: Effects of Physiological Parameters. In contrast to the findings of Ortiz et al. (1988) in a group of 175 healthy individuals, no significant correlation was observed between platelet 5-HT level and sex in the control subjects. However, consistent with the study of Ortiz et al. (1988), there was a decrease in the level of platelet 5-HT with age (v = -0.571, p < 0.02). In alcoholics, no significant correlation was found between platelet 5-HT level and sex or age. This suggests that alcohol abuse or dependence might be the basic factor involved in the platelet 5-HT decrease that was observed in these patients. Platelet 5-HT Levels: Effects of Clinical and Biological Factors. Mean platelet 5-HT levels were significantly lower in the alcohol-dependent subjects than in the alcohol abusers (day 1: 274 f 150 ng/ 109 pl in the alcohol-dependent group vs. 358 + 176 ng/ 109 pl in the alcohol abuse group, t = 2.0, df= 101, p < 0.05; day 15: 288 + 141 ng/ 10q pl in the alcohol-dependent group vs. 375 + 198 ng/ 10” pl in the alcohol abuse group, t = 2.6, df= 84, p < 0.05). Variance analysis (GLM procedure) revealed no significant difference in platelet 5-HT levels between day 1 and day 15 in either the alcohol-dependent patients or the alcohol abusers. Duration of alcoholism, daily alcohol consumption, and the existence of alcoholism in first-

61 degree relatives all showed no influence on platelet 5-HT levels at day 1 or day 15. The two biological markers of alcoholism, y-glutamyltransferase level and mean corpuscular volume, were inversely correlated with day-l platelet 5-HT level (y-glutamyltransferase: v = -0.27, p < 0.01; mean corpuscular volume: v = -0.24, p < 0.05). At day 15, only y-glutamyltransferase level was significantly correlated with platelet 5-HT level (v = - 2.6, p < 0.01). These results are consistent with the lower platelet 5-HT levels found in alcohol-dependent patients as compared with alcohol abusers since y-glutamyltransferase level and mean corpuscular volume were significantly higher in the alcohol-dependent population (Table 1). The prescription of clorazepate in 38 cases of severe withdrawal symptoms did not significantly influence mean platelet 5-HT levels according to group-to-group comparisons. This result is consistent with previous data (Lingjaerde, 1978). Platelet 5-HT Levels: Effects of Pathological Conditions. The occurrence, in 10 cases, of impulse control disorders during the study did not significantly modify mean platelet 5-HT levels, whereas the existence of such a disorder in the lifetime of patients (27 cases) was associated with increased mean platelet 5-HT levels (day 1: 399 f 212 ng/ 109 pl vs. 284 + 141 ng/ 109 pl; F= 9.8, p < 0.005; day 15: 420 f 197 ng/ 109 pl vs. 297 f 155 ng/ 109 pl; F = 8.2, p < 0.005). Variance analysis (GLM procedure) did not show any difference in platelet 5-HT levels between day 1 and day 15 in these patients (Table 2). Furthermore, the lifetime occurrence of impulse control disorders correlated with other significant differences in various physiological and pathological parameters: patients with a lifetime history of impulse control disorders were significantly younger (mean age of 33.4 vs. 42.0; p < O.OOOS),their mean length of drinking behavior was lower (12.2 vs. 19.4; p < O.OOOS), alcohol dependence was less frequent (37% vs. 61%; p < 0.05); and biological markers were more mildly affected, but both incidence of current impulse control disorders and a positive history of depression were significantly more frequent. Conversely, alcoholics with a lifetime history of impulse control disorders showed no difference in sex ratio, age of onset, amount of alcohol consumption, alcoholism in first-degree relatives, and incidence of current depression when compared with alcoholics free of a lifetime history of impulse control disorders. Major depression detected in personal history was not related to changes in mean platelet 5-HT levels. However, the appearance of a current major depressive episode during withdrawal (i.e., diagnosed at day 15, after 2 weeks of abstinence) was congruent with an important and significant decrease of mean platelet 5-HT values between day 1 and day 15 (346 f 248 ng/ lo9 pl to 223 + 258 ng/ 109 pl; GLM procedure, F = 11. I; p < 0.002). This dynamic variation of platelet 5-HT level was the only one that was observed among all the parameters analyzed. Discussion This study investigated changes in the platelet 5-HT level observed in alcoholic patients according to different criteria. Previous studies have reported a decrease of platelet 5-HT content in alcoholic patients. However, comparisons and conclusions are difficult to draw because of the diversity of assay procedures used and the

62

Table 2. Clinical characteristics of the 108 alcoholic patients: Comparisons between patients with history of lifetime impulse control disorders (ICD) and oatients free of such a historv Alcoholic patients (n = 108) Without lifetime ICD (n = 81) Demographic characteristics Mean age (yr)

42.0 i

Sex (F/M)

10.5’

22Fl64M

With lifetime ICD (n = 27) 33.4 * a.3 7Fi20M

Alcohol history Mean age of onset (yr)

22.6 f 10

Mean duration

19.4 f 9.5’

i 2.2 k a.2

248.6 + 138

295.5 + 134

(yr)

Mean daily consumption Alcoholism Alcohol

(g of pure alcohol)

in first-degree

relatives

dependence

21.1 f a.2

66%

77%

61 %*

37%

Biological markers y-Glutamyltransferase Mean corpuscular

(WI) volume

(logarithm) (J?)

4.7 Ifr 1.33

3.9 * 1 .l

101.4 * 7.04

96.4 i 3.7

Pathological depression Current

ICD

5%**

Lifetime major depression Current

major depressive

episode

22%

ll.l%*”

40.7%

7.4%

i 8.5%

Mean platelet serotonin levels (ngil O9 pl) Day 1

284 + 1415

399+212

Day 15

297 + 1556

420 k 197

Note. Comparrsons by 5. t = 2.5, p < 0.005; 6. D < 0.005.

t test: 1. t = 4.3, p t = -3.3, p < 0.005.

< 0.0005; 2. Comparisons

t = 3.3,

p < 0.0005, 3. t = 3.1, p < 0.005. 4. t = 2.6, p < 0.01; by x2 test: * Y = 4 5. p < 0.05; ** v = 7 2, p < 0.01: “* v = 11.8,

of the populations studied. In addition, previous reports showed that platelet 5-HT levels vary according to several physiological parameters (Fernstrom and Wurtman, 1971, 1972). In the present study, alcoholic patients had a significantly lower mean platelet 5-HT level than that found in control subjects. This finding is consistent with previously reported data (Banki, 1978; Rolf et al., 1978) and does not appear to be due to age, sex, weight, or prior alcohol consumption. It is also not likely to be due to clorazepate administration, which has been reported to have no influence on 5-HT transport (measured by platelet 5-HT uptake) (Lingjaerde, 1978). Food intake (standard hospital diet) has no significant effect on platelet or whole blood S-HT (Anderson et al., 1985; Ortiz et al., 1988) and thus was not addressed as a relevant variable in our study. As far as alcoholism history is concerned, no significant change in platelet 5-HT was observed in patients whose first-degree relatives were alcoholic. Length and amount of alcohol abuse did not correlate with platelet 5-HT. We can postulate that these two variables are not relevant because the mean values given by alcoholic patients are approximate and subjective. Morever, there are wide individual heterogeneity

63 differences in susceptibility to the metabolic repercussions of excessive alcohol consumption. On the other hand, the occurence of an alcohol dependence is an objective clinical feature and seems to be relevant. We found a significantly more marked decrease in the level of platelet 5-HT activity in the alcohol-dependent subgroup as was observed in a previous work (Bailly et al., 1990). In addition, specific conditions such as depression or impulse control disorders were less frequently found in the alcohol-dependent subgroup, whereas alcohol intoxication was more severe compared with the alcohol abuse subgroup. It is difficult to compare these findings with those in the literature because most of the previous reports included only alcohol-dependent populations or individuals with “chronic alcohol consumption.” Alcohol seems to have a biphasic effect on serotoninergic functioning. In vivo, acute administration of alcohol to rats or mice has a reserpine-like action in releasing 5-HT (Bonnycastle et al., 1962; Rowat, 1974; Badawy and Evans, 1976). On the other hand, chronic alcohol consumption seems to result in an adaptive “vicious cycle” that leads to 5-HT depletion (Ballenger et al., 1979; Kent et al., 1985). This could be the underlying mechanism of alcohol dependence, and may explain the platelet 5-HT decrease observed in our alcohol-dependent subpopulation. Alcoholic patients could be divided into two categories on the basis of their personality features: alcohol-dependent subgroup with ordinary personality (or excessive social conformity or inhibition, at the most) vs. alcoholic subgroup with antisocial behaviors and acting-out or suicidal tendencies (i.e., impulse control disorders). Our patients with impulse control disorders can be compared to the type 2 alcoholics previously described by Cloninger and his associates (Bohman et al., 1981; Cloninger et al., 1981). Cloninger’s subtypes of alcohol abusers were derived from data (severity of abuse and criminality) collected in a study of adopted men, thus clearly differentiating environmental from genetic influences. Our population appreciably differed from Cloninger’s: we did not specifically assess the severity of alcoholism; both men and women were included; none of the patients were adopted; criminality was just a part of our criteria for impulse control disorders. Despite these important discrepancies, it should be noted that we obtained about the same proportion of subjects with lifetime diagnoses of impulse control disorders (25%) as Cloninger found of type 2 alcoholics (24%). The alcoholic patients with lifetime impulse control disorders were hospitalized earlier (lower mean age of admission) than those who lacked such a history. Their drinking history was also shorter, and dependence was half as frequent. In addition, more of these patients had either suffered from depression in the past or exhibited a major depressive episode diagnosed on day 15. The combination of aggression and depression was previously reported to correlate with a marked decrease of tryptophan (precursor of serotonin) availability in alcohol-dependent patients (BuydensBranchey et al., 1989). Buydens-Branchey et al. (1980) also observed that this decrease (1) was significant in the subjects who had started abusing alcohol before 20 years of age and (2) was maximum 1 day after the beginning of abstinence and then diminished over the

64 following 2 or 3 weeks. We observed a slight but not significant increase in platelet serotonin depletion in the total sample and in the various subpopulations (related to lifetime impulse control disorders or alcohol dependence). Because the significant factor identified by Buydens-Branchey et al. (1989)-onset of alcohol abuse before age 20-is strongly affected by environmental factors (influencing the probability of encountering alcohol), it was not considered as a relevant variable for the issue of alcohol abuse inheritance in our study. For instance, a high proportion of our alcoholic men declared they had started alcohol consumption during their military service when, in France, the age of compulsory conscription is fixed (around 20 years). Previous studies have emphasized likely correlations between central serotoninergic deficiency and both human impulsive disorders (Linnoila et al., 1983; Lidberg et al., 1985; Moss, 1987; Roy et al. , 1987) and alcohol preference in rats (Ahtee and Ericksen, 1973; Myers and Martin, 1973; Hill, 1974; Naranjo et al., 1986). Since the life of circulatory platelets is 8-10 days and platelet 5-HT levels remain low in alcoholic patients after 2 weeks of abstinence, we can hypothesize that alcoholics may be basically affected by a serotoninergic dysfunction. In such a case, alcohol would temporarily improve this serotoninergic dysfunction (Bonnycastle et al., 1962; Feldstein et al., 1967; Tabakoff and Boggan, 1974; Badawy and Evans, 1976). However, the etiologic significance of this serotoninergic dysfunction may differ according to alcohol use disorders. In alcohol abusers who are free of impulse control disorders, it may underlie alcohol preference, the repetition of alcohol consumption that slowly leads to secondary alcohol dependence (“vicious cycle” as described above) and to an accentuation of central serotoninergic deficiency (Bailly et al., 1990). This may explain why platelet 5-HT levels in alcohol-dependent patients were lower than those in alcohol abusers. In alcohol abusers affected by impulse control disorders, basal serotoninergic dysfunction may underlie impulsive behaviors, including drinking. Consistent with the results obtained in our 27 patients with lifetime impulse control disorders, the existence of impulse control disorders associated with an irregular consumption of alcohol may result in an earlier resort to hospital treatment, before the beginning of the alcohol-dependence process (Bailly et al., 1990). However, our study design does not permit us to draw any definitive conclusions. It would be especially interesting to study the patients at different times during the evolution of their disorders to see whether alcohol abuse and alcohol dependence actually affect two very different groups of subjects or conversely represent two developing stages of the same disorder. In 11 patients, the concomitant appearance of a depressive condition and a 5-HT decrease in the early period of alcohol abstinence is consistent with previous studies showing a deficit of 5-HT availability in depressive patients (Ashcroft et al., 1973; Takahashi, 1976; &berg et al., 1984). The possible involvement of a 5-HT deficit in withdrawal-emergent depression may have implications for the choice of a proper antidepressant treatment. Relationships between alcoholism and affective disorders are complex. To understand them, it seems important to distinguish between sadness and major affective disorder: sadness and even intense transient secondary affective episodes are often seen in the course of alcoholism, whereas alcoholism and major affective

65 disorder appear to be independent diseases (Schuckit, 1983a, 1986). Since lifetime depression was found in our study to be closely related to the occurrence of a major depressive episode after 2 weeks of abstinence, we can postulate that the depressive condition may be a third specific expression of the basal serotoninergic dysfunction observed in alcoholics. In such a case, acute alcohol consumption might temporarily improve affective state (Mayfield, 1968; Gibson and Becker, 1973), even if persistent heavy drinking is likely to precipitate symptoms of depression (Schuckit, 19836). However, whether serotoninergic deficiency is a vulnerability factor of depression remains debatable, since 5-HT uptake studies in recovered depressed patients have shown both a persistent decrease (Coppen et al., 1978) and an increase (Scott et al., 1979) of 5-HT uptake levels.

Conclusions Our study suggests that alcoholic patients may be affected by a basal serotoninergic dysfunction that is secondarily aggravated through an adaptive “vicious cycle” related to the development of alcohol dependence. However, consistent with the hypotheses of Van Praag et al. (1987) and Lecrubier (1988), this serotoninergic dysfunction may have various clinical expressions according to psychopathological factors: dependent personality, antisocial personality, or depressive tendencies. The comparative importance of these factors, which may be associated, in addition to the occurrence of alcohol dependence, may explain the diversity of psychological and biological profiles observed in alcoholic patients. However, since our results emerged from a short-term study design, further investigations need to be done to confirm these preliminary suggestions.

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