Extremely long recovery time for the sedative effect of clonidine in male type 1 alcohol-dependent subjects in full sustained remission.

The possible relation between alpha-2-adrenoceptor function-as assessed by changes in systolic and diastolic blood pressure and heart rate, as well as level of sedation, after administration of clonidine (2.0 microg/kg, i.v.)-and length of time of alcohol dependence or duration of remission was investigated in 17 male subjects with alcohol dependence in full sustained remission. Six healthy males were used as control subjects. The clonidine-induced scores for level of sedation were found to correlate with duration of time in remission (r = 0.60; P <.02). Median split of duration of remission revealed that subjects with short-term (2 +/- 1 years) duration of remission had significantly lower scores for clonidine-induced level of sedation than the scores for both subjects with long-term (12 +/- 5 years) duration of remission (P <.004) and control subjects (P <.02). There was also a significant correlation between duration of remission and values for clonidine-induced reduction of systolic blood pressure (r = 0.51; P <.05). Results indicate an extremely long recovery period in some aspects of alpha-2-adrenoceptor function, especially for clonidine-induced increase in level of sedation, with a normalization time of 4 to 5 years.     

Platelet monoamine oxidase B in family history positive and family history negative type 1 alcohol-dependent subjects

- 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.     

Platelet monoamine oxidase activity in type 1 and type 2 alcoholism.

Earlier studies have identified at least two distinct subtypes of alcoholism. Type 2 is characterised by high heritability, early onset, frequent social complications and mixed misuse. With regard to temperament, the type 2 alcoholics score high in impulsiveness and sensation-seeking behaviour. Type 1 alcoholics have a later onset, lower degree of heritability and rarely there is misuse of illegal drugs. In the present study, 37 type 1 and 62 type 2 male alcoholics were compared with 36 male controls with regard to platelet monoamine oxidase (MAO) activity, which is a stable biological marker, inversely correlated to personality traits such as impulsiveness and sensation seeking. The platelet MAO activity was found to be lower in type 2 alcoholics when compared both with healthy controls and with type 1 alcoholics. Also, the type 1 alcoholics had lower platelet MAO activity than the controls. The result confirms a previous study and validates the subclassification of alcoholism according to the type 1 and 2 concept. This should be of value for future studies concerning etiology, epidemiology, treatment and prevention of alcoholism.     

Different effects of smoking or use of smokeless tobacco on platelet MAO-B activity in type 1 alcohol-dependent subjects

BACKGROUND: Low platelet monoamine oxidase (MAO)-B activity has been proposed as a marker for alcohol-dependence. Findings are, however, contradictory and the influence of confounding factors have been thoroughly investigated. Thus, it is now well established that cigarette smoking reduces platelet MAO-activity. However, not much is known about the influence of smokeless tobacco, i.e. snuff or chewing tobacco, on platelet MAO-B activity. The aim of the present study was to compare platelet MAO-B activity in type 1 alcohol-dependent subjects with concomitant use of smokeless tobacco (i.e. snuff users), use of smoking tobacco (i.e. cigarette smokers), and in those without any tobacco use. METHODS: Platelet MAO-B activity was examined in three groups of alcohol-dependent subjects: snuff users (n = 14), cigarette smokers (n = 33), and non-tobacco users (N = 46). RESULTS: In the alcohol-dependent subjects concomitant cigarette smokers, but not snuff users, were found to have significantly lower platelet MAO-B activity as compared to non-tobacco users (platelet MAO-B activity 4.0 +/- 1.5, 5.1 +/- 1.5 and 5.0 +/- 1.9 microkat/kg protein, respectively). CONCLUSIONS: The findings in the present study suggests that in the alcohol-dependent subjects the concomitant use of smokeless tobacco, i.e. snuffing, does not have an inhibitory effect on platelet MAO-B activity. This may have implications for future research. Thus, alcohol-dependent subjects with concomitant tobacco use should be grouped separately according to the form of the tobacco used, i.e. smoking or smokeless tobacco.     

Subnormal alpha-2-adrenoceptor-mediated sedation during 6 months of sobriety in male type 1 alcohol-dependent subjects

AIMS: In the present study, alpha(2)-adrenoceptor function was investigated over 6 months of sobriety in eight male alcohol-dependent subjects. METHODS: Subjects were investigated with repeated clonidine (CLON, 2 micro g/kg body weight intravenously) challenge tests at days 1 and 7, and months 2 and 6 after the end of a period of heavy alcohol intake. CLON-induced sedation was rated at challenge tests. Mental well-being was self-reported before all challenge tests. Three challenge tests were performed at 1-week intervals in six male healthy controls. RESULTS: Sedation was significantly lower after CLON at all time-points for the challenge tests in alcohol-dependent subjects compared with mean values for three challenge tests in controls. Three dimensions of mental well-being were negatively correlated with scores of CLON-induced sedation at month 6. CONCLUSIONS: alpha(2)-Adrenoceptor function is subnormal, as assessed by CLON-induced sedation, for at least 6 months after termination of alcohol intake. Whether this subnormal receptor function is pre-existing and possibly genetically determined or is a consequence of long-term alcohol intake must be further investigated, as should this receptor status in alcohol-dependent subjects with longer time-periods of sobriety.     

Platelet monoamine oxidase B activity in workers exposed to styrene

A cross-sectional study was conducted to evaluate monoamine oxidase type B (MAO-B) activity in platelets as a biomarker of effect of styrene and perchloroethylene exposures. MAO-B is an enzyme system involved in dopamine catabolism, the impairment of which has been postulated as a mechanism of styrene-induced neurotoxicity. We previously observed an inverse association between blood styrene and MAO-B among reinforced plastics manufacturing workers. The present study included 59 male boat plant workers exposed to styrene (exposure range < 1–144 ppm, 8-h TWA). Two comparison groups comprised six male dry cleaning workers exposed to perchloroethylene (PCE; exposure range < 2-37 ppm) and 14 male laundry workers not exposed to either agent. Respiratory protection was not used by any of the styrene- or PCE-exposed workers; thus, air concentrations were regarded as valid exposure indicators. MAO-B activity (pmol/10⁸ cells/h) was measured in peripheral blood platelets, using phenylethylamine as substrate. Only small overall mean differences in MAO-B were observed among the three groups; mean values were 4.21, 4.51, and 4.12 for the styrene-exposed, PCE-exposed, and laundry workers, respectively. Despite the absence of gross differences among the groups, styrene exposure was inversely related to MAO-B. Mean values for four increasing exposure group quartiles were: 5.60, 4.13, 3.69, and 3.44. The Spearman rank correlation coefficient for styrene with MAO-B was –0.41. Adjustment for age, medication use, smoking, and alcohol consumption had only a minimal effect on this trend. Duration of exposure to styrene bore a weak positive relation to MAO-B (Spearman r = + 0.29), which was nearly entirely explained by collinearity with age. The results from this study are in close quantitative agreement with previous findings of an inverse association between styrene exposure and MAO-B. More agents need to be evaluated to establish specificity, and longitudinal analyses of styrene-exposed workers will be required before confident conclusions can be reached about the predictive value of MAO-B as a biomarker of styrene-related neurotoxicity.     

Impulsivity in abstinent alcohol-dependent patients: relation to control subjects and type 1-/type 2-like traits.

Extensive literature has linked behavior control problems in childhood to risk for alcoholism, but impulsivity in alcohol-dependent adults has not been well characterized. Using a variety of laboratory measures of impulsivity, we assessed whether detoxified alcohol-dependent patients [(ADP); n = 130] were more impulsive than control subjects [(CS); n = 41]. In comparison with CS, ADP demonstrated (1) increased rates of commission errors, but not omission errors, in a continuous performance test, (2) a more severe devaluation of delayed reward, (3) increased rates of risky responses in a new risk-taking paradigm, and (4) higher psychometric scores of impulsivity and aggression. Across all subjects, aggressiveness correlated significantly with severity of delay discounting. A post hoc analysis of data obtained for male ADP indicated that, in comparison with patients with late onset of problem drinking and no problem-drinking parent, those ADP with earlier age of problem drinking and who reported a problem-drinking father (type 2-like alcohol dependence) demonstrated faster response latencies and more responses to non-target stimuli (commission errors) in the continuous performance test, as well as higher psychometric aggression. In contrast, these subtypes of male ADP did not differ in delay discounting and risk taking. These findings collectively indicate that, in comparison with CS, ADP are more impulsive in several dimensions, with elevated impulsivity in a working memory task as well as aggressivity characteristic of alcohol-dependent men with type 2-like features.     

Platelet serotonergic binding sites in alcohol-dependent patients.

The serotonin (5-hydroxytryptamine, 5-HT) uptake sites assessed with both [3H]imipramine and [3H]paroxetine, and the 5-HT2A receptors were simultaneously measured in platelets from 24 male subjects meeting the American Psychiatric Association's DSM-IV criteria for alcohol dependence and admitted for inpatient detoxification. Blood samples from alcoholic patients were collected during acute alcohol intoxication (day 0), during withdrawal (day 1), and after 2 weeks of abstinence (day 14). All patients met the criteria for type II alcoholism. Alcohol misuse was found to be associated with an increased number and a lower affinity of [3H]paroxetine binding in comparison to the control values. Abstinence from alcohol for 2 weeks (day 14) resulted in a decrease in the number of 5-HT uptake sites labelled with [3H]paroxetine compared to normal values, together with a significant decrease in the number of 5-HT2A binding sites. The present data indicate that altered serotonergic function existing in alcoholic patients is a reversible phenomenon that normalizes after detoxification and withdrawal.     

Quality of Life in alcohol-dependent subjects – a review

Although alcohol misuse is a major cause of morbidity and mortality and an important health care burden, the Quality of Life (QoL) of alcohol misusing subjects has been little studied to date. For example, only 5 out of 442 accepted abstracts at a recent international QoL conference concerned alcohol-dependent subjects. This paper reviews the ongoing and published work in the area focusing upon QoL characteristics of alcohol-dependent subjects, the link between QoL comorbidity and alcoholism, QoL alcohol dependency and social environment, changes in QoL status as a result of abstinence, minimal or controlled drinking, QoL as a predictor of relapse to heavy drinking and the importance of using a QoL measure when assessing treatment outcomes together with some of the present difficulties with existing measures. The main conclusions from the review were that the QoL of alcohol-dependent subjects is very poor but improved as a result of abstinence, controlled or minimal drinking. The important factors in the QoL of alcohol-dependent subjects are psychiatric comorbidity, social environment and disturbed sleep.     

Alcohol-dependent patients with neuroendocrine evidence for reduced dopamine d(2) receptor function have decreased platelet monoamine oxidase-B activity

This letter is a report of a re-evaluation of the results obtainedin an earlier study of ours (Balldin et al., 1994) of plateletmonoamine oxidase (MAO)-B activity in alcoholics with reduceddopamine (DA) D₂ receptor function, as assessed by the growthhormone (GH) response to the D₁/D₂ agonist apomorphine (APO),which was published in this journal. The reason for the re-evaluationof the results in our study is a Letter to the Editors of thisjournal by Farren and Dinan (1996) reporting on platelet MAO-Bactivity in alcoholics with reduced DA D₂ receptor function,as assessed by the GH response to the DA D₂ receptor agonistbromocriptine. In the report by Farren and Dinan (1996), fourof eight alcoholics had no increase in GH above baseline, whereasall eight subjects in the control group had the expected GH. . . [Full Text of this Article]FOOTNOTESREFERENCES     

Platelet monoamine oxidase activity in alcoholism subtypes: relationship to personality traits and executive functions

- AIMS: The purpose of the present study was to compare alcoholic subtypes (type 1 versus type 2) with regard to platelet monoamine oxidase (MAO) activity. A possible relationship between enzyme activity, personality traits and executive functions was also investigated. METHODS: Seventeen type 1 and 16 type 2 in-patient male chronic alcoholic patients and 17 healthy male volunteers were included in the study. The personality traits were investigated by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Executive functions were assessed by the Wisconsin Card Sorting Test (WCST). RESULTS: When compared to the healthy subjects, platelet MAO activity was reduced in both alcoholic groups. The enzyme activity of the type 2 group was significantly lower than that of type 1 patients. Both groups of alcoholic patients also displayed impairment in executive functions. The comparison of the MMPI-2 scores of the study groups revealed that type 2 alcoholics had more severe psychopathology. CONCLUSIONS: The results support previous evidence suggesting that platelet MAO activity is a useful biochemical measure for the subtyping of alcoholics.     

Alcoholics with the dopamine receptor DRD2 A1 allele have lower platelet monoamine oxidase-B activity than those with the A2 allele: a preliminary study

Low platelet monoamine oxidase B (MAO-B) activity and the presence of the Taq1 A1 allele of the dopamine D2 receptor (DRD2) gene have independently been proposed as 'biological/genetic' markers for alcoholism. In the present study, the relationship between these two markers was investigated in a group of socially stable Caucasian middle-aged men with a mean (+/-SD) daily ethanol consumption of 85 +/- 57 g. The platelet MAO-B activity was significantly lower in individuals with the DRD2 A1 allele (n = 8), compared to those without it (n = 29). This relationship remained unchanged when including only subjects who fulfilled DSM-IV criteria for alcohol dependence (n = 27). The finding suggests that alcoholics who are carriers of the DRD2 A1 allele may have lower platelet MAO-B activity.     

Platelet and erythrocyte membrane fluidity changes in alcohol-dependent patients undergoing acute withdrawal.

This study tested the hypothesis that membrane fluidity may alter during the alcohol-withdrawal syndrome. Platelet membranes of alcohol-dependent patients (n = 7) were significantly more rigid than controls (n = 7) at the start of alcohol withdrawal (mean fluorescence anisotropy 203.1 x 10(-3) vs 195.5 x 10(-3) respectively, P = 0.03), but were significantly more fluid when withdrawal was complete (191.4 x 10(-3) vs 199.2 x 10(-3), P = 0.03). Consequently platelet membranes of patients adapted to the known acute fluidizing effect of alcohol by becoming more rigid, but underwent a marked fluidization during withdrawal. There were no significant changes in erythrocyte membrane fluidity during withdrawal.     

Measurement of quality of life in alcohol-dependent subjects by a cancer symptoms checklist.

There are few studies of Quality of Life measures (QoL) in alcohol-misusing patients. The present study addresses this deficiency. The sample consisted of 60 (39 men, 21 women) alcohol dependent subjects defined by DSM-IV criteria (American Psychiatric Association, 1994). At baseline (4-5 days after admission and detoxification) sociodemographic data were collected, and three questionnaires were administered: the Rotterdam Symptoms Checklist (RSCL), the Severity of Alcohol Dependence Questionnaire (SADQ), and Alcohol Problems Questionnaire (APQ). QoL scores for dependent alcoholics both for physical and psychological measures were significantly worse (higher) than those reported for a variety of cancer patients. Psychological symptom scores were higher than physical symptoms at baseline. Correlations of RSCL scores to both SADQ and APQ were greater for RSCL physical compared to psychological symptom scores. The subjects were followed up at 12 weeks when the RSCL was re-administered and relapse status ascertained. Fifty-eight (97%) subjects were successfully contacted at 12 weeks of whom 36 (62%) had relapsed. After a repeated measures ANOVA psychological and physical symptom subscores were statistically significantly improved as a result of not relapsing to heavy drinking. There was no significant change in scores in the relapse group when baseline and week 12 scores were compared. The RSCL measure is a useful QoL assessment tool in alcohol-dependent subjects.     

Decreased white matter integrity in fronto-occipital fasciculus bundles: Relation to visual information processing in alcohol-dependent subjects

Chronic alcohol abuse is characterized by impaired cognitive abilities with a more severe deficit in visual than in verbal functions. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The present study sought to increase current understanding of the impairment of visual processing abilities in alcohol-dependent subjects, and its correlation with white matter microstructural alterations, using diffusion tensor imaging (DTI). To that end, a DTI study was carried out on 35 alcohol-dependent subjects and 30 healthy male control subjects. Neuropsychological tests were assessed for visual processing skills and deficits were reported as raw dysfunction scores (rDyS). Reduced FA (fractional anisotropy) and increased MD (mean diffusivity) were observed bilaterally in inferior and superior fronto-occipital fasciculus (FOF) fiber bundles. A significant inverse correlation in rDyS and FA values was observed in these fiber tracts whereas a positive correlation of these scores was found with the MD values. Our results suggest that FOF fiber bundles linking the frontal lobe to occipital lobe might be related to visual processing skills. This is the first report of an alteration of the white matter microstructure of FOF fiber bundles that might have functional consequences for visual processing in alcohol-dependent subjects who exhibit no neurological complications.     

Self-reported exercise and quality of life in young type 1 diabetic subjects

Evaluation of quality of life is important in treatment strategies of chronic illnesses, such as diabetes mellitus. The present study aimed at measuring the impact of self-reported exercise on quality of life in T1DM patients. Fifty-three young T1DM patients on intensive insulin-treatment regime who were regularly attending the Diabetes Clinic were selected. At the end of the scheduled clinic visit, they were asked to fill in an Italian version of the Diabetes Quality of Life (DQOL) questionnaire; 30 patients exercised regularly, whereas 23 were sedentary. Patients with clinical and laboratory evidence of major eye, renal and cardiovascular diseases were excluded. A significant difference in the scale of satisfaction (1.9 +/- 0.3 vs 2.2 +/- 0.5; p = 0.009), along with a better HbA1c level (7.0 +/- 1.0 vs 7.8 +/- 1.2; p = 0.014), was observed in physically active patients as compared to sedentary ones, whereas there were no differences between the 2 groups with respect to the impact and worry scale. Moreover, there were no significant correlations between glucose control parameters and the quality of life scores. In conclusion, we showed that self-reported exercise is associated with both a better quality of life and a better metabolic control in young T1DM patients. Further efforts should however be made to recognize all factors that can help motivate patients to exercise.     

Platelet monoamine oxidase B activity as a state marker for alcoholism: trend over time during withdrawal and influence of smoking and gender

- AIMS AND METHODS: The present study evaluated time-related changes in platelet monoamine oxidase B (MAO-B) activity in an Italian cohort of alcohol-dependent subjects (n = 98) during early abstinence, and the effect of potential confounding factors, such as gender and smoking status, on the temporal trend of the enzyme activity. RESULTS: While still under the influence of ethanol (time point T1), the mean value of platelet MAO-B activity in alcoholics was 6.4 +/- 3.1 nmol/mg of protein/h. This increased by >40% (to 9.3 +/- 4.4 nmol/mg of protein/h) after 8 days of withdrawal (T2), and remained stable thereafter (T3 and T4: 15 and 22 days of abstinence, respectively). In a cohort of 138 healthy subjects, MAO activity levels averaged 9.9 +/- 0.9 nmol/mg of protein/h. In the group of alcoholic patients, alcohol intake cessation was confirmed by the progressive decrease of serum % carbohydrate-deficient transferrin (CDT), which was pathologically above the reference limits (6%) at T1 (7.8 +/- 3.3%), declined to 6.6 +/- 2.1% at T2 and reached physiological values at T3 and T4. In a subgroup of cirrhotic alcoholics, %CDT did not decrease over time, while MAO activity rose after the first week of abstinence, without further change at T3 and T4. During early withdrawal, neither gender nor tobacco smoking affected the temporal pattern of MAO activity. CONCLUSIONS: MAO-B can be regarded as a state marker of alcohol consumption. The temporal pattern of platelet MAO-B activity may be used for the diagnostic assessment of alcoholism and early abstinence, regardless of gender and smoking status.