Alexander Diehl

Neuroimaging of Gender Differences in Alcohol Dependence: Are Women More Vulnerable?

BACKGROUND Alcoholic brain damage has been demonstrated in numerous studies using neuropathology and brain imaging techniques. However, gender differences were addressed only in a few studies. Recent research has shown that development, course, and consequences of alcohol dependence may differ between female and male patients. Our investigation was built upon earlier research where we hypothesized that women develop alcoholic brain damage more readily than men do. To further compare the impact of alcohol dependence between men and women, we examined brain atrophy in female and male alcoholics by means of computed tomography (CT). METHODS The study group consisted of a total of 158 subjects (76 women: 42 patients, 34 healthy controls; 82 age-matched men: 34 patients, 48 healthy controls). All patients had a DSM-IV and ICD-10 diagnosis of alcohol dependence. CT with digital volumetry was performed twice in patients (at the beginning and end of the 6-week inpatient treatment program) and once in controls. RESULTS Patients of both genders had consumed alcohol very heavily. Although the average alcohol consumption in the year before the study was significantly lower in female alcoholics, this gender difference disappeared when controlled for weight. However, women had a significantly shorter duration of alcohol dependence. Despite this fact, both genders developed brain atrophy to a comparable extent. Brain atrophy was reversible in part after 6 weeks of treatment; it did not reach the level in the control groups. CONCLUSIONS Gender-specific differences in the onset of alcohol dependence were confirmed. This is in line with the telescoping effect, where a later onset and a more rapid development of dependence in women were described. Under the assumption of a gradual development of consequential organ damage, brain atrophy seems to develop faster in women. As shown in other organs (i.e., heart, muscle, liver), this may confirm a higher vulnerability to alcohol among women.

Monitoring the Effects of Chronic Alcohol Consumption and Abstinence on Brain Metabolism: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

BACKGROUND This study focused on metabolic brain alterations in recently detoxified alcohol-dependent patients (S1) and their possible reversibility after 3 (S2) and 6 months (S3) of abstinence. METHODS Thirty-three alcohol-dependent patients and 30 healthy control subjects were studied with multislice proton magnetic resonance spectroscopic imaging (echo time = 135 msec at 1.5 T at three time points). RESULTS In the patient group, we found that choline-containing compounds (Ch) in three frontal and cerebellar subregions at S1 were significantly below normal, whereas N-acetyl aspartate (NAA) differences did not reach significance but showed a trend toward below-normal values in frontal white matter. Abstinent patients showed a significant increase of Ch in all subregions at S2. At S3, no further significant metabolite changes in abstinent patients compared with S2 could be detected. No significant increase of NAA could be detected at follow-up. CONCLUSIONS The increase of the Ch signal in the follow-up measurement after 3 months in abstinent alcohol-dependent patients supports the hypotheses of an alcohol- or alcohol detoxification-induced altered cerebral metabolism of lipids in membranes or myelin, which seems to be reversible with duration of alcohol abstinence.

Alcohol consumption significantly influences the MR signal of frontal choline-containing compounds

The aim of this work was to evaluate the relationship between the amount of alcohol consumption of a group of social drinkers and the magnetic resonance spectroscopy signal of choline-containing compounds (Cho) in the frontal lobe. Two independent long echo (TE = 135 ms) (1)H MRSI studies, the first comprising 24 subjects with very low alcohol consumption, the second 18 subjects with a more widespread alcohol consumption were conducted. Significant correlations of Cho measures from frontal white matter and from the anterior cingulate gyrus with alcohol consumption in the last 90 days prior to the MR examination were found. Age, gender, and smoking did not show significant effects on the metabolite measures. Partialling out the effect of the voxel white matter content did not change the correlation of choline measures with alcohol consumption. The main conclusion from the repeated finding of a positive correlation of alcohol consumption and frontal Cho signals is that monitoring for alcohol consumption is mandatory in MRS studies where pathology depended Cho changes are hypothesized.

Cloninger's typology and treatment outcome in alcohol-dependent subjects during pharmacotherapy with naltrexone

Naltrexone is an opiate receptor antagonist mainly at the µ‐receptor that is thought to reduce the positively reinforcing, pleasurable effects of alcohol and to reduce craving. An increase in time to first relapse to heavy drinking has been the most consistent finding obtained with naltrexone, although not all trials including two of the largest have been positive. Inconsistent outcome data suggest that effectiveness varies among different subgroups of patients. This paper re‐evaluates recent data on the effectiveness of naltrexone in subjects differentiated according to Cloninger Type I and II. Moreover, it combines and cross‐validates results of two recent European studies that found naltrexone treatment more beneficial in alcohol‐dependent patients with early age at onset of drinking problems (Cloninger Type II). It is discussed whether especially these subjects should be targeted for pharmacological relapse prevention treatment with naltrexone.

Pronounced paranoia as a result of cocaine-disulfiram interaction: case report and mode of action.

To the Editors: Restless legs syndrome (RLS) is a common neurological disorder characterized by dysesthetic sensations in the legs and irresistible urge to move them. Arm restlessness has been reported as an accompanying feature in up to 48.7% of patients with RLS, although involvement of upper limbs is rarely reported as an initial symptom of RLS. The term restless arms syndrome (RAS) has been proposed for the restlessness of the arms with clinical features similar to RLS. Drug-induced RLS has been described under treatment with various drugs, including the atypical antipsychotics olanzapine, risperidone, quetiapine, and clozapine. However, to the best of our knowledge, there are as yet no reports on drug-induced RAS without RLS. Only 1 case of neuroleptic-induced restlessness of the arms has been reported, however, in the context of akathisia. In the following, we report on such a case whereby RAS developed under treatment with olanzapine.

Neuropsychological Functioning of Opiate-Dependent Patients: A Nonrandomized Comparison of Patients Preferring either Buprenorphine or Methadone Maintenance Treatment

Objectives: In the present study, we investigated whether buprenorphine as a partial μ -opioid receptor agonist is associated with less cognitive impairment than methadone. Methods: Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated. Results: MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task. Conclusions: In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.

Does the degree of smoking effect the severity of tardive dyskinesia? A longitudinal clinical trial.

BACKGROUND Tardive dyskinesia (TD) is a movement disorder observed after chronic neuroleptic treatment. Smoking is presumed to increase the prevalence of TD. The question of a cause-effect-relationship between smoking and TD, however, remains to be answered. Purpose of this study was to examine the correlation between the degree of smoking and the severity of TD with respect to differences caused by medication. METHOD We examined 60 patients suffering from schizophrenia and TD. We compared a clozapine-treated group with a group treated with typical neuroleptics. Movement disorders were assessed using the Abnormal-Involuntary-Movement-Scale and the technical device digital image processing, providing rater independent information on perioral movements. RESULTS We found a strong correlation (.80<r<.90, always p<.0001) between the degree of smoking and severity of TD. Repeated measurements revealed a positive correlation between changes in cigarette consumption and changes of the severity of TD (p<.0001). Analyses of covariance indicated a significant group-effect with a lower severity of TD in the clozapine-group compared to the typical-neuroleptics-group (p=.010). Interaction-analyses indicated a higher impact of smoking on the severity of TD in the typical-neuroleptics-group compared to the clozapine-group (p=.033). CONCLUSION Concerning a possible cause-effect-relationship between smoking and TD, smoking is more of a general health hazard than neuroleptic exposure in terms of TD.

Modifications of the Obsessive Compulsive Drinking Scale (OCDS-G) for use in longitudinal studies

Since the application of the Obsessive Compulsive Drinking Scale (OCDS) has been reported to be problematic when used to measure alcohol craving in longitudinal studies, we examined the following questions: (1) Is it possible to skip problematic quantity items? (2) Is the score calculation rule using the higher value of item pairs necessary? (3) Can the shortened version of the OCDS be applied alternatively? We examined two samples including a total of 355 alcohol-dependent patients: a multi center study sample (n=149) and a validation control sample (n=206). Neither an advantage of the score calculation rule nor the necessity of including items regarding alcohol consumption could be demonstrated. The exclusion of consumption items lead to a clear, stable 2-factor structure with a maximum stability (.81-.91). Retest-reliability ranged from r(tt)=.73 to r(tt)=.76 at an average time interval of 5 weeks. Concerning stability (.68-.81) and reliability (r(tt)=.76), the short version turned out to be equivalent. The short version of the OCDS seems to be sufficient. If different effects on cognitive and behavioral levels are expected, the 12-item version without the quantity items should be applied.

Functional Social Support within a Medical Supervised Outpatient Treatment Program

Background: This study examined functional social support (FSS) and its impact on treatment outcome in alcohol-dependent outpatients treated with supervised disulfiram. Method: FSS was assessed cross-sectionally in 46 severe alcohol-dependent patients participating in a close-meshed biopsychosocial treatment program. The FSS was measured with the Medical Outcome Study Social Support Survey. Results: We found significantly higher FSS levels in patients with a current partnership. No significant influence was found of the FSS on days until relapse and retention time. However, FSS was positively correlated with cumulative abstinence. In comparison with another patient sample, it can be shown that the patients of the close-meshed biopsychosocial treatment program seemed to perceive more FSS, presumably through the higher frequency of the outpatient treatment contacts. Conclusion: High FSS is associated with a current partnership and with a higher cumulative time of abstinence through close professional supervision. A better understanding of the underlying mechanisms of social relationships in alcohol-dependent patients would probably help to improve treatment outcome in the future.

Disulfiram, an Option for the Treatment of Pathological Gambling?

AIM Pathological gambling and comorbid alcohol dependence often occur in combination. Disulfiram is one of the proven drugs for alcohol dependence. In addition to its inhibiting acetaldehyde dehydrogenase, disulfiram inhibits dopamine beta-hydroxylase and may thereby increase dopamine and decrease norepinephrine cerebral concentrations. Because there may be common neurochemical substrates and neuronal circuits for pathological gambling and addiction, we wished to explore the effect of disulfiram in gambling. METHOD We describe the outcome of a patient with alcohol dependence and pathological gambling treated with disulfiram D. RESULTS During treatment with disulfiram, the patient reported that his desire to gamble disappeared entirely. Follow-up indicated that he has not gambled for >12 months. CONCLUSIONS Although uncontrolled case observations should be interpreted with caution, disulfiram deserves further investigation in pathological gambling.