Stimulus-induced craving and startle potentiation in abstinent alcoholics and controls.

Abstinent alcoholics often deny craving for alcohol but still show a high level of relapse. The eyeblink response to startling noise was used as an indicator of the emotional response to alcohol-related, positive, negative and neutral visual stimuli in abstinent alcoholics, social drinkers and rarely drinking controls. The cognitive evaluation of the stimuli was assessed by ratings of subjective craving, valence and arousal. The startle response of the alcoholics to alcohol-related stimuli was significantly inhibited despite an aversive overt stimulus-evaluation. These findings indicate that alcohol-related stimuli may have appetitive incentive salience for alcoholics in spite of verbal reports of craving and valence to the opposite.

[Acute delusional psychosis and neuroleptic malignant syndrome after emigration of a Russian German patient]. / Akute wahnhafte Psychose und malignes neuroleptisches Syndrom nach Emigration bei einem Russlanddeutschen.

Emigration is often followed by psychic disorders. The special issue of Germans from the GUS-States immigrating to Germany is presented. The modus of paranoid reaction is discussed along the biography and the criteria of ICD 10. The acute paranoid psychosis was complicated by a neuroleptic malignant syndrome.

Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium.

Hereditary factors confer susceptibility to alcohol dependence. Alcohol mediates its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine system. The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission suggests that variants of the dopamine transporter gene (DAT1) might contribute to individual differences in vulnerability to addictive behavior. Our population-based association study investigated whether variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics and clinically more homogeneous subgroups formed by: positive family history, early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1 and 2 alcoholics. Analyzing a VNTR polymorphism in the 3' untranslated region of DAT1, we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying withdrawal seizures or delirium, compared with 93 ethnically matched nonalcoholic controls (p = 0.003; OR = 2.44; 95% confidence interval: 1.35-4.43). Our data provide evidence that a major genetic determinant of DAT1 influences vulnerability to severe alcohol withdrawal symptoms.

Antisocial tendencies in alcohol-dependent men and their relation to harman, salsolinol and dopamine.

Plasma dopamine, ß-carbolines (norharman, harman) and isoquinolines ((R)- and (S)-salsolinol) were examined for their relationship to antisocial tendencies in 138 drinking men with an alcohol dependence syndrome according to ICD-10 criteria. Antisociality was assessed according to the following criteria: delinquency, involvement in fist-fights and homelessness. The personality structure was documented by the Tridimensional Personality Questionnaire of Cloninger. An early age of onset of alcohol dependence and a high degree of 'novelty seeking' were associated with antisocial tendencies. Of the ß-carbolines and isoquinolines, harman and (S)-salsolinol were significantly decreased among antisocial alcoholics. Norharman, (R)-salsolinol and dopamine were not associated with antisocial personality. The contribution of endogenous alkaloids to the biological characterization of antisocial tendencies in alcoholics is described.

[Alcohol dependence in homeless men. Incidence, development and determinants]. / Alkoholabhängigkeit bei männlichen Wohnungslosen. Häufigkeit, Ausprägung und Determinanten.

Against the background of the complex relationship of alcoholism and homelessness, we investigated the question of whether homeless alcoholics and those with homes differed regarding biographical and clinical variables. Therefore, 49 of 72 (68.1%) homeless male visitors to a city kitchen in the center of Berlin, who had fulfilled the ICD-10 criteria for the alcohol-dependence syndrome, were compared with 141 outpatients of the addiction research unit of the Department of Psychiatry of the Free University of Berlin. It was found that homeless alcoholics had more psychosocial disadvantages than other alcoholics. They had been raised more frequently in families with an alcoholic father or mother and a higher number of children. The level of education and job qualification was lower in the homeless alcoholics. Early homelessness was predicted by a lack of sexual behavior (no partnership experienced) and a family history of alcoholism. In the interview, homeless alcoholics reported fewer symptoms of alcohol-dependence syndrome than other alcoholics; however, the first symptoms had been experienced earlier. Alcohol-related somatic and psychological consequences were reported more frequently in alcoholics with homes, whereas social problems were more common in the homeless subjects. The results are discussed in the light of methodological limitations and other reports on the topic.

No association of the structural dopamine D2 receptor (DRD2) variant 311Cys with alcoholism.

The human dopamine D2 receptor (DRD2) has been implied in the vulnerability for alcoholism and/or the modification of its severity. This is supported through animal experimental and pharmacological data. We analyzed the DRD2 311Ser/Cys polymorphism in 312 German alcoholics and 131 ethnically matched controls to investigate the association of genetic DRD2 variants with alcoholism or clinical characteristics of homogeneous subgroups of alcoholics. We observed no association between the 311Cys variant and alcoholism, and none of the clinical characteristics evaluated was significantly associated with 311Cys. The allele frequencies of the 311Cys variant were 0.026 and 0.031 in the alcoholics and controls, respectively. These are the highest reported 311Cys frequencies in Caucasians. The DRD2 TaqI A1/A2 restriction fragment length polymorphism was analyzed simultaneously in our samples. In most cases, the 311Cys allele is associated with the TaqI A2-allele. Data do not suggest a clinical relevance of the 311Cys variant in alcoholism. However, the relevance of this variant in other diseases or the existence of other DRD2 variants with altered receptor function or expression cannot be excluded.

Reduced dopaminergic function in alcoholics is related to severe dependence.

With a view to the role of dopamine (DA) systems in reward processes and considering recent studies linking specific alleles at the DA-D2 receptor gene locus with alcoholism (especially with severe types) dopaminergic functions were evaluated in 49 alcoholics using growth hormone (GH) response to DA receptor agonist apomorphine (0.01 mg/kg subcutaneously). neuroendocrine testing was performed (during intoxication) at the time of admission to an inpatient alcohol treatment program and was repeated 7 days later (in a postintoxicated state). Patients underwent clinical examination, detoxification treatment and a subsequent rehabilitation program for abstinence including follow-up evaluation of outcome for 6 months. A two-factor analysis of variance (ANOVA) revealed a significant change of GH response (peak values corrected for baseline) over time (between intoxication and postintoxication; p < 0.001) and between abstainers and relapsers (p = 0.032). Relapse was also associated with paternal alcoholism, early onset of disease, and a more complete dependence syndrome and cerebellar atrophy. Standardized canonical discriminant coefficient was highest for reduced GH response compared to other relapse predictors in the model used. It is concluded that reduced GH response to dopaminergic stimulation corresponds to a progressed stage or syndrome of severe alcohol dependence; however, if reduced, dopaminergic function is one cause or consequence of addiction in this particular subgroup of patients that remains to be elucidated.

Dopamine D1, D2 and D3 receptor genes in alcohol dependence.

Hereditary factors play a substantial role in the etiology of alcohol dependence. Alcohol mediates its reinforcing effects by an activation of the mesolimbic dopamine system. These findings suggest that the genes encoding the dopamine receptor (DR) subtypes represent high-ranking candidates for susceptibility genes to addictive disorders. Our present population-based association study investigated whether sequence variants of the dopamine D1, D2 and D3 receptor genes confer susceptibility to alcohol dependence in 278 alcoholics, and clinically more homogeneous subgroups ascertained through positive family history, early age at onset, delirium, withdrawal seizures and antisocial tendencies. No evidence for an allelic association was found for the PCR-based TaqA RFLP fo the DRD2 gene and a Bsp1286I RFLP of the DRD1 gene. Without correction for multiple testing, we found a significantly increased allele frequency of a common DRD3 gene variant expressing a serine at position 9 in the extracellular N-terminal part of the receptor protein in 55 alcohol-dependent individuals with delirium (chi 2 = 4.1, df = 1, p = 0.042). Further studies have to examine whether this amino acid substitution or a nearby mutation confers genetic susceptibility to at least a subgroup of alcohol-dependent individuals with delirium.