Advances in alcoholism research in Germany.
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Alcohol Withdrawal Delirium↗
Biomedical subjects
H G Weijers
Publications and source records attributed to H G Weijers.
Cu, Zn- and Mn-superoxide dismutase levels in brains of patients with schizophrenic psychosis.
Impaired oxidative stress defense has been reported in blood of both drug-naïve and antipsychotic-treated patients suffering from schizophrenic psychosis, indicating the involvement of free radical metabolism in the pathogenetic processes of schizophrenia. In this study, the concentrations of two isoenzymes of superoxide dismutase (SOD), Cu, Zn- and MnSOD, were determined with ELISA in various cortical (frontal, parietal, temporal and occipital cortex) and subcortical areas (putamen, caudate nucleus, thalamus, and substantia innominata) of post-mortem brain tissue from patients diagnosed with a schizophrenia spectrum disorder and compared with those of controls. Post-mortem brain tissue from individuals without neuropsychiatric disorders served for control. Cu, Zn- and MnSOD levels were significantly increased in frontal cortex and substantia innominata of the index group, respectively. In all other areas both types of SOD remained virtually unchanged. Detection of SOD changes in the brain supports previous reports of alterations of antioxidant indices in blood cells of patients with schizophrenia and suggests a specific neuroanatomical distribution pattern of oxidative stress processes possibly related to the pathophysiology of schizophrenia.
Adult↗
The candidate gene approach in alcoholism: are there gender-specific differences?
It is well established that genetic factors play a major role in the development of alcoholism in both sexes. Several twin studies demonstrated a nearly equally high magnitude of genetic influence for men and women. However, the genetic sources of vulnerability are supposed to only partially overlap in men and women. Therefore, we evaluated the gender-specific effects of two single nucleotide polymorphisms affecting dopaminergic neurotransmission (dopamine D2 receptor: -141C Ins/Del polymorphism; Dopamine D3 receptor: Bal I) in our large sample of primary alcoholics. Only a gender-specific analysis of subgroups with a putatively high genetic load, e.g., family-history-positive or presence of severe withdrawal complications, revealed significant differences in allele-/genotype-frequency. Our results demonstrate that a varying sex distribution in the samples investigated might contribute to the heterogeneous results reported in association studies for candidate genes in alcoholism and, therefore, should be taken into account in future studies.
Adult↗
[Wender Utah rating scale. The short-version for the assessment of the attention-deficit hyperactivity disorder in adults].
This work presents a statistical analysis of the German version of the Wender Utah rating scale (WURS) for the retrospective diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults. Data were obtained from 703 subjects. Item selection according to item-total correlation scores, frequency, and plausibility led to a short version of the scale that includes 21 items with item-total correlations from 0.19 to 0.61. Retest reliability of the WURS-k was r=0.9.
Adolescent↗
Neuroendocrine responses to fenfluramine and its relationship to personality in alcoholism.
This study investigates the relationship between personality and serotonergic reactivity in alcohol dependence. Personality characteristics were assessed according to the Temperament and Character model of Cloninger, the five-factor model of McCrae and Costa, Zuckerman's Sensation Seeking as well as Eysenck's impulsiveness/venturesomeness. Placebo-controlled prolactin response to the serotonin (5-HT) reuptake inhibitor/releaser fenfluramine served as an indicator for the reactivity of serotonergic neurotransmission. Forty abstinent alcohol-dependent men were subdivided into high and low prolactin responders according to their level of neuroendocrine response. High responders were characterized by decreased harm avoidance while their extraversion and venturesomeness scores were increased in comparison to low responders. The data demonstrates that harm avoidance on the one hand and extraversion/venturesomeness on the other are inversely correlated to serotonergic neurotransmission. These results support a specific relationship between personality traits and the serotonergic system.
Adult↗
Genome polymorphism and alcoholism.
Different gene variants have been identified as risk or protective factors in alcoholism. The genes coding for dopamine receptors, serotonin transporters, and dehydrogenases represent susceptibility loci for addictive behaviour. However, alcoholism represents a complex psychiatric symptomatology which is caused by multiple factors, both genetic and environmental. Furthermore, there are probably different subtypes of alcoholism each with a distinct pathophysiology, and thus a different genetic background. Genetic research can help to identify such subtypes, which may require different therapeutic approaches. However, gene polymorphisms are not only responsible for a predisposition to alcoholism, but also for personality traits which influence the likelihood of developing addictive behaviour. Moreover, genetic polymorphisms are probably involved in the way an individual responds to treatment. Also, the severity of secondary diseases resulting from chronic alcohol uptake may depend on the genetic makeup of an individual. New treatment strategies focusing on genes contributing towards drug and alcohol dependence (such as gene therapy) are already under examination in animal models. However, further research is required before these developments will considerably change today's clinical handling of alcoholism.
Alcoholism↗
Event-related potentials and cue-reactivity in alcoholism.
BACKGROUND: Relapse is a major problem in the treatment of addictive behaviors. Conditioning models of alcohol addiction suggest that stimuli associated with previous drug use (cues) may initiate relapse in a definite group of alcoholics. Event-related potentials (ERPs) might be useful to reveal the brain functional substrates of cue-reactivity. METHODS: In a preliminary investigation, 11 alcohol-dependent patients who did not take part in the electrophysiological study completed a structured interview to rate 80 words as to the degree of relatedness to alcohol. Based on these results, cue-reactivity for 15 alcohol-related and 15 unrelated word cues, each repeated eight times, was investigated in 19 alcohol-dependent men (44.2 +/- 8.5 years) and 19 healthy control men (42.5 +/- 12.5 years). RESULTS: A cue-reactivity that consisted of significantly higher amplitudes in the ERPs after alcohol-related words compared with unrelated words was found in alcohol-dependent patients, but not in controls, at the electrode location Pz [F(1,36) = 5.2,p < 0.05]. CONCLUSIONS: Consistent with the hypothesis, only alcohol-dependent patients were characterized by signs of increased cerebral activity associated with alcohol-related compared with unrelated cues. Therefore, the results support the concept of cue-reactivity in alcoholism based on a neurobiological measurement. Future investigations will show whether this cue-reactivity can be applied to assess the risk of relapse in individual alcohol-dependent patients.
Adult↗
[Temperament- and character traits as well as trait patterns in alcoholic men and controls].
This study is on the personality of alcoholics, an empirical investigation based on Cloninger's biopsychological temperament- and character-traits. His Temperament and Character Inventory (TCI) was applied to 94 detoxified men suffering from primary alcohol dependence as well as to controls matched for sex and sociodemographic data. The following questions were the matter of interest: (1) Do alcoholics and controls differ in their personality as reflected by the TCI and (2) are there indicators based on personality with potential relevance for differential therapies? A multiple univariate statistical comparison yielded significant differences between alcoholics and controls on only 2 subscales (Sentimentality, Resourcefulness). A multivariate analysis of the TCI temperament traits using two-sample configural frequency analysis revealed no statistically significant difference between the two groups. Temperament patterns associated with Cloninger's Type-I/Type-II alcoholics could not be demonstrated. Analyzing the temperament and character traits of the alcohol dependent subjects with a log-linear model revealed two bivariate temperament-/character classifications on the scales "Harm Avoidance" and "Self-Directedness" as well as "Reward Dependence" and "Self Transcendence"-both making it possible to define subgroups which may be relevant for different therapeutical approaches. Taken together, the results of this study suggest that it may be useful to closer investigate the personality of alcoholics even if it is not principally different from that of control subjects.
Adult↗
Dopamine D3 receptor gene polymorphism and alcohol dependence: relation to personality rating.
Hereditary dopaminergic mechanisms have been implicated in the aetiology of alcoholism. For this study, the distribution of a dopamine D3 receptor gene polymorphism (Ball) has been investigated in patients suffering from alcohol dependence, and compared with non-dependent controls. The allele A1 occurred significantly more frequently among patients compared to controls. Patients with the genotype A1/A2 showed significantly higher novelty seeking (NS) scores in the tridimensional personality questionnaire (TPQ) than patients with the genotype A1/A1. The distribution of patients with high and low NS scores in heterozygotes (A1/A2) did not follow a random distribution. There were significantly more individuals with higher NS scores, and fewer individuals with lower NS scores than expected. The results of this study support the hypothesis of a genetically determined involvement of the dopaminergic system in alcohol dependence. This is probably related to the modulation of personality traits. The observed effects are relatively small, but statistically significant. Thus, the genetics of the dopaminergic neurotransmitter system alone cannot explain the aetiopathogenesis of alcoholism.
Adult↗
Ritanserin in relapse prevention in abstinent alcoholics: results from a placebo-controlled double-blind international multicenter trial. Ritanserin in Alcoholism Work Group.
Ritanserin, a long-acting specific 5-HT2 receptor antagonist, revealed promising effects on alcohol intake behavior in both animal and preliminary human studies. To test its effectiveness in alcohol dependence this phase III clinical trial was initiated. In a placebo-controlled, randomized, double-blind international multicenter study 493 patients with moderate or severe alcohol dependence (DSM-III-R) were treated with three doses of ritanserin 2.5 mg/day (n = 122), 5 mg/day (n = 123), 10 mg/day (n = 126), or placebo (n = 122) over a period of 6 months. Ritanserin was well tolerated. The most frequent adverse experiences were headache and insomnia. A small increase in weight in the ritanserin-treated patients was observed. There were no significant differences between any dose of ritanserin and placebo in the relapse-rate, the time to relapse, craving for alcohol, or quantity and frequency of drinking after relapse. So far, neither ritanserin nor any other serotonergic medication has shown its specific effectiveness in relapse prevention in alcohol dependence.
Adult↗
Growth hormone response to placebo, apomorphine and growth hormone releasing hormone in abstinent alcoholics and control subjects.
Abstinent alcoholics and control subjects were challenged with placebo (saline), growth hormone releasing hormone (GHRH) and apomorphine (APO). While both groups did not differ in their growth hormone response (HGH) to placebo and GHRH, the alcoholics revealed a significant lower HGH response to dopamine receptor stimulation with APO. These findings provide no evidence that in abstinent alcoholics HGH blunting after dopamine receptor stimulation could be related to an alteration at the pituitary level but they give neuroendocrinological support to the hypothesis of a lower dopamine receptor sensitivity in abstinent alcoholics.
Adult↗
Locomotor activity and defecation of rats observed alone and in pairs in repeated open-field sessions.
Several experiments with independent groups have shown social effects on open-field defecation and locomotor activity in male rats. In this experiment these social effects were studied with a different methodological approach, namely, with repeated measurements. One group of 8 animals was tested always alone in an open field over 10 trials on successive days. The second group of 16 animals was also tested alone on Days 1 to 4 and on Day 9, while they were placed in the open field with a conspecific on Days 5 to 8 and again on Day 10. There was markedly reduced defecation and enhanced locomotion with the conspecific present, while with the absence of the conspecific on Day 9 the scores again reached the level of the rats always tested alone. Therefore, the social effects on defecation and locomotion are very robust phenomena which can also be shown with dependent measurements.
Animals↗
Scanning behavior of rats during eating under stressful noise.
Behavioral ecological theories postulate that threatening environments should increase eating speed and vigilance during feeding. In the present experiment, eating speed and scanning behavior during eating were measured in 36 rats in 5 consecutive test sessions under stressful noise (95 dB white noise, n = 18) and control conditions (60 dB, n = 18) after the animals had been habituated to the test environment. Intense noise induced an increase of scanning rate and eating speed. These effects are similar to those reported for novel and light environments.
Animals↗
Evidence for increased oxidative stress in alcohol-dependent patients provided by quantification of in vivo salicylate hydroxylation products.
The hypothesis of increased oxidative stress in alcohol-dependent patients postulates that altered free radical metabolism is involved in the various symptoms associated with this disease, including brain atrophy, peripheral polyneuropathy, alcoholic liver fibrinogenesis, and cancer. Using an in vivo assay for quantitation of hydroxyl radical (.OH) levels in peripheral blood, we detected increased values in patients suffering from alcohol dependence when compared with non-dependent control persons. The assay used in this study involves the injection of acetylsalicylic acid, which is metabolized in vivo by direct reaction with .OH to 2,3-dihydroxybenzoic acid (DHBA). The time curve for the concentration of the reaction product (2,3-DHBA), determined by high-performance liquid chromatography, thus estimates the .OH radical level in the peripheral blood of individuals undergoing this test. For the first time, we used the intravenous application of acetylsalicylic acid to avoid artifacts arising from differences in gastrointestinal resorption, known to be disturbed in alcoholism. The areas under the 2,3-DHBA time curves differed significantly (p < 0.05) between patients and controls (0.54 +/- 0.27 vs. 0.36 +/- 0.19 microM.h). This study presents further evidence for alterations in radical metabolism in vivo in patients suffering from alcohol dependence. The assay can also be used in further studies dealing with antioxidative treatment (radical scavengers) to evaluate the effectiveness of such therapy.
Adult↗
A null mutation allele in the CNTF gene and schizophrenic psychoses.
The maldevelopmental theory postulates disturbances in neural development as crucial factors in the aetiopathogenesis of schizophrenia. Neurotrophic factors, including ciliary neurotrophic factor (CNTF), play a central role in the regulation of such development. A mutation has been described for the CNTF gene, whereby subjects homozygous for the mutation lack CNTF. The polymerase chain reaction was used to amplify the CNTF gene region containing this mutation in whole blood genomic DNA. The mutation was detected by analysis of restriction fragment length polymorphisms. Patients suffering from schizophrenic psychosis (ICD-10 criteria) (51 from Würzburg, 83 from Barcelona), and healthy controls (62 from Würzburg, 50 from Barcelona) were investigated. In the Würzburg group, the frequency of subjects homozygous or heterozygous for the mutation was significantly higher among schizophrenic patients than in controls. However, no difference could be detected in the Spanish sample; the possible reasons for the different allele distribution in the two patient groups is discussed. It is concluded that the CNTF null mutation may be relevant to the aetiopathogenesis of schizophrenia in some patients, but further work is required to identify specifically the patient group for which it is important.
Adult↗
Effects of stressful noise on eating and non-eating behavior in rats.
Eating and other behaviors were measured in 36 food-deprived rats on 15 consecutive days during 20 min test sessions. During training sessions 1 to 5 all animals were habituated to the test boxes with white noise of 55 dB intensity. For sessions 6 to 10 noise intensity was increased to 95 dB for the experimental rats and to 60 dB for the control rats. The food intake of experimental rats was lower for stress session 1. The duration of eating behavior was lower, and durations of exploring, grooming and resting behaviors were higher for all stress sessions for rats exposed to 95 dB white noise. Speed of eating behavior was higher for all stress sessions in the experimental group. Defecation rate of the experimental rats was higher for all stress sessions. On post-stress sessions 11 to 15 animals were again tested under the stimulus conditions of the training period (55 dB). No significant effects were observed for this period. The results are discussed with respect to models of "stress-induced" eating and behavioral ecology.
Animals↗
Event-related correlates of response suppression as indicators of novelty seeking in alcoholics.
Novelty Seeking including impulsive behaviour is a personality dimension which has been shown to be related to early-onset alcoholism and to high relapse rates. The cued Continuous Performance Test (CPT) is an experimental paradigm for active response control requiring a choice reaction between execution (Go) and inhibition (NoGo) of a prepared motor response. Metabolic functional methods have shown right frontal brain activation throughout the period of a CPT, and the spatial analysis of the associated event-related brain electrical (ERP) field potentials revealed that this right frontal activation was due to the NoGo subset of the task. The ERP fields allow distinction between the Go and NoGo conditions with one spatial parameter (NoGo-anteriorization) in single cases. and the magnitude of this parameter is thought to be related to inhibitory frontal lobe control. Twenty patients with severe alcohol dependence and 20 age- and sex-matched healthy controls were included in the study and investigated with a 21-channel electroencephalogram while performing a cued CPT. Consistent with previous studies, NoGo-anteriorization was present in every case in both groups. The ERP field differed between alcoholics and controls in the Go condition (P < 0.05) and NoGo-anteriorization in alcoholics was correlated inversely with Novelty Seeking in Cloninger's Temperament and Character Inventory (r= 0.67, P < 0.01). This indicates a reduced frontal lobe contribution during response control in alcoholics with impulsive behaviour and identifies a possible biological marker for the clinical evaluation of the risk of relapse in alcoholism.
Adult↗
The effects of ritanserin on mood, sleep, vigilance, clinical impression, and social functioning in alcohol-dependent individuals. Ritanserin in Alcoholism Work Group.
In an international double-blind placebo-controlled trial with 493 detoxified alcohol-dependent individuals, ritanserin, a specific 5-hydroxytryptamine, antagonist, was tested in three different dosages (2.5, 5, and 10 mg/day) against placebo over a period of 6 months. Data on changes in mood state, sleep quality, morning vigilance, clinical impression, and social functioning were analysed. None of the three dosages of ritanserin given revealed any significant effect against placebo on the above-mentioned parameters either at the end of treatment or upon relapse. Therefore, we conclude that patients suffering from alcohol dependence without concomitant psychiatric disorders do not benefit from additional treatment with (2.5, 5, or 10 mg/day) ritanserin.
Adult↗