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Biomedical subjects

Norbert Wodarz

Publications and source records attributed to Norbert Wodarz.

At least 19 recordsLinked to original sources

A functional polymorphism in the promoter region of the monoamine oxidase A gene is associated with the cigarette smoking quantity in alcohol-dependent heavy smokers.

Tobacco smoking represents a leading cause of morbidity and mortality with a strong dose-response relation between the amount of smoking and the risks of tobacco-related diseases and death. The quantity that is smoked is determined predominantly by genetic factors. The present study examined whether there is an association between the quantity of cigarettes smoked and length variation of a functional 30-bp repeat polymorphism in the promoter region of the monoamine oxidase A (MAO-A) gene. The number of 30-bp repeats, which is associated with enzyme activity was assessed in 121 Caucasian men suffering from both alcohol and tobacco dependence. Analysis revealed that the highly active long allele (4 repeat) is associated with a significantly greater amount of cigarette smoking in comparison with the less active short allele (3 repeat). In a logistic regression model (dichotomized), smoking quantity was significantly predicted by MAO-A genotype while no other variable (age, height, body weight, frequency of smoking, quantity and frequency of alcohol consumption) met the significance level. Since tobacco smoke is a potent inhibitor of MAO-A, this result could be regarded as a genotype-related dosage effect. Taken together, in alcohol-dependent heavily smoking men there is evidence for a MAO-A gene-associated effect on the quantity that is smoked as reflected by the daily number of cigarettes consumed.

Alcohol Drinking↗

No association of dopamine receptor sensitivity in vivo with genetic predisposition for alcoholism and DRD2/DRD3 gene polymorphisms in alcohol dependence.

This study sought to examine dopamine receptor sensitivity among alcoholics in vivo and to explore whether this sensitivity might be associated with functional variations of dopamine D2 (DRD2) and D3 (DRD3) receptor genes along with a genetic predisposition for alcoholism as reflected by an alcohol-dependent first-degree relative. We analyzed the -141C Ins/Del polymorphism in the promoter region of the DRD2 gene and the Ser9Gly (BalI) polymorphism in exon 1 of the DRD3 gene in 74 alcohol-dependent Caucasian men with or without genetic predisposition for alcoholism. In vivo dopamine receptor sensitivity was assessed by measuring apomorphine-induced growth hormone release. A three-way analysis of variance revealed no significant effects of DRD2, DRD3 genotypes and genetic predisposition on dopamine receptor sensitivity. Given the explorative and preliminary character of this investigation, we cannot provide evidence that in alcohol-dependent Caucasian men a genetic predisposition for alcoholism along with functional variants of the DRD2 and DRD3 genes are associated with differences in dopamine receptor sensitivity.

Adult↗

Association of the -141C Del variant of the dopamine D2 receptor (DRD2) with positive family history and suicidality in German alcoholics.

Several lines of evidence indicate an involvement of the dopaminergic system in alcoholism, withdrawal, suicidality, and attention-deficit hyperactivity disorder (ADHD). The functionally relevant -141C Ins/Del polymorphism located upstream to exon 1 in the 5'-region of the dopamine D2 receptor (DRD2) gene might be an interesting candidate gene. We investigated a sample of 1,126 well-characterized, primary chronic alcoholics of German descent according to a phenotype-genotype strategy, i.e., alcoholics suffering from severe withdrawal complications such as seizure or delirium, family history positive (FH+) alcoholics, alcoholics with an antisocial personality disorder (ASPD), alcoholics with an ADHD, and type 1 or type 2 alcoholics according to Cloninger's typology. Compared to the control subjects, there was a significant excess of the -141C Del allele in alcoholics with a paternal and grandpaternal history of alcoholism and in alcoholic subgroups with suicidality or without a history of withdrawal symptoms. There were no significant differences in allele frequency between the entire group or subgroups of alcoholics and healthy controls. Therefore, the -141C Del variant of the DRD2 might be a protective factor against the development of withdrawal symptoms. However, it might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal and grandpaternal history of alcoholism and it might contribute to the substantially higher likelihood of suicide in alcoholics.

Alcoholism↗

[Outcome of a substitution therapy program in an outpatient treatment setting of a psychiatric hospital].

We look at 42 opiate addicts being in substitution therapy at a certain date (24.9.2003) in an outpatient treatment setting of a psychiatric hospital. Treatment outcome is described with amount of take home, reduced delinquency, increased social reintegration as well as pharmacological treatment. 25 men and 17 women, age from 20 to 49 (29) have been in our treatment between 1 to 52 months (29). 20 of them (48 %) got an additional psychiatric medication, mostly antidepressants (42 %) but also neuroleptics (9,5 %). 21 patients had a drug free urine test (including cannabis) during the last month and could take their opiate medication at home. Necessity of support by social security declines from 25 % before to 16 % in substitution treatment. Also the need of unemployment benefit could be reduced from 36 % before to 26 % in treatment. Full time jobs increase from 31 % to 48 %, part time jobs from 3 % to 7 % in treatment.

Adult↗

[Use of cigarettes, alcohol and drugs by adolescents--a questionnaire survey among 9th grade students].

INTRODUCTION: For the planning of further substance abuse prevention programs it is necessary to obtain data about the patterns of region-specific substance use in adolescents. METHOD: In 2002 a questionnaire survey on substance use among the 9 (th) graders of all school types in the city and in the county of Regensburg was carried out (mean age 15,3 years, N = 1580). RESULTS: The first substance ever used by adolescents are cigarettes, starting at an average age of 12.2 years. 30 % of the students are current daily smokers with 43 % fulfilling criteria of nicotine dependence. When used several times per week 53 % regard the use of spirits being very dangerous, whereas the same rate considers the danger of drinking wine or beer at the same frequency being rather small. The level of information about institutions offering help for substance abuse and dependence problems is being considered as poor or zero by 67 %. DISCUSSION: The primary prevention of smoking as early as possible should be a priority of school-based prevention programs. The study also reveals a deficit of information on substances and institutions offering help for substance abuse and dependence problems which should be faced in school lessons.

Adolescent↗

[Attachment styles in German alcoholics with or without attention-deficit hyperactivity disorder (ADHD)].

INTRODUCTION: Attachment theory yields empirical constructs for development of human self, personality and cognition. Insecure attachment strategies were associated with various psychiatric disorders. METHOD: We investigated distribution of attachment styles in 368 adult alcoholics of German descent with or without persistent symptoms of attention-deficit hyperactivity disorder (ADHD) and in 402 healthy individuals. RESULT: Insecure attachment styles were significantly overrepresented compared to healthy controls. The subgroup of alcoholics with ADHD showed significantly more frequent enmeshed (74.1 %), the subgroup of alcoholics without persistent ADH-associated symptoms showed more frequent dismissing (35 %) attachment strategies. CONCLUSION: In our sample, insecure attachment styles are associated with alcoholism. The subgroup of alcoholics with persistent ADHD shows a specific attachment behavior that could contribute to different therapy response or to early onset or severity of alcoholism.

Adult↗

[ADHD and alcohol dependence: a common genetic predisposition?].

INTRODUCTION: Nearly 50 % of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood show a comorbid substance use disorder. Both, ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. METHOD: We investigated phenotype and 5-HTT/5-HT2c allelic characteristics in 314 alcoholics of German descent. RESULT: 21 % of the alcoholics fulfilled DSM-IV-criteria of ADHD with ongoing symptoms in adulthood. There was no significant difference in 5-HTT- or 5-HT2c-allele distribution between alcoholics and matched controls or between alcoholics with or without ADHD. CONCLUSION: In our sample the functional relevant 5-HTT-promoter and the 5-HT2c-receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

Adolescent↗

[Attention-deficit hyperactivity disorder and alcohol dependence: a risk constellation].

INTRODUCTION: The estimated prevalence for attention-deficit hyperactivity disorder (ADHD) in adulthood is 2 - 6 %. Patients with a substance use disorder met the criteria for ADHD between 30 and 50 %. ADHD and conduct disorders are discussed to increase risk of developing substance abuse and increase severity of disorder. METHOD: We compared epidemiological and clinical characteristics and comorbidity in subgroups of 314 adult alcoholics of German descent with or without persistent symptoms of attention-deficit hyperactivity disorder (ADHD). Aim of the study was to identify specific pathophysiological mechanisms that could contribute to vulnerability, severity or complication of alcohol dependence. RESULTS: 21.3 % of the alcoholics fulfilled DSM-IV-criteria of ADHD with ongoing symptoms in adulthood and had a Wender-Utah-Rating-Scale score > 90. Subgroup of alcoholics with ADHD were significantly younger at age of onset of alcoholism (24 years versus 30 years), had a significantly higher daily alcohol intake (253 g versus 196 g EtOH), had significantly more social stress, lifetime experiences in court proceedings against them (11 versus 2 %) and suicidal ideation (25 versus 11 %). In the subgroup of alcoholics with ADHD 51 % fulfilled criteria of antisocial personality disorder. The early onset of alcoholism was most pronounced in this subgroup. CONCLUSION: In our sample, persistence of ADHD symptoms from childhood into adulthood and antisocial personality disorder contributes to vulnerability and morbidity of alcohol dependence with early onset and greater severity of disorder.

Adult↗

Serotonin transporter gene polymorphism and personality traits in primary alcohol dependence.

We tested the hypothesis of an association between the serotonin transporter (5-HTT) gene regulatory region polymorphism and the Temperament and Character Inventory (TCI) personality dimension of Harm Avoidance. For the study, 124 subjects seeking inpatient treatment for primary alcohol dependence were grouped by their 5-HTT genotype and assessed with the TCI. Genotypes differed statistically significantly in Harm Avoidance but not in any other personality trait. This gives support to the hypothesis that the TCI temperament Harm Avoidance is associated with serotonergic neurotransmission in primary alcohol dependence.

Adolescent↗

[Repetitiv Transcranial Magnetic Stimulation in Nicotine Dependence]

70 - 80 % of regular smokers fulfill the ICD-10-criteria of dependence. In Germany, approximately 120 000 deaths per year are caused by tobacco-associated diseases. In contrast, therapeutic interventions, such as nicotine substitution or bupropione, yield poor abstinence rates of 30 % after 12 months, at best. In animal experiments, repetitive transcranial magnetic stimulation (rTMS) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system. This pilot study should evaluate, if rTMS could modulate subjective craving for tobacco, which quite often leads to relapse to smoking. Therefore, 11 tobacco-dependent cigarette smokers were randomly assigned to a course of verum- and placebo-rTMS on consecutive days. Craving, as measured by a visual analogue scale, is significantly decreased after Verumstimulation compared to placebostimulation intra-individually. This encourages further studies to clarify, if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits.

Journal Article↗

[Chronic Alcoholics with Multiple Impairments]

To improve reliability of diagnosis of a specific subgroup of chronic alcoholics with multiple impairments (CMA), operational criteria have been proposed. To evaluate usability and sensitivity vs. specifity, all in-patients fulfilling ICD-10 criteria of alcohol dependence were screened on two randomly chosen dates. Two clinically "extreme" groups were extracted: patients in a 8-week short-term residential treatment vs. patients in a residential program specifically designed for chronic alcoholics with severe somatic, psychic and/or social consequences. More quantitative operational criteria, such as "treatment experience" and "consumptive behaviour" revealed much lower discriminative power than more qualitative criteria, such as "comorbidity" and "social and legal status". Substantially revised and simplified operational criteria exhibited comparable sensitivity and specifity for the classification of chronic alcoholics with multiple impairments (CMA).

Journal Article↗

[Relapse Prevention Program in German Alcoholics]

Relapse prevention plays an important role in the treatment of alcoholics. Positive predictors are high self-efficacy and confidence in high-risk situations, positive outcome expectancies, sufficient coping-skills and low craving. We examined 64 primary German alcoholics. Each person met the criteria of alcohol dependence of DSM-IV and ICD-10. Subjects were included in an in-patient 4-step relapse prevention program. This manual-guided group psychotherapy is based on cognitive-behavioral approach focused on high-risk situations, phases of relapse, stress/relax and resources. Craving before and after treatment did not differ, so that using this kind of relapse prevention training might be suitable in both in- and out-patient programs. High values for insight, optimism, self-efficacy and confidence in high-risk situations might enhance individual coping-skills to balance patient's lifestyle focussing on an abstinent way of life.

Journal Article↗

[Neuroleptic Treatment of Opiate Addicts with a Comorbid Schizophrenia in a Methadone Maintenance Program]

Methadon maintenance therapy with opiate addicts who suffer from a comorbid schizophrenia in an outpatient treatment setting of a psychiatric hospital is described. We examined five patients looking for periods of inpatient treatment, drug free urine tests, social integration and illegal activities before and after neuroleptic treatment. In comparison with standard neuroleptics patients show under the therapy with atypical neuroleptics better outcome in drug urine tests especially concerning cannabis and benzodiazepines. According to these findings, the best improvements seem to occur with a combination of methadone and clozapine.

Journal Article↗

Comorbidity of alcohol dependence with attention-deficit hyperactivity disorder: differences in phenotype with increased severity of the substance disorder, but not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor).

BACKGROUND: Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities. METHODS: We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent. RESULTS: There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively. CONCLUSIONS: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence.

Adolescent↗

High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking.

BACKGROUND: The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine. Recently, acute high-frequency repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions has been shown to efficiently modulate the mesostriatal and mesolimbic dopaminergic system in both animals and humans. For this reason, we investigated whether high-frequency rTMS would be able to influence nicotine-related behavior by studying rTMS effects on craving and cigarette smoking. METHOD: Fourteen treatment-seeking smokers were included in a double-blind crossover trial, conducted in 2002, comparing single days of active versus sham stimulation. Outcome measures were rTMS effects on number of cigarettes smoked during an ad libitum smoking period and effects on craving after a period of acute abstinence. RESULTS: High-frequency (20-Hz) rTMS of left dorsolateral prefrontal cortex reduced cigarette smoking significantly (p <.01) in an active stimulation compared with sham stimulation. Levels of craving did not change significantly. CONCLUSION: High-frequency rTMS may be useful for treatment in smoking cessation.

Adult↗

[Chronic alcoholic patients with multiple comorbidity. Community outpatient evaluation of a recommendation for operationalized diagnosis and alternative models].

To improve reliability of diagnosis of a specific subgroup of chronic alcoholics with multiple impairments (CMA), operational criteria have been proposed. To evaluate usability and sensitivity vs. specificity, all in-patients fulfilling ICD-10 criteria of alcohol dependence were screened on two randomly chosen dates. Two clinically "extreme" groups were extracted: patients in a 8-week short-term residential treatment vs. patients in a residential program specifically designed for chronic alcoholics with severe somatic, psychic and/or social consequences. More quantitative operational criteria, such as "treatment experience" and "consumptive behaviour" revealed much lower discriminative power than more qualitative criteria, such as "comorbidity" and "social and legal status". Substantially revised and simplified operational criteria exhibited comparable sensitivity and specificity for the classification of chronic alcoholics with multiple impairments (CMA).

Alcoholism↗

[Neuroleptic therapy of comorbid narcotic dependent patients in ambulatory methadone maintenance].

Methadon maintenance therapy with opiate addicts who suffer from a comorbid schizophrenia in an outpatient treatment setting of a psychiatric hospital is described. We examined five patients looking for periods of inpatient treatment, drug free urine tests, social integration and illegal activities before and after neuroleptic treatment. In comparison with standard neuroleptics patients show under the therapy with atypical neuroleptics better outcome in drug urine tests especially concerning cannabis and benzodiazepines. According to these findings, the best improvements seem to occur with a combination of methadone and clozapine.

Adult↗

[Relapse prevention group for alcohol dependent patients].

Relapse prevention plays an important role in the treatment of alcoholics. Positive predictors are high self-efficacy and confidence in high-risk situations, positive outcome expectancies, sufficient coping-skills and low craving. We examined 64 primary German alcoholics. Each person met the criteria of alcohol dependence of DSM-IV and ICD-10. Subjects were included in an in-patient 4-step relapse prevention program. This manual-guided group psychotherapy is based on cognitive-behavioral approach focused on high-risk situations, phases of relapse, stress/relax and resources. Craving before and after treatment did not differ, so that using this kind of relapse prevention training might be suitable in both in- and out-patient programs. High values for insight, optimism, self-efficacy and confidence in high-risk situations might enhance individual coping-skills to balance patient's lifestyle focussing on an abstinent way of life.

Adaptation, Psychological↗