Background: The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine. Recently, acute highfrequency 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.

The study suggests a gene-environment interaction whereby biological determinants of attachment disorganization are moderated by social experiences. Different pathways of the development of attachment disorganization are discussed based on a bio-behavioral model of development.

Genetic variations in NR2A have the greatest relevance for human alcohol dependence among the glutamatergic genes selected for their known alteration of alcohol effects in animal models.

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.

Abstract AbstractAIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection. METHODS:CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls. Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined. RESULTS:The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading. CONCLUSION:Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.