Does the transcription factor AP-2β have an impact on the genetic and early environmental influence on ethanol consumption?

Genes involved in alcoholism have consensus sites for the transcription factor activator protein (TFAP) 2β. In the present study, we investigated TFAP-2β protein levels in the ethanol-preferring alko, alcohol (AA) and the ethanol-avoiding alko, non-alcohol (ANA) rat lines. Furthermore, basal and ethanol-induced TFAP-2β levels were examined in Wistar rats exposed to different early postnatal environments that are known to affect later ethanol consumption. Taken together, we found differences in brainstem TFAP-2β protein between the AA and ANA rats

ADHD and Disruptive behavior scores – associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents

<p>Abstract</p> <p>Background</p> <p>Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorder (DBD). We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B (MAO-B) activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats (MAO-A VNTR) and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region (5-HTT LPR).</p> <p>Methods</p> <p>A population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5-HTT genes.</p> <p>Results</p> <p>We found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder (ODD). In girls, there was also an association between the heterozygote long/short 5-HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5-HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder (CD). In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior.</p> <p>Conclusion</p> <p>Our study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.</p

Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-α therapy

Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-α (IFN-α). Animal studies showed that IFN-α administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H2O2 generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-α. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-α, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-α are unlikely to contribute to definite psychiatric disturbance

Serotonin, genetic variability, behaviour, and psychiatric disorders - a review

Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing, and development of the serotonergic neurons, during early brain development

Smoking as a product of gene–environment interaction

A strong hereditary influence on smoking has been demonstrated. As one of the candidate genes in relation to smoking, the serotonin transporter gene (5-HTTLPR) has been suggested, however with conflicting results. In recent studies, it has been shown that genotypic and environmental (G*E) factors interact in the shaping of a variety of phenotypic expressions. The objective of the present study was to investigate the interaction between a variation in the 5-HTTLPR and family environment in relation to smoking habits, nicotine dependence, and nicotine and cotinine levels in hair samples

COMT genotype and non-recovery after a whiplash injury in a Northern European population

Background: The COMT (Catechol-O-Methyl Transferase) gene may influence a person's vulnerability to develop long-term pain and some COMT single nucleotide polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many patients with whiplash-associated disorders (WADs) suffer from long-term pain and other related symptoms, but it is less known if genetic factors play a role in the recovery process. The primary aim of this study was to evaluate whether self-reported non-recovery, including pain, was related to COMT genotype in patients with WAD. The secondary aim was to investigate whether or not background factors, including mental health, were related to genotype and non-recovery. Methods: A total of 133 patients with neck pain after a whiplash trauma were included. Background factors were collected and blood samples were taken during the acute phase after the accident. DNA was isolated from blood and used to genotype the SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes were estimated and haplogenotypes inferred. The patients were followed up after 12 months and asked to rate their recovery including pain, mental health and quality of life. Results: The overall reported non-recovery rate at 12 months was 44% with no significant differences in distribution of the COMT haplotypes. High levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident were associated with non-recovery, but not related to the haplotypes. None of the other background factors were related to the haplotypes or non-recovery. Conclusion: No association between self-reported non-recovery or pain levels and COMT haplotypes in patients with acute whiplash injuries could be detected. Independent replications are necessary to discard the hypothesis that COMT haplotypes do not influence non-recovery or pain levels in patients with acute whiplash injuries. High levels of initial pain and anxiety were associated with non-recovery, thereby confirming previously published reports