CLOCK is suggested to associate with comorbid alcohol use and depressive disorders

<p>Abstract</p> <p>Background</p> <p>Depression and alcohol abuse or dependence (AUD) co-occur in the general population more frequently than expected by chance. Alcohol use influences the circadian rhythms generated by the central pacemaker in the suprachiasmatic nucleus, and circadian rhythm alterations in turn are common in depressive disorders as well as among persons addicted to alcohol.</p> <p>Methods</p> <p>32 SNPs in 19 circadian clockwork related genes were analyzed using DNA from 76 individuals with comorbid depression and AUD, 446 individuals with AUD and 517 healthy controls with no psychiatric diagnosis. The individuals participated in a nationwide health examination study, representative of the general population aged 30 and over in Finland.</p> <p>Results</p> <p>The <it>CLOCK </it>haplotype TTGC formed by SNPs rs3805151, rs2412648, rs11240 and rs2412646, was associated with increased risk for comorbidity (OR = 1.65, 95% CI = 1.14-2.28, P = 0.0077). The SNPs of importance for this suggestive association were rs2412646 and rs11240 indicating location of the functional variation in the block downstream rs2412648. There was no indication for association between <it>CLOCK </it>and AUD.</p> <p>Conclusion</p> <p>Our findings suggest an association between the <it>CLOCK </it>gene and the comorbid condition of alcohol use and depressive disorders. Together with previous reports it indicates that the <it>CLOCK </it>variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD.</p

CRY2 Genetic Variants Associate with Dysthymia

Peer reviewe

NPAS2 and PER2 are linked to risk factors of the metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Mammalian circadian clocks control multiple physiological events. The principal circadian clock generates seasonal variations in behavior as well. Seasonality elevates the risk for metabolic syndrome, and evidence suggests that disruption of the clockwork can lead to alterations in metabolism. Our aim was to analyze whether circadian clock polymorphisms contribute to seasonal variations in behavior and to the metabolic syndrome.</p> <p>Methods</p> <p>We genotyped 39 single-nucleotide polymorphisms (SNP) from 19 genes which were either canonical circadian clock genes or genes related to the circadian clockwork from 517 individuals drawn from a nationwide population-based sample. Associations between these SNPs and seasonality, metabolic syndrome and its risk factors were analyzed using regression analysis. The p-values were corrected for multiple testing.</p> <p>Results</p> <p>Our findings link circadian gene variants to the risk factors of the metabolic syndrome, since <it>Npas2 </it>was associated with hypertension (P-value corrected for multiple testing = 0.0024) and <it>Per2 </it>was associated with high fasting blood glucose (P-value corrected for multiple testing = 0.049).</p> <p>Conclusion</p> <p>Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist.</p

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Peer reviewe

Localization of cytochrome P450 CYP2S1 expression in human tissues by in situ hybridization and immunohistochemistry

CYP2S1 is a recently discovered dioxin-inducible member of the cytochrome P450 superfamily. It has been shown to be involved in the metabolism of some aromatic hydrocarbons as well as retinoic acid, suggesting a role in biotransformation of both exogenous and endogenous compounds. In this study, we used mRNA in situ hybridization and immunohistochemistry to investigate the cellular localization of CYP2S1 in various human tissues using tissue microarrays. High expression levels were observed mainly in epithelial cell types, especially in the epithelia frequently exposed to xenobiotics. In the respiratory tract, the expression was strong in nasal cavity, bronchi, and bronchioli, whereas it was low in the alveolar lining cells. Similarly, CYP2S1 was highly expressed in the epithelial cells throughout the gastrointestinal tract. Strong epithelial expression was also observed in uterine cervix, urinary bladder, and skin. In many exocrine glands (e.g., adrenal gland and pancreas), secretory epithelial cells showed moderate to strong expression levels. In the liver, the expression was low. CYP2S1 was highly expressed in epithelial cells that are major targets for carcinogen exposure and common progenitor cells to tumor development. Indeed, we found strong CYP2S1 expression in many tumors of epithelial origin.</p

A Randomised, Double-Blind, Placebo-Controlled Trial of As-Needed Naltrexone in the Treatment of Pathological Gambling

&lt;b&gt;&lt;i&gt;Background/Aims:&lt;/i&gt;&lt;/b&gt; Effective treatment strategies are needed for the treatment of pathological gambling (PG). The efficacy of as-needed naltrexone was assessed in a single-centre, randomised, double-blind, placebo-controlled trial. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; The participants (n = 101) received either as-needed placebo or naltrexone (50 mg) and psychosocial support for 20 weeks. The primary outcome measure was the severity of PG assessed by the Yale-Brown Obsessive Compulsive Scale adapted for PG (PG-YBOCS). Secondary gambling-related outcome measures included thoughts/urges and behaviour subscales of PG-YBOCS as well as the highest daily expenditure and gambling frequency. In addition, RAND-36 scales of emotional well-being and social functioning were used as outcomes. The results were analysed using the intention-to-treat principle and linear random effects modelling. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; No significant treatment group differences were found. In an exploratory analysis, emotional well-being increased in a subgroup of participants with &lt;i&gt;AA&lt;/i&gt; genotype of opioid receptor, mu 1 &lt;i&gt;(OPRM1) A118G&lt;/i&gt; polymorphism (p = 0.02). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Overall, the as-needed naltrexone may not provide substantial additional benefit for PG patients receiving psychosocial support. Replication by larger scale studies is warranted to further evaluate naltrexone administration schedules for the treatment of PG and the role of &lt;i&gt;OPRM1&lt;/i&gt;.</jats:p