Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability. Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3 0 -UTR of the CHRNA3 gene and nicotine dependence. In this study we performed a comprehensive association analysis of the CHRNA5-CHRNA3-CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence. Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence. These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation. Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA. Molecular Psychiatry (2009) 14, 501-510; doi:10.1038/mp.2008 published online 15 April 2008 Keywords: nicotinic acetylcholine receptors; mRNA expression; alcohol dependence; polymorphism IntroductionIt is well established that alcohol and tobacco use are highly correlated in humans. Current smokers are more likely to drink heavily and to binge drink than those who have never smoked, and alcoholics smoke more heavily and endorse nicotine withdrawal symptoms at a higher rate than nonalcoholics. [1][2][3][4][5] The National Longitudinal Epidemiologic Survey reported that early onset smoking was a significant predictor of lifetime drinking and subsequent progression to lifetime alcohol abuse and dependence. 6 Both alcohol dependence and habitual smoking are transmitted in families and genetic factors contribute to the development of both of these disorders. [7][8][9][10][11][12][13][14] Evidence from electrophysiological, pharmacological and neurochemical studies suggest that ethanol may interact with nicotinic acetylcholine receptors (nAChR). [15][16][17][18] The nAChR gene family has 11 known subunits (a 2 , a 3 , a 4 , a 5 , a 6 , a 7 , a 8 , a 9 and b 2 , b 3 , b 4 ); these subunits form pentameric receptors with different combinations of subunits. 19,20 The effects of ethanol on nAChRs depend on the receptor subunit composition. Studies using different nAChR subtype compositions expressed in Xenopus oocytes demonstrate that ethanol tends to increase nicotine responsiveness in a2b2, a3b2 and a4b2 receptor subtypes, whereas low concentrations of et...

Analyses examined whether addicts reporting themselves coerced into drug abuse treatment by actions of the criminal justice system differed from voluntary admissions in their response to treatment, and whether such responsiveness varied across gender or ethnicity. Six hundred eighteen methadone maintenance clients admitted to programs in six southern California counties were categorized into high, moderate, and low legal coercion levels. Multivariate analysis of variance procedures for repeated measures (before, during, and after initial treatment episode) were used to test relevant hypotheses. Dependent variables included criminal justice system contact, criminal activities, drug and alcohol involvement, and measures of social functioning. Few differences within any measured domain were found among the three groups. All groups were similar in showing substantial improvement in levels of narcotics use, criminal activities, and most other behaviors during treatment with some regression in these behaviors posttreatment. Results support legal coercion as a valid motivation for treatment entry; those coerced into treatment respond in ways similar to voluntary admissions regardless of gender or ethnicity.

Although previously not described, the diagnosis of calcified dural meningioma en plaque should be considered in all patients presenting with spinal cord and/or nerve root compression,even at cervical levels. Although ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum are more common etiologies of partially circumferential spinal calcification, dural-based meningiomas with extension into the surrounding ligaments demand early recognition because they can be associated with a poorer prognosis.

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