No abstract

The Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) yields reliable DSM-IV diagnoses for a variety of psychiatric disorders, including alcohol and drug dependence. This study examines the reliability of individual DSM-IV criteria for lifetime substance dependence diagnoses and the impact of those criteria on diagnostic reliability.Methods-Two hundred ninety-three subjects (52.2% women; 38.2% African American, 46.8% European American, 7.5% Hispanic) were interviewed twice over a two-week period to examine the inter-rater reliability (n = 173) or test-retest reliability (n = 120) of the SSADDA. Cohen's κ statistic and its confidence interval were used to assess the reliability of individual diagnostic criteria.Results-Overall, the inter-rater reliability estimates were excellent for individual DSM-IV criteria for nicotine and opioid dependence; good for alcohol and cocaine dependence, and fair for dependence on cannabis, sedatives and stimulants. The impact of any individual criterion on diagnostic reliability was minimal, consistent with the notion that the DSM-IV diagnosis of substance dependence measures an underlying construct that is relatively consistent across specific groups of substances.Conclusions-These results, combined with results from a study of the SSADDA's diagnostic reliability (Pierucci-Lagha et al., 2005), show that the instrument can be used reliably to assess substance dependence.

GABA A receptors are involved in the subjective effects of alcohol. Endogenous neuroactive steroids interact with GABA A receptors to mediate several behavioral effects of alcohol in rodents. Based on a haplotypic association of alcohol dependence with the gene encoding the GABA A receptor a-2 subunit (GABRA2), we examined whether GABRA2 alleles are associated with the subjective response to alcohol. We also examined whether finasteride (a 5-a steroid reductase inhibitor), which blocks the synthesis of some neuroactive steroids, reduces the subjective response to alcohol. In all, 27 healthy social drinkers (15 males) completed a randomized, double-blind, placebo-controlled study of high-dose finasteride. After being pretreated with study drug, subjects consumed three alcoholic drinks. Subjective effects were measured repeatedly over the ascending blood alcohol curve. To examine the moderating role of genetic variation in GABRA2, a single-nucleotide polymorphism that was informative in association studies was included as a factor in the analysis. Subjects homozygous for the more common A-allele (n ¼ 7) showed more subjective effects of alcohol than did individuals with one or two copies of the alcohol dependence-associated G-allele (n ¼ 20, including two homozygotes). Among the A-allele homozygotes, there was a greater reduction in several subjective effects during the finasteride session compared to the placebo session. These findings provide preliminary evidence that the risk of alcoholism associated with GABRA2 alleles may be related to differences in the subjective response to alcohol. The effects of finasteride provide indirect evidence for a mediating role of neuroactive steroids in some of the subjective effects of alcohol.

An oral solution of ondansetron seems suitable for the treatment of alcohol dependence, yielding findings consistent with evidence from a placebo-controlled trial that ondansetron, at a dosage of 4 microg/kg twice daily, is of value in the treatment of EOAs.

Background: GABA A receptors are an important site of action of endogenous neurosteroids and an important mediator of several behavioral effects of alcohol. This study examined the effects of alcohol on plasma steroid hormone concentrations on the hypothesis that the endocrine effects mediate some of the subjective effects of alcohol. Methods: Thirty-two healthy subjects (17 men) with no history of a substance use disorder participated in this human laboratory study. All subjects consumed three standard drinks of grain alcohol. Subjective measures and blood samples for steroid concentrations were collected at baseline and 40 min after alcohol consumption. Results: Alcohol increased self-reported stimulation, alcohol liking, and desire for more alcohol. Alcohol also increased pregnenolone (PREG) and dehydroepiandrosterone (DHEA) concentrations, while it decreased progesterone (PROG) and allopregnanolone (ALLO) concentrations, as well as ALLO/PREG and PROG/PREG ratios. In men, the change in PREG concentration was significantly correlated with alcohol liking, while the alcohol-induced change in ALLO concentration correlated significantly with both alcohol liking and desire for more alcohol. Discussion: These findings provide preliminary support for the hypothesis that endogenous neurosteroids mediate some of the subjective effects of alcohol. Efforts to replicate these findings should aim to specify more clearly the nature and time course of the effects.

Interferon-alpha (IFN-α) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including the quality of life. Defining relevant risk factors for IFN-α induced depression is essential in order to identify prophylactic treatment strategies. We examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-α-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-α and ribavirin. Depressive symptoms were assessed at 0, 12, and 20 weeks of treatment. Depressive symptoms increased during antiviral treatment. 5-HTTLPR genotype moderated IFN-α-induced depressive symptoms in both Non-Hispanic Caucasians (NHCs; p = 0.009) and Hispanics (p = 0.036), though the opposite risk allele was associated with depression in the two populations. 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-α-therapy for CHC in a population-specific manner.

Background-Aripiprazole is an atypical antipsychotic with partial agonist activity at D 2 receptors, which could reduce the reinforcing effects of alcohol. The present study examined whether aripiprazole modifies the behavioral and physiological effects of a moderate dose of alcohol in a group of social drinkers.

This study provides support for the role of serotonergic neurotransmission in modulating mood and alcohol urges, and underscores the utility of these effects as a phenotype for genetic analysis. These findings may also help to identify alcoholics who are at greatest risk for MDD.