Targeted versus daily naltrexone: secondary analysis of effects on average daily drinking.

Background: To extend our previous findings that naltrexone reduced the likelihood of heavy drinking on a given day among problem drinkers, while targeted administration reduced the likelihood of any drinking, we examined the effects of naltrexone and targeted administration on the continuous outcome of drinks/day. Because treatment response may differ by gender, we also compared the effects on this factor.

Methods: In a double-blind, placebo-controlled study, problem drinkers (n=150, 58% men) were randomly assigned to 8 weeks of treatment with naltrexone (50 mg/day) or placebo, either daily or on a targeted schedule.

Variation at APOE and STH loci and Alzheimer's disease.

Background: The apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD). Many studies have shown an association between the APOE gene and AD. Association between AD and the newly discovered saitohin (STH) gene, nested within the intron of the tau gene, has been reported.

Association between two mu-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence.

We examined 13 single nucleotide polymorphisms (SNPs) spanning the coding region of the mu-opioid receptor gene (OPRM1), among 382 European Americans (EAs) affected with substance dependence [alcohol dependence (AD) and/or drug dependence (DD)] and 338 EA healthy controls. These SNPs delineated two haplotype blocks. Genotype distributions for all SNPs were in Hardy-Weinberg equilibrium (HWE) in controls, but in cases, four SNPs in Block I and three SNPs in Block II showed deviation from HWE.

Advances in the pharmacotherapy of alcoholism: challenging misconceptions.

This article highlights the proceedings of a symposium presented at the 28th Annual Scientific Meeting of the Research Society on Alcoholism in Santa Barbara, CA, June 27, 2005. The organizer and chair was Henry R. Kranzler.

Sertraline treatment of co-occurring alcohol dependence and major depression.

Background: Major depressive disorder occurs commonly in association with alcohol dependence, both in clinical samples and in the community. Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results. This multicenter, double-blind, placebo-controlled trial of sertraline was designed to address many of the potential methodological shortcomings of studies of co-occurring disorders.

Risk factors for cocaine-induced paranoia in cocaine-dependent sibling pairs.

Objective: Cocaine-induced paranoia (CIP), an irrational intense suspicion of others, is a common manifestation of cocaine dependence. Both environmental and genetic factors are thought to play a role, but the specific nature of such contributions is poorly understood.

Methods: Demographic, diagnostic, and cocaine-use data were obtained from 420 cocaine-dependent, genetically confirmed, full-sibling pairs (N=840 subjects) interviewed with the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

Association of an Asn40Asp (A118G) polymorphism in the mu-opioid receptor gene with substance dependence: a meta-analysis.

Introduction: The mu-opioid receptor has been implicated in the pathogenesis of dependence on opioids, alcohol, nicotine, and cocaine. Studies examining the association of the mu-opioid receptor gene (genetic locus OPRM1) with substance dependence (SD) have focused on the Asn40Asp (A118G) single nucleotide polymorphism (SNP).

Method: We used meta-analysis to examine the literature on the association of Asn40Asp with SD.

Incentive program decreases no-shows in nontreatment substance abuse research.

This study examined the use of a low-cost incentive program to decrease the rate of unanticipated no-shows in a nontreatment study of the genetics of substance dependence. Low-cost retail items (such as calling cards or gift certificates) were offered contingent on attendance at the first scheduled research appointment. Although the intervention did not result in an increase in the rate of attendance at appointments, it reduced the likelihood of unanticipated no-shows by almost 50%.

Subjective effects and changes in steroid hormone concentrations in humans following acute consumption of alcohol.

Background: GABAA 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.

Treatment-refractory schizophrenia in children and adolescents: an update on clozapine and other pharmacologic interventions.

Treatment-refractory early-onset schizophrenia is a rare but severe form of the disorder associated with poor premorbid function and long-term disability. The currently available evidence suggests that clozapine remains the most efficacious treatment for the amelioration of both positive and negative symptoms of the disorder and problematic aggressive behaviors. Clozapine use in children and adolescents, however, is limited by its association with hematologic adverse events and an increased frequency of seizure activity.

ADH4 gene variation is associated with alcohol dependence and drug dependence in European Americans: results from HWD tests and case-control association studies.

The alcohol dehydrogenase (ADH) family constitutes one of the key sets of enzymes responsible for the oxidation of alcohol. The ADH4 gene, an important member of this family, is a functional and positional candidate for alcohol dependence. The present study aimed to investigate the relationship between ADH4 gene variation and alcohol dependence and drug dependence in European-Americans (EAs) and African-Americans (AAs).

Characterization of a likelihood based method and effects of markers informativeness in evaluation of admixture and population group assignment.

Background: Detection and evaluation of population stratification are crucial issues in the conduct of genetic association studies. Statistical approaches useful for understanding these issues have been proposed; these methods rely on information gained from genotyping sets of markers that reflect population ancestry. Before using these methods, a set of markers informative for differentiating population genetic substructure (PGS) is necessary.

ADH4 gene variation is associated with alcohol and drug dependence: results from family controlled and population-structured association studies.

We found strong associations between ADH4 gene variation and alcohol and drug dependence by the Hardy-Weinberg Disequilibrium (HWD) test and case-control association analysis in an initial study. The present study aimed to confirm these findings by controlling for population stratification and admixture effects to which the HWD test and case-control association methods may be vulnerable. In addition to 365 unrelated healthy controls and 560 unrelated cases in the initial study, we evaluated 104 small nuclear families with affected offspring who had diagnoses of alcohol and/or drug dependence.

Hematological adverse events in clozapine-treated children and adolescents.

Objective: To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine.

Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and agranulocytosis (HAEs) development was determined for 172 eligible patients (mean age at clozapine initiation, 15.

The contribution of genetics to addiction therapy approaches.

Addictions, including alcohol dependence, which is the focus of this article, are complex genetic diseases. Recently, several individual genes that contribute to the risk for alcohol dependence have been identified, and more are expected to be in the near future. Among these are genes encoding alcohol and aldehyde dehydrogenases and GABA(A) receptor subunits.

CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case-control structured association study.

Cholinergic muscarinic 2 receptor (CHRM2) is implicated in memory and cognition, functions impaired in many neuropsychiatric disorders. Wang et al. [Wang, J.

Does effect size in naltrexone trials for alcohol dependence differ for single-site vs. multi-center studies?

Background: The opioid antagonist naltrexone was first shown in single-site trials to be efficacious in the treatment of alcohol dependence. Recent clinical trials of the medication have used multi-center designs, which permit greater generalization and increased statistical power. We compared effect sizes for these two kinds of trial design on the hypothesis that multi-center trials introduce sources of variation that reduce the observed effect size.

Genomewide linkage scan for cocaine dependence and related traits: significant linkages for a cocaine-related trait and cocaine-induced paranoia.

Risk for cocaine dependence (CD) is genetically influenced. We recruited a sample of small nuclear families (528 full and 155 half sibpairs) with at least one subject affected with CD. The sample was classified via Bayesian clustering as 45.

Diagnostic reliability of the Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA).

Unlabelled: The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) is a diagnostic instrument developed for studies of the genetics of substance use and associated disorders. The SSADDA provides more detailed coverage of specific drug use disorders, particularly cocaine and opioid dependence, than existing psychiatric diagnostic instruments. A computerized version of the SSADDA was developed to permit direct entry of subject responses by the interviewer.

Rating the severity and character of transient cocaine-induced delusions and hallucinations with a new instrument, the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP).

Background: Cocaine can induce transient psychotic symptoms. We examined the phenomenology of such cocaine-induced psychosis (CIP) using a modified version of the Scale for Assessment of Positive Symptoms (SAPS), a well-validated instrument for the assessment of schizophrenic psychosis.

Methods: We developed a new instrument, the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP), based on the well-validated SAPS.

Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population.

Background: Two recent large genetic studies in the US population have reported association between genetic variation in gamma-amino butyric acid alpha2 receptor subtype (GABRA2) and risk for alcohol dependence. The goal of this study was to test whether GABRA2 is associated with alcohol dependence in a sample of Russian alcohol-dependent men.

Methods: A total of 113 Russian alcohol-dependent men and 100 male population control subjects were recruited in St.

Drinking to cope: a comparison of questionnaire and electronic diary reports.

Objective: The purpose of this article is to assess the correspondence between questionnaire reports of dispositional drinking to cope (DTC) and different indices of daily DTC in a sample of nondependent heavy drinkers.

Method: Data from electronic diary (ED) records of interpersonal problems, negative affect, coping and drinking were used to examine how questionnaire reports of dispositional DTC corresponded to ED reports of daily DTC and to within-person associations among ED reports of negative affect, interpersonal problems and drinking. In the current study, 98 community-residing heavy drinkers using EDs recorded moods, interpersonal problems, coping attempts, desire to drink and drinking for 21 consecutive days.

Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial.

Context: Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited.