Henry R Kranzler

..Pharmacotherapy studies in alcohol dependence (AD) are generally of short duration and do not include post-treatment follow-up. We examined the durability of treatment effects in a placebo-controlled trial of sertraline for AD...

..We compared 3 different methods to subtype alcoholics...

..Because AD is common, particularly in medical settings, and selective serotonin reuptake inhibitors are widely prescribed by practitioners, these findings have potential public health significance and warrant further evaluation...

..The complex structure of CRHR1 may help to explain why some variants in the gene moderate the effects of an ACE only on depression risk while others moderate the effect of an ACE only on AD risk...

..019). We conclude that two independent CNR1 variants have significant interaction effects on risk for CD in EAs; they may also have effects on risk for CD in AAs...

..The functional promoter GAD2 -243 A > G variant may influence risk for AD in some populations, or its role may be limited to susceptibility to severe AD...

..Functional studies of these loci are warranted. These results provide additional information useful in evaluating the many earlier discrepant findings regarding association of DRD2 with substance dependence...

..SNP2 or SNP6 was the marker genetically closest to the functional risk loci for both alcohol dependence and drug dependence...

..Previous studies generally focused on its effect on depressive symptoms; little is known about its moderation of the development of posttraumatic stress disorder (PTSD)...

..These findings, obtained using a series of powerful and reliable analytic methods, may also help to explain the high rate of co-morbidity between AD and DD...

..Because comorbid AD with DD (AD+DD) is common, we hypothesized that heterogeneity of the SD diagnoses studied might have contributed to the inconsistency of prior results...

..The complexity of these relationships, many of which replicate between our independent samples, may explain prior inconsistent results...

..The negative results for AFDs, PTSD, and schizophrenia could be due to the low statistical power. Further study with larger samples is warranted...

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..These findings may aid in understanding the genetic association of this locus with alcohol dependence in several populations...

..Following initial reports of association of CNR1 with SD, we studied multiple markers at this locus in a large case-control sample...

..Design  Secondary data analysis using pooled data from family-based and case-control genetic studies of SD...

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..Childhood abuse is an important predictor of ASPD. We examined 5-HTTLPR genotype and adverse childhood events (ACEs) as risk factors for ASPD in a SD sample...

..We cannot exclude the possibility that the results might have been influenced by selection bias due to the multisite nature of the study...

..These findings suggest that OPRM1 intronic variants play a role in susceptibility to AD and DD in populations of European ancestry...

..The pro-opiomelanocortin gene (POMC) encodes several peptides important for endogenous opioidergic neurotransmission. We tested whether POMC genetic variation affects risk for substance dependence...

..008 <or= P <or= 0.060). The present study demonstrates that the ADH1A variation may contribute to the genetic component of variation in personality traits and SD...

..The effects of finasteride provide indirect evidence for a mediating role of neuroactive steroids in some of the subjective effects of alcohol...

..The goal of this study was to investigate the relationship between the NOTCH4 gene and schizophrenia in African American (AA) and European American (EA) subjects...

..CONCLUSIONS: Severity of cocaine dependence and age of onset appear to be important risk factors for CIP. Concordance for CIP between siblings did not emerge as significant in our analyses...

..Because the convergence of these disorders may provide a refined phenotype, we examined the association of serotonin (5-HT) transporter linked polymorphic region (5-HTTLPR) alleles to comorbid alcohol dependence and major depression...

..This study provides further evidence of a gene x environment effect of FKBP5 and childhood abuse on the risk for PTSD in AAs. Further study is required in other populations...

..The basis for this finding is unknown, but it may have implications for sub-typing alcoholics...

..These results are an initial step in identifying genes for opioid dependence on the basis of a genomewide investigation (i.e., a study not conditioned on prior physiological candidate-gene hypotheses)...

..002). CHRM2 variation may contribute to the genetic component of variation in personality traits. Personality traits might substantially underlie the heritable component of SD...

..Strong associations between ADH4 variation and SD have been reported. We aimed to investigate the relationship between ADH4 variation and personality traits in the present study...

..To identify and validate homogeneous subtypes of opioid use and related behaviors...

..We examined reward drinking (drinking-to-enhance motives) as a comparison and to see whether these effects varied across gender...

..We examined this polymorphism as it interacted with negative life events to predict drinking and drug use in college students...

..Based on our robust family-controlled and unrelated-affected analyses, we conclude that COMT is associated with CIP, possibly as a result of its role in the metabolism of dopamine and norepinephrine...

..Risk loci in several populations have been identified with genetic linkage analysis. To date, there has been no published linkage study of AD focused on African Americans (AAs)...

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..Using rigorous study designs that account for possible population stratification, these findings confirm and extend our original observations indicating that variation at ADH4 predisposes to alcohol and drug dependence...

..This study aimed to test the association in two common US populations by using powerful analytic methods...

..Nicotine dependence (ND) is costly to societies worldwide, moderately heritable, and genetically complex. Risk loci can be identified with genetic linkage analysis independent of prior physiological hypotheses...

..The present study demonstrated that the ADH7 variation may contribute to the genetic component of variation in personality traits, with the risk for SD and personality traits being partially shared...

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..Comorbid substance use and psychiatric disorders are very common among individuals with cocaine dependence. Comorbid ADHD increases the odds of an individual endorsing CIP, suggesting some common basis for these phenomena...

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..We also found that several ADH genes and the ALDH2 gene were susceptibility loci for AD, and the associations were best explained by several independent risk genes...

..6%) (P=0.049). Sex and CA did not significantly influence OPRM1 promoter methylation levels. Our findings suggest that OPRM1 promoter hypermethylation may increase the risk for AD and other substance dependence disorders...

..80, 95% CI=1.18-2.73, P=0.0044; FTND: OR=1.79, 95% CI=1.11-2.88, P=0.012). No interaction was found in women. This study provides evidence of a sex-specific gene × environment effect of CHRNA5 and childhood adversity on the risk for ND...

..This is the first linkage evidence supporting existence of genetic loci influencing risk for several comorbid disorders simultaneously in two major US populations...

..TNN is involved in neurite outgrowth and cell migration in hippocampal explants, and TNR is an extracellular matrix protein expressed primarily in the central nervous system...

..07, P = 4.2E-05). No SNPs or haplotypes were associated with PAFDs in men or with CAFDs in either sex. We conclude that variation in NGFB is a risk factor for PAFDs in women, but not for CAFD...

..2005). A 24-week, randomized, double-blind, placebo-controlled study established the efficacy and safety of XR-NTX in this patient population. In this report, the effect of XR-NTX on quality of life (QOL) was examined...

..Adverse childhood events (ACEs) are associated with negative health outcomes. We examined ACEs as risk factors for substance dependence (SD) and the mediating effects of mood and anxiety disorders on the relations between ACEs and SD risk...

..We conclude that variation in KIBRA influences cognitive flexibility in a population-specific way, and that current smoking status moderates this effect...

..The present study examines the association of a GABRA2 SNP with another definition of alcohol involvement and with the effects of psychosocial treatment...

..In conclusion, XR-NTX 380 mg prolonged abstinence and reduced the number of heavy drinking days and drinking days in patients who were abstinent for as few as 4 days before treatment initiation...

..We examined the prevalence and course of psychiatric and substance dependence (SD) disorders in subjects with SD and attention deficit hyperactivity disorder (ADHD)...

..34 (95% CI = 1.11-1.63)]. Allelic variation at 5-HTTLPR contributes to risk for AD, with the greatest effect observed among individuals with a co-occurring clinical feature...

..These findings fail to replicate the original report of an association between SNPs adjacent to an alternative CNR1 exon 3 transcription start site and polysubstance abuse...

..The goal of this study was to test whether GABRA2 is associated with alcohol dependence in a sample of Russian alcohol-dependent men...

..The present study examined whether aripiprazole modifies the behavioral and physiological effects of a moderate dose of alcohol in a group of social drinkers...

..Furthermore, these results suggest that common genetic variation within the GAD67 gene does not play a major role in the predisposition to unipolar depression...

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..Interferon-alpha (IFN-alpha) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life...

..Although developed for use in genetic studies, its broad and detailed coverage of disorders and computer-assisted format will allow it to be used in a variety of applications requiring careful diagnostic assessment...

..CRBs also correlate with hallucinations and delusions induced by cocaine, but to a lesser degree. Our findings suggest that there may be some common vulnerability factors that contribute to both cocaine-induced psychosis and CRBs...

..003). These findings replicate and extend recently reported findings, which together underscore the potential contribution of polymorphic variation at the GABRA2 locus to the risk for alcohol dependence...

..These findings suggest that OPRM1 may play a role in the pathophysiology of substance dependence and this role is population- and diagnosis-specific...

..Results suggest that co-occurring substance dependence and psychiatric disorders warrant attention in cocaine dependence assessment, treatment, and self-help...

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..This work suggests that variations in the TPH2 gene are not a risk factor for the development of cocaine dependence, but these findings require confirmation in larger, independent samples of cocaine-dependent and control subjects...

..However, efforts are needed to improve long-term abstinence rates and smoking outcomes among women with a history of depression...

..e., "telescoping") of alcohol-related complications. This phenomenon also appears to be evident in drug-dependent women, though the data available to support telescoping in drug dependence is less abundant...

..38%; P = 0.003) and a non-significant excess of the T allele in schizophrenia (44%; P = 0.29). The allele frequency for subjects with alcohol dependence did not differ from controls...

..35 for membership in the "Moderate Cocaine and Opioid Abuse" cluster on chromosome 18. These results provide a basis for the identification of specific genes contributing to risk for these traits...

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..To determine the impact of treatment with oral naltrexone on healthcare costs in patients with alcohol-related disorders...

..If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone...

..We tested whether the Pro7 allele is associated with alcohol dependence in European Americans (EA)...

..In contrast, heavy drinking women showed no benefit from daily naltrexone treatment. Further evaluation of the efficacy of targeted treatments and of daily naltrexone and the relationship of these treatments with gender is warranted...

..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...

..We examined prescriptions for oral naltrexone in a large, nationally distributed treatment population to identify characteristics and health-care utilization patterns associated with persistence...

..Efforts to improve naltrexone compliance have included the development of injectable, long-acting depot formulations...

..The polymorphism occurs commonly in European Americans and some other population groups, underscoring its potential phenotypic significance...

..We examined opioid receptor gene polymorphisms as moderators of the therapeutic effects of the opioid antagonist nalmefene...

..CONCLUSIONS: The SIP is useful for measuring drinking consequences in a sample of problem drinkers, and the subscale scores can be interpreted clinically. Further research on the SIP in other populations is warranted...

..Conclusion: Despite no evidence in this study for allelic association of HTR1B to antisocial substance dependence, further evaluation of the hypothesized association is warranted in other population groups...

..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)...

..These findings underscore the utility of daily measurement for understanding the processes that underlie pharmacological interventions for problem drinking...

..However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited...

..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...

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..These findings suggest that patients who report current smoking should routinely be asked about their current alcohol consumption. Interventions should then be tailored to address smoking and, if appropriate, hazardous drinking as well...

..These findings do not support the hypothesis that sucrose preference is positively associated with either a personal lifetime history of AD or a family history of alcoholism...

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..This study examines the reliability of individual DSM-IV criteria for lifetime substance dependence diagnoses and the impact of those criteria on diagnostic reliability...

..Efforts to replicate these findings are warranted, since they suggest that schedules of medication administration other than daily should be evaluated for treatment of problem drinking...

..Further research should aim to ascertain the factors affecting the relationship between compliance and outcomes...

..Despite these advantages, no published studies have used IVR in alcohol pharmacotherapy trials...

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