***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Excessive alcohol use , a major cause of morbidity and mortality , is less well understood than other addictive disorders . Dopamine release in ventral striatum is a common element of drug reward , but alcohol has an unusually complex pharmacology , and humans vary greatly in their alcohol responses . This variation is related to genetic susceptibility for alcoholism , which contributes more than half of alcoholism risk . Here , we report that a functional OPRM1 A118 G polymorphism is a major determinant of striatal dopamine responses to alcohol . Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions , and examined for striatal dopamine release using positron emission tomography and [11C]-raclopride displacement . A striatal dopamine response to alcohol was restricted to carriers of the minor 118 G allele . To directly establish the causal role of OPRM1 A118 G variation , we generated two humanized mouse lines , carrying the respective human sequence variant . Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1 - 118GG than in h/mOPRM1 - 118AA mice . OPRM1 A118 G variation is a genetic determinant of dopamine responses to alcohol , a mechanism by which it likely modulates alcohol reward Alcohol-dependent patients ( N = 97 ) were r and omly assigned to receive either naltrexone or placebo and either relapse prevention therapy or supportive therapy . The present report explored the hypothesis that patients could be matched to the above treatments on the basis of specific pretreatment characteristics . Treatment matching variables explored included craving , alcohol dependence severity , and cognitive measures of learning and memory . Results of linear regression analyses tentatively suggest that patients experiencing higher levels of craving and poorer cognitive functioning may derive the greatest benefit from naltrexone versus placebo . For psychotherapy , lower levels of verbal learning were associated with poorer drinking outcomes for relapse prevention therapy but not for supportive therapy . Conversely , higher levels of verbal learning were associated with better outcomes for relapse prevention therapy but not for supportive therapy AIMS To investigate the relationship between the sweet liking/sweet disliking phenotype ( a putative probe of brain opioid function ) , craving for alcohol and response to treatment with naltrexone  in individuals with alcohol dependence . METHODS Forty individuals with alcohol dependence were enrolled in a 12-week open-label study of 50 mg of naltrexone with four sessions of motivational enhancement therapy . Prior to treatment , individuals completed a sweet preference test and the Penn Alcohol Craving Scale . Subjects were categorized as sweet liking ( SL ) , n = 15 , or sweet disliking ( SDL ) , n = 25 , via a st and ard sweet tasting paradigm . The sweet tasting results were blinded to the subjects and to treatment staff . SL status , pretreatment craving and their interaction were examined as predictors of frequency of abstinent days and heavy drinking days during treatment with naltrexone . RESULTS SL and SDL subjects achieved similar reductions in percent heavy drinking days with treatment . During treatment , SDL subjects had 48 % abstinent days compared to 30 % for SL subjects ( P = 0.034 ) . Pretreatment craving did not predict % heavy drinking days or % abstinent days . An interaction effect was found between the SL/SDL phenotype and pretreatment craving such that SL subjects with high craving demonstrated higher rates of percent abstinent days whereas SDL subjects with high craving demonstrated lower rates of percent abstinent days , P < 0.001 . CONCLUSIONS These findings indicate that the SL/SDL phenotype may predict variation in response to naltrexone and /or counseling treatment . Furthermore , the SL/SDL phenotype may interact with craving to provide a more robust prediction of outcome with naltrexone or counseling AIMS To determine the clinical ly ascertained variables that are related to satisfactory response to naltrexone ( NTX ) treatment of alcohol dependence after detoxification . METHODS The use of intake and outcome variables were measured in a r and omized 3-month open-controlled trial comparing the effects of naltrexone plus psychotherapy treatment versus psychotherapy treatment alone on the maintenance of abstinence in the final 28 days ( n = 336 , all male ) . RESULTS Predictors of a positive response to NTX treatment were family history of alcoholism ( P = 0.010 ) , early age at onset of drinking problems  ( P = 0.014 ) and comorbid use of other drugs of abuse ( P < 0.001 ) . Among the subjects not treated with NTX , the greater the number of predictor variables , the lower the final 28 days abstinence rates ( P = 0.00003 ) , but this was not the case in patients treated with NTX ( P = 0.844 ) . CONCLUSIONS Patients with these features , suggesting biological vulnerability overall have poorer outcomes , but this can be reduced with NTX treatment . The type of alcoholism should be considered before deciding on the pharmacological strategy CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 Variation at a single nucleotide polymorphism in the μ-opioid receptor gene ( OPRM1 ) , A118 G ( Asn40Asp ) , may moderate naltrexone ( NTX ) effects in alcohol dependence . Both NTX and A118 G variation have also been reported to affect alcohol cue-elicited brain activation . This study investigated whether sub-acute NTX treatment and A118 G genotype interacted in their effects on cue-elicited activation of the ventral striatum ( VS ) , medial prefrontal cortex ( mPFC ) , and orbitofrontal cortex ( OFC ) . Secondarily , variation at a variable number t and em repeat polymorphism in the dopamine transporter gene ( DAT1/SLC6A3 ) , which has been associated with increased reward-related activation in VS , was analyzed as a moderator of medication and A118 G effects . Seventy-four non-treatment-seeking alcohol-dependent individuals , half preselected to carry at least one copy of the A118 G G ( Asp ) allele , were r and omized to NTX ( 50 mg ) or placebo for 7 days , and performed an fMRI alcohol cue reactivity task on day 6 . Region-of-interest analyses indicated no main effects of medication or A118 G genotype . However , these factors interacted in their effects on OFC activation , such that , among NTX-treated individuals , G-allele carriers had less activation than A-allele homozygotes . DAT1 variation also moderated medication/A118 G effects . There was a three-way interaction between medication and A118 G and DAT1 genotypes on VS activation , such that , among G-allele carriers who received NTX , DAT1 10-repeat-allele ( 10R ) homozygotes had less activation than 9-repeat-allele ( 9R ) carriers . Further , 10R homozygotes who received NTX had less mPFC activation than 9R carriers . Polymorphic variation in OPRM1 and DAT1 should be considered in future studies of NTX , particularly regarding its effects on reward processing In alcoholism , both relapse to alcohol drinking and treatment response are suggested to be genetically modulated . This study set out to determine whether the top 15 single nucleotide polymorphisms ( SNPs ) of a recent genome-wide association ( GWA ) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a r and omized , double-blind , placebo-controlled trial with acamprosate , naltrexone or placebo .  The single nucleotide polymorphism , rs13273672 , an intronic SNP in the gene for GATA-binding protein 4 ( GATA4 ) , was associated with relapse within the 90-day medical treatment period ( P<0.01 ) . Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate ( P<0.01 ) . In line with the observation that natriuretic peptide promoters are modulated by GATA4 , a significant gene dose effect on the variance of atrial natriuretic peptide ( ANP ) plasma concentration in the different GATA4 genotypes ( P<0.01 ) was found . Hence , genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels . These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate Given the evidence from retrospective studies indicating that alcohol-dependent patients with homozygous or heterozygous A118 G variant of the & mgr;-opioid receptor , OPRM1 , gene have significantly better outcomes when treated with naltrexone ; this study examined this prospect ively in 100 alcohol-dependent participants prescribed naltrexone for 12 weeks and offered six sessions of cognitive-behavioral therapy or intervention . Comparisons were made among OPRM1 genotypic groups on several outcome measures . Naltrexone treatment produced significant decreases in self-reported and objective indicators of alcohol use and craving from baseline ( P<0.0001 and 0.017 , respectively ) , particularly during the first 2 months of treatment , with 68 % completing the study . However , there was no evidence of a significant association between OPRM1 A118 G genotype and treatment success on any of the outcome measures . Therefore , while naltrexone was an effective treatment for alcohol dependence , the OPRM1 A118 G genotype was not a predictor of success OBJECTIVE Primary outcomes from the COMBINE Study indicated support for naltrexone ( Revia ) on measures of abstinence and time to heavy drinking ; however , effect sizes were modest . The delineation of individual difference variables that qualify these results could aid efforts to target treatment approaches appropriately . Laboratory and clinical studies have found greater effectiveness of naltrexone among men and those with familial alcoholism . The present study used multilevel modeling to investigate family history of alcoholism ( FHA ) based on first-degree relatives and gender as moderators of naltrexone 's effects on three drinking outcomes : percentage of days abstinent , drinks per drinking day , and percentage of heavy drinking days .  METHOD Data were drawn from the COMBINE public data set and included 
    Output:
    
Studies to date point to two potential moderators-family history and presence of the OPRM1 Asn40Asp polymorphism-as having the strongest evidence .