***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 Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy , we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins , namely ARRB2 and HINT1 . Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label r and omized trial . In a logistic regression model controlling for OPRM1 genotype , treatment type , and other covariates , we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up . Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up , but this may not be a pharmacogenetic effect , given that the participants were drug free during this time . Haplotype analysis did not reveal any significant associations for either gene . We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance ; however , interpretation of this finding is limited by the small number of participants with the minor alleles for both genes . Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation , further exploration of opioid pathway genes in larger prospect i ve pharmacogenetic trials may be warranted Prepulse inhibition ( PPI ) of the acoustic startle response ( ASR ) has been established as an operational measure of sensorimotor gating . Animal and human studies have shown that PPI can be modulated by dopaminergic , serotonergic , and glutamatergic drugs and consequently it was proposed that impaired sensorimotor gating in schizophrenia parallels a central abnormality within the corresponding neurotransmitter systems . Recent animal studies suggest that the opioid system may also play a role in the modulation of sensorimotor gating . Thus , the present study investigated the influence of the mu-opioid receptor agonist morphine on PPI in healthy human volunteers . Eighteen male , non-smoking healthy volunteers each received placebo or 10 mg morphine sulphate ( p.o . ) at a 2-wk interval in a double-blind , r and omized , and counterbalanced order . PPI was measured 75 min after drug/placebo intake . The effects of morphine on mood were measured by the Adjective Mood Rating Scale and side-effects were assessed by the List of Complaints . Additionally , we administered a comprehensive neuropsychological test battery consisting of tests of the Cambridge Neuropsychological Test Automated Battery and the Rey Auditory Verbal Learning Test . Morphine significantly increased PPI without affecting startle reactivity or habituation . Furthermore , morphine selectively improved the error rate in an attentional set-shifting task but did not influence vigilance , memory , or executive functions . These results imply that the opioid system is involved in the modulation of PPI and attentional set-shifting in humans and they raise the question whether the opioid system plays a crucial role also in the regulation of PPI and attentional set-shifting in schizophrenia We investigated the association of the OPRM1 genotype with  long-term smoking cessation and  change in body mass index ( BMI ) following a smoking cessation attempt among smokers who attempted to quit using the nicotine replacement therapy ( NRT ) patch or placebo in a r and omized controlled trial , and were followed-up over an 8-year period following their initial cessation attempt . We also investigated possible sex differences in these relationships , given evidence for sex differences in smoking cessation and central opioid mechanisms , as well as some evidence for sex differences in response to NRT . Our results indicate that OPRM1 genotype may moderate the effect of  transdermal nicotine patch compared to placebo during active treatment , with a benefit of active NRT treatment evident in the OPRM1 AA genotype group only and those carrying one or more copies of the G allele demonstrating no benefit of active NRT versus placebo patch . Our results also indicate a sex difference in change in BMI at 8-year follow-up following a smoking cessation attempt , with ex-smokers demonstrating an increase in BMI , and this increase being greater in female subjects than in male subjects . We did not observe any association of OPRM1 genotype with change in BMI , although there was a trend for genotype to influence the observed sex difference in change in BMI over time . Future studies should attempt to replicate these findings , and investigate the relationship between both short- and long-term weight gain and smoking cessation and investigate possible mechanisms that may underlie these processes . Future studies should also investigate the role of OPRM1 genotype and smoking cessation on other appetitive and reward behaviours such as alcohol consumption AIM To examine whether Rasch modeling would yield a unidimensional withdrawal sensitivity measure correlating with factors associated with successful smoking cessation . DESIGN The psychometric Rasch modeling approach was applied to estimate an underlying latent construct ( withdrawal sensitivity ) in retrospective responses from 1644 smokers who reported quitting for 3 or more months at least once . SETTING Web-based , passcode-controlled self-administered computerized question naire . PARTICIPANTS R and omly selected convenience sample of 1644 adult members of an e-mail invitation-only web panel drawn from consumer data bases . MEASUREMENTS Lifetime Tobacco Use Question naire , assessing tobacco use across the life-span , including demographics and respondent ratings of the severity of withdrawal symptoms experienced in respondents ' first and most recent quit attempts lasting 3 or more months . FINDINGS Rasch-modeled withdrawal sensitivity was generally unidimensional and was associated with longer periods of smoking cessation . One latent variable accounted for 74 % of the variability in symptom scores . Rasch modeling with a single latent factor fitted withdrawal symptoms well , except for increased appetite , for which the fit was marginal . Demographic variables of education , gender and ethnicity were not related to changes in sensitivity . Correlates of greater withdrawal sensitivity in cessation attempts of at least 3 months included younger age at first quit attempt and indicators of tobacco dependence . CONCLUSION The relationship between tobacco dependence symptoms and Rasch-model withdrawal sensitivity defines further the relationship between sensitivity and dependence . The findings demonstrate the utility of modeling to create an individual-specific sensitivity measure as a tool for exploring the relationships among sensitivity , dependence and cessation OBJECTIVE Both age and gender are being increasingly recognized as important factors influencing CNS structure and function . However , there are relatively few data on actual neurochemical differences between the sexes in human subjects or on their interaction with age . One of the central neurotransmitter systems for which sex differences have been suggested by animal models and clinical human data is the opioid . In this study the authors examined age- and gender-associated variations in mu-opioid receptor binding with positron emission tomography ( PET ) . METHOD Healthy human subjects were studied with PET and the radiotracer [11C]carfentanil , a selective mu-opioid agonist .  Two separate subject groups were examined : one group of 24 men and 12 women was studied in a retrospective analysis of data , and a second group of 12 men and 18 women was recruited prospect ively and studied with a higher-resolution scanner .  RESULTS Mu-opioid receptor binding potential ( Bmax/Kd ) was found to increase with age in neocortical areas and the putamen . Sex differences , with higher mu-opioid binding in women , were observed in a number of cortical and subcortical areas . Gender-by-age interactions were observed in the thalamus and the amygdala ; in vivo mu-opioid binding declined in postmenopausal women to levels below those of men . CONCLUSIONS These data imply that both age and gender are important variables to consider in the interpretation of investigations of human function in which the opioid system plays a role . Also , women 's reproductive status ( reproductive age versus postmenopausal ) may influence the function of CNS opioid systems Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated , there is substantial variability among individuals in treatment response . We performed a systems-based c and i date gene study of 1295 single nucleotide polymorphisms ( SNPs ) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a  bupropion placebo-controlled  r and omized clinical trial . Putative functional variants were supplemented with tagSNPs within each gene . We used global tests of main effects and treatment interactions , adjusting the P-values for multiple correlated tests . An SNP ( rs2072661 ) in the 3′ UTR region of the β2 nicotinic acetylcholine receptor subunit ( CHRNB2 ) has an impact on abstinence rates at the end of treatment ( adjusted P = 0.01 ) and after a 6-month follow-up period ( adjusted P = 0.0002 ) . This latter P-value is also significant with adjustment for the number of genes tested . Independent of treatment at 6-month follow-up , individuals carrying the minor allele have substantially decreased the odds of quitting ( OR = 0.31 ; 95 % CI 0.18–0.55 ) . Effect of estimates indicate that the treatment is more effective for individuals with the wild-type ( OR = 2.14 , 95 % CI 1.20–3.81 ) compared with individuals carrying the minor allele ( OR = 0.83 , 95 % CI 0.32–2.19 ) , although this difference is only suggestive ( P = 0.10 ) . Furthermore , this SNP demonstrated a role in the time to relapse ( P = 0.0002 ) and an impact on withdrawal symptoms at target quit date ( TQD ) ( P = 0.0009 ) . Overall , while our results indicate strong evidence for CHRNB2 in ability to quit smoking , these results require replication in an independent sample We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs ( TASs ) . Reported TASs were common [ median risk allele frequency 36 % , interquartile range ( IQR ) 21%−53 % ] and were associated with modest effect sizes [ median odds ratio ( OR ) 1.33 , IQR 1.20–1.61 ] . Among 20 genomic annotation sets , reported TASs were significantly overrepresented only in nonsynonymous sites [ OR = 3.9 ( 2.2−7.0 ) , p = 3.5 × 10−7 ] and 5kb-promoter regions [ OR = 2.3 ( 1.5−3.6 ) , p = 3 × 10−4 ] compared to SNPs r and omly selected from genotyping arrays . Although 88 % of TASs were intronic ( 45 % ) or intergenic ( 43 % ) , TASs were not overrepresented in introns and were significantly depleted in intergenic regions [ OR = 0.44 ( 0.34−0.58 ) , p = 2.0 × 10−9 ] . Only slightly more TASs than expected by chance were predicted to be in regions under positive selection [ OR = 1.3 ( 0.8−2.1 ) , p = 0.2 ] . This new online re source , together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci , is well-suited to guide future investigations of the role of common variants in complex disease etiology Abilities to successfully quit smoking display substantial evidence for heritability in classic and molecular genetic studies . Genomewide association ( GWA ) studies have demonstrated single-nucleotide polymorphisms ( SNPs ) and haplotypes that distinguish successful quitters from individuals who were unable to quit smoking in clinical trial participants and in community sample s. Many of the subjects in these clinical trial sample s were aided by nicotine replacement therapy ( NRT ) . We now report novel GWA results from participants in a clinical trial that sought dose/response relationships for “ precessation ” NRT . In this trial , 369 European-American smokers were r and omized to 21 or 42 mg NRT , initiated 2 wks before target quit date s. Ten-week continuous smoking abstinence  was assessed on the basis of self-re 
    Output:
    
It appeared that A118 was more likely to increase susceptibility to smoking behaviors than 118 G , especially with regard to nicotine dependence , but less with smoking initiation and cessation .