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Genes encoding the opioid receptors (OPRM1, OPRD1 and OPRK1) are obvious candidates for involvement in risk for heroin dependence. Prior association studies commonly had samples of modest size, included limited single nucleotide polymorphism (SNP) coverage of these genes and yielded inconsistent results. Participants for the current investigation included 1459 heroin-dependent cases ascertained from maintenance clinics in New South Wales, Australia, 1495 unrelated individuals selected from an Australian sample of twins and siblings as not meeting DSM-IV criteria for lifetime alcohol or illicit drug dependence (non-dependent controls) and 531 controls ascertained from economically disadvantaged neighborhoods in proximity to the maintenance clinics. A total of 136 OPRM1, OPRD1 and OPRK1 SNPs were genotyped in this sample. After controlling for admixture with principal components analysis, our comparison of cases to non-dependent controls found four OPRD1 SNPs in fairly high linkage disequilibrium for which adjusted P values remained significant (e.g. rs2236857; OR 1.25; P=2.95×10(-4) ) replicating a previously reported association. A post hoc analysis revealed that the two SNP (rs2236857 and rs581111) GA haplotype in OPRD1 is associated with greater risk (OR 1.68; P=1.41×10(-5) ). No OPRM1 or OPRK1 SNPs reached more than nominal significance. Comparisons of cases to neighborhood controls reached only nominal significance. Our results replicate a prior report providing strong evidence implicating OPRD1 SNPs and, in particular, the two SNP (rs2236857 and rs581111) GA haplotype in liability for heroin dependence. Support was not found for similar association involving either OPRM1 or OPRK1 SNPs., (© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.)

Context: The genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging., Objective: To examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs) with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations., Design: Case-control genetic association study that included 2 control groups (lacking an established optimal control group)., Setting: Semistructured psychiatric interviews., Participants: A total of 1459 Australian cases ascertained from opioid replacement therapy clinics, 531 neighborhood controls ascertained from economically disadvantaged areas near opioid replacement therapy clinics, and 1495 unrelated Australian Twin Registry controls not dependent on alcohol or illicit drugs selected from a twin and family sample., Main Outcome Measure: Lifetime heroin dependence., Results: Comparison of cases with Australian Twin Registry controls found minimal evidence of association for all chromosome 11 cluster SNPs (P ≥ .01); a similar comparison with neighborhood controls revealed greater differences (P ≥ 1.8 × 10(-4)). Comparing cases (n = 1459) with the subgroup of neighborhood controls not dependent on illicit drugs (n = 340), 3 SNPs were significantly associated (correcting for multiple testing): ANKK1 SNP rs877138 (most strongly associated; odds ratio = 1.59; 95% CI, 1.32-1.92; P = 9.7 × 10(-7)), ANKK1 SNP rs4938013, and TTC12 SNP rs7130431. A similar pattern of association was observed when comparing illicit drug-dependent (n = 191) and nondependent (n = 340) neighborhood controls, suggesting that liability likely extends to nonopioid illicit drug dependence. Aggregate heroin dependence risk associated with 2 SNPs, rs877138 and rs4492854 (located in NCAM1), varied more than 4-fold (P = 2.7 × 10(-9) for the risk-associated linear trend)., Conclusions: Our results provide further evidence of association for chromosome 11 gene cluster SNPs with substance dependence, including extension of liability to illicit drug dependence. Our findings highlight the necessity of considering drug exposure history when selecting control groups for genetic investigations of illicit drug dependence.

Introduction and Aims: To examine differences in the characteristics and histories of male and female dependent heroin users, and in the clinical characteristics associated with multiple substance dependence diagnoses., Design and Methods: 1513 heroin dependent participants underwent an interview covering substance use and dependence, psychiatric history, child maltreatment, family background, adult violence and criminal history. Family background, demographic and clinical characteristics were analysed by sex. Ordinal regression was used to test for a relationship between number of substance dependence diagnoses and other clinical variables., Results: Women were more likely to experience most forms of child maltreatment, to first use heroin with a boyfriend or partner, to experience ongoing adult violence at the hands of a partner, and to have a poorer psychiatric history than men. Males had more prevalent lifetime substance dependence diagnoses and criminal histories and were more likely to meet the criteria for ASPD. Predictors of multiple substance dependence diagnoses for both sexes were mental health variables, antisocial behaviour, childhood sexual abuse, victim of adult violence, younger age at first cannabis use and overdose. As the number of dependence diagnoses increased, clinical and behavioural problems increased. Childhood emotional neglect was related to increasing dependence diagnoses for females but not males, whereas PTSD was a significant predictor for males but not females., Discussion and Conclusions: Mental health problems, other substance dependence, childhood and adult trauma were common in this sample, with sex differences indicating different treatment needs and possible different pathways to heroin dependence for men and women., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

To examine the structure of illicit opioid abuse and dependence within an opioid dependent sample and its relationship to other clinical variables. A cross-sectional study of 1511 opioid dependent individuals recruited through opioid pharmacotherapy clinics in the Sydney area, Australia. A face-to-face structured interview covering substance use and dependence, psychiatric history, child maltreatment, family background, adult violence and criminal history. Dimensional, latent class and factor mixture models were fit to the opioid abuse and dependence data. Classes were then compared on a range of demographic and clinical covariates. A two-class, one-factor model provided the best fit of all the models tested. The two classes differed with respect to endorsement probabilities on a range of abuse and dependence criteria, and also with respect to the odds of other drug dependence diagnoses, antisocial personality disorder and non-fatal opioid overdose. Within-class severity was associated with similar variables: other drug dependence, borderline personality disorder and opioid overdose. In an in-treatment, opioid-dependent sample, there appears to be two classes of individuals exhibiting distinct patterns of abuse and dependence criteria endorsement and to differ on externalizing but not internalizing disorders. This study provides preliminary evidence that the proposed DSM-V opioid use disorder distinction between moderate and severely dependent people is valid. Class one participants were not only more severely dependent, but had greater odds for opioid overdoses, other drug dependence and antisocial personality disorder. [ABSTRACT FROM AUTHOR]