Fiona Shand

Sex differences amongst dependent heroin users: histories, clinical characteristics and predictors of other substance dependence.

INTRODUCTION AND AIMSnTo 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.nnnDESIGN AND METHODSn1513 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.nnnRESULTSnWomen 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.nnnDISCUSSION AND CONCLUSIONSnMental 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.

Association of OPRD1 polymorphisms with heroin dependence in a large case-control series

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; Pu2003=u20032.95u2003×u200310−4) 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; Pu2003=u20031.41u2003×u200310−5). 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.

ANKK1, TTC12, and NCAM1 Polymorphisms and Heroin Dependence: Importance of Considering Drug Exposure

CONTEXTnThe genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging.nnnOBJECTIVEnTo 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.nnnDESIGNnCase-control genetic association study that included 2 control groups (lacking an established optimal control group).nnnSETTINGnSemistructured psychiatric interviews.nnnPARTICIPANTSnA 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.nnnMAIN OUTCOME MEASUREnLifetime heroin dependence.nnnRESULTSnComparison 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).nnnCONCLUSIONSnOur 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.

Real-time monitoring of Schedule 8 medicines in Australia: evaluation is essential.

A real-time reporting system for controlled drugs may improve the safety of Schedule 8 medicines

Evidence of CNIH3 involvement in opioid dependence

Opioid dependence, a severe addictive disorder and major societal problem, has been demonstrated to be moderately heritable. We conducted a genome-wide association study in Comorbidity and Trauma Study data comparing opioid-dependent daily injectors (N=1167) with opioid misusers who never progressed to daily injection (N=161). The strongest associations, observed for CNIH3 single-nucleotide polymorphisms (SNPs), were confirmed in two independent samples, the Yale-Penn genetic studies of opioid, cocaine and alcohol dependence and the Study of Addiction: Genetics and Environment, which both contain non-dependent opioid misusers and opioid-dependent individuals. Meta-analyses found five genome-wide significant CNIH3 SNPs. The A allele of rs10799590, the most highly associated SNP, was robustly protective (P=4.30E-9; odds ratio 0.64 (95% confidence interval 0.55–0.74)). Epigenetic annotation predicts that this SNP is functional in fetal brain. Neuroimaging data from the Duke Neurogenetics Study (N=312) provide evidence of this SNP’s in vivo functionality; rs10799590 A allele carriers displayed significantly greater right amygdala habituation to threat-related facial expressions, a phenotype associated with resilience to psychopathology. Computational genetic analyses of physical dependence on morphine across 23 mouse strains yielded significant correlations for haplotypes in CNIH3 and functionally related genes. These convergent findings support CNIH3 involvement in the pathophysiology of opioid dependence, complementing prior studies implicating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate system.

Opioid dependence latent structure : two classes with differing severity?

AIMSnTo examine the structure of illicit opioid abuse and dependence within an opioid dependent sample and its relationship to other clinical variables.nnnDESIGN, SETTING AND PARTICIPANTSnA cross-sectional study of 1511 opioid dependent individuals recruited through opioid pharmacotherapy clinics in the Sydney area, Australia.nnnMEASUREMENTSnA 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.nnnFINDINGSnA 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.nnnCONCLUSIONnIn 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.

The effect of comorbid substance use disorders on treatment outcome for anxiety disorders.

This study examined the impact of concurrent substance use disorders (SUDs) on outcomes for psychotherapy targeting anxiety disorders. Study 1 (N=484) sought to determine the prevalence of SUDs in a sample referred to a community anxiety disorders clinic, as well as the impact of comorbid SUDs on outcomes for a subsample (n=200) completing cognitive behavior therapy (CBT). Around one-quarter (22-29%) of patients with one or two anxiety disorders met criteria for at least one SUD, but this rate was substantially higher (46%) for patients with three anxiety disorders. Concurrent SUDs were associated with higher levels of anxiety but not depression or stress, compared to those without a SUD. However, concurrent SUDs did not moderate treatment outcomes. Study 2 (N=103) focused on the impact of alcohol use on diagnosis-specific symptom measures and generic measures of distress and disability, following a course of CBT for panic disorder or social phobia. Pre-treatment alcohol use did not predict changes in panic symptoms, performance anxiety, distress, or disability, but it did predict changes in social interaction anxiety. Problem drinking per se did not have any predictive utility in terms of treatment outcome. These findings suggest that clinicians treating patients for a primary anxiety disorder and concurrent SUD can be relatively optimistic about treatment outcomes.

Estimating the proportion of prescription opioids that is consumed by people who inject drugs in Australia

INTRODUCTION AND AIMSnTo estimate the contribution that people who inject drugs (PWID) make to population-level use of prescription opioids in Australia.nnnDESIGN AND METHODSnData on prescriptions of oxycodone, morphine and methadone tablets were obtained for New South Wales, Victoria, Tasmania and Queensland, and time series analyses used to characterise the trends from 2002 to 2010. Estimates of the number of PWID were combined with data on their levels, frequency and typical doses of morphine, methadone tablet (only prescribed in Australia for pain) and oxycodone from 2004 to 2010. Estimated consumption per 1000 PWID and per 1000 persons aged 20-69 years was contrasted and the proportion of total consumption accounted for by PWID estimated.nnnRESULTSnMorphine prescribing declined; oxycodone prescribing increased. PWID had far higher rates of prescription opioid consumption (defined daily doses per 1000) than the general population. Tasmania had highest use of prescribed opioids. PWID contribution to morphine consumption in Tasmania increased to 28% (range 22-37%) in 2010; elsewhere, PWID contribution was lower (midpoints of 2-12%, 2010). Methadone tablet use was less elevated compared with the general population. With the exception of Tasmania, PWID were estimated to consume less than 5% of oxycodone.nnnDISCUSSION AND CONCLUSIONSnPWID use prescription opioids at high levels and can account for a significant proportion of consumption. Increased oxycodone prescribing in Australia has not been driven by PWID. Opioid substitution therapy and other effective treatments need to be more available and attractive to PWID.

Prevalence and correlates of suicidal thoughts and suicide attempts in people prescribed pharmaceutical opioids for chronic pain

Objectives:The main objectives of the paper were (1) to examine the prevalence of suicidality in a large community-based chronic pain sample taking prescribed opioids for chronic pain; and (2) to examine general and pain-specific factors that predict such ideation, and the transition from ideation to making a suicide attempt (ideation-to-action). Materials and Methods:Baseline data from the Pain and Opioids IN Treatment (POINT) study with a cohort of 1514 community-based people prescribed opioids for chronic noncancer pain across Australia. Results:Past 12-month suicidal ideation was reported by 36.5% of the cohort and 16.4% had made a lifetime suicide attempt (2.5% in the last 12 mo), after the onset of their pain condition. Suicidal ideation in the past 12 months was independently associated with a past suicide attempt [adjusted odds ratio (AOR)=4.82; 95% confidence interval, 2.43-9.56] and past 12-month depression (AOR=4.07, 95% confidence interval, 1.88-8.78). Only a lower pain self-efficacy score was independently associated with past 12-month ideation-to-action (AOR=0.98, 95%CI0.88-0.99). Notably, only general-suicide risk factors were associated with 12-month suicidal ideation; but for past year ideation-to-action, pain-specific factors also had independent associations. Discussion:The study is one of the first to comprehensively examine general and pain-specific risk factors for suicidality in a large chronic pain sample in which suicidal ideation was common. A low pain self-efficacy score was the only factor independently associated past 12-month ideation-to-action.

Predictors of social anxiety in an opioid dependent sample and a control sample.

Compared to other mental health problems, social anxiety is under-acknowledged amongst opioid dependent populations. This study aimed to assess levels of social anxiety and identify its predictors in an opioid dependent sample and a matched control group. Opioid dependent participants (n=1385) and controls (n=417) completed the Social Interaction Anxiety Scale (SIAS), the Social Phobia Scale (SPS) and a diagnostic interview. Regression analyses were used to test a range of predictors of social anxiety. Opioid dependent cases had higher mean scores on both scales compared to controls. Predictors of social anxiety centred on emotional rejection in childhood, either by parents or peers. For opioid dependent cases, but not controls, lifetime non-opioid substance dependence (cannabis, sedatives, and tobacco) was associated with higher levels of social anxiety. However, much of the variance in social anxiety remains unexplained for this population.