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; 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.

Nonwillingness to Return to the Emergency Department and Nonattendance of Follow-Up Care Arrangements Following an Initial Suicide-Related Presentation.

Background: For people experiencing a suicidal crisis the emergency department (ED) is often the only option to find help. Aims: The aims of this study were (a) to identify predictors of patients' nonwillingness to return to the ED for help with a future suicidal crisis, and (b) whether nonwillingness to return was associated with follow-up appointment nonattendance. Method: This study utilized baseline data from the RESTORE online survey, and included 911 participants who had presented to an ED for suicidal crisis in the past 18 months, across participating local health districts in the Australian Capital Territory and New South Wales. Results: Patients who reported a more negative ED experience and longer triage wait times were less willing to return. Those who were less willing to return were also less likely to attend their follow-up appointment. Limitations: Due to the cross-sectional study design, causal inferences are not possible. Additionally, the self-report measures used are susceptible to recall bias. Conclusion: Patients' experience of service at EDs is a key indicator to drive improvement of patient outcomes for individuals experiencing a suicidal crisis.

Short report: Understanding the process of multilevel suicide prevention research trials.

This paper reviews process evaluations associated with multilevel suicide prevention research trials. Process evaluations can provide important information about how multilevel suicide prevention models are implemented, their mechanisms of impact, and the context and elements of implementation that mediate effectiveness. Out of 42 papers identified, only four met selection criteria for including a process evaluation. Of these four, there was large variation in the level of detail provided, and only two studies specifically focused on the process of implementing a multilevelsuicide prevention model. Future trials should include targeted process evaluation, which can benefit a range of knowledge users.

Experience of Health Care Services After a Suicide Attempt: Results from an Online Survey.

Failure to provide follow-up care after a suicide attempt is associated with increased risk of reattempt. This online survey examined the experiences of patients of the Australian health system after a suicide attempt. Just over half of the participants had a psychiatric assessment within 1 week of their attempt. Fewer than half believed they had been offered enough help. Low service satisfaction was associated with lower help-seeking intentions. Support for individuals who have made a suicide attempt needs to be enhanced, and an integrated approach to care is required, including improved referral pathways and staff attitudinal change.

Suicide prevention in Australian Aboriginal communities: a review of past and present programs.

A review of Aboriginal suicide prevention programs were conducted to highlight promising projects and strategies. A content analysis of gray literature was conducted to identify interventions reported to have an impact in reducing suicidal rates and behaviors. Most programs targeted the whole community and were delivered through workshops, cultural activities, or creative outlets. Curriculums included suicide risk and protective factors, warning signs, and mental health. Many programs were poorly documented and evaluations did not include suicidal outcomes. Most evaluations considered process variables. Results from available outcome evaluations suggest that employing a whole of community approach and focusing on connectedness, belongingness and cultural heritage may be of benefit. Despite the challenges, there is a clear need to evaluate outcomes if prevention is to be progressed.

What might interrupt men's suicide? Results from an online survey of men.

OBJECTIVES: Men are almost two times more likely to die by suicide than women, yet little research has focused on what is required to prevent suicide among men. This paper aims to investigate what factors interrupt suicidal behaviour in men, and to examine differences according to known suicide risk factors. SETTING: Australia. PARTICIPANTS: 251 Australian men aged 18 years and over who had made a suicide attempt 6-18 months prior to completing the survey. OUTCOMES: The survey canvassed the language men use to describe their depression and suicidality, warning signs, barriers to accessing help and what is needed to interrupt a suicide attempt. ORs and χ(2) were used to test for differences by age, geographic location and current depression severity. RESULTS: Of 299 men screened and eligible to participate, 251 completed all or part of the survey. Participants identified different words and warning signs for depression compared with suicidality. The most commonly endorsed barriers to accessing help were not wanting to burden others (66%) and having isolated themselves (63%). Men overwhelmingly endorsed 'I thought about the consequences for my family' as the factor which stopped a suicide attempt (67%). 'I need support from someone I really trust and respect' was also strongly endorsed. There were few differences by age, region or depression severity. CONCLUSIONS: Participants were able to identify signs, albeit often subtle ones, that they were becoming depressed or suicidal. Similarly, most were able to identify active strategies to interrupt this downward spiral. Men wanted others to notice changes in their behaviour, and to approach them without judgement.

Persistence of preference for a flavor presented in simultaneous compound with sucrose.

Rats exposed to a simultaneous compound of a flavor and sucrose subsequently exhibited a preference for the flavor over water. This preference persisted across repeated testing even though the flavor was presented in the absence of sucrose. The preference did, however, extinguish if the rats were hungry when trained or tested, or if they had been reexposed to sucrose between training and test. Though failing to extinguish the preference, presentation of the flavor outside the compound protected it from the effects of sucrose devaluation, indicating that these presentations extinguished the within-compound association between the flavor and sucrose. The authors conclude that the hedonic reaction elicited by sucrose imbues the flavor with the same hedonic properties, and these properties maintain the preference independently of the flavor-sucrose association.

Hepatitis C testing and status among opioid substitution treatment clients in New South Wales.

BACKGROUND: In Australia about half of the people who inject drugs (PWID) are hepatitis C (HCV) antibody positive (anti-HCV+). The prevalence among opioid substitution treatment (OST) clients specifically is unclear, despite OST clinics being a potential setting for HCV care. This study aimed to report the prevalence of HCV among a large sample of NSW OST clients, understand whether HCV testing is translating into knowledge of status, and identify the correlates of inaccurate self-reporting of HCV status. METHODS: Participants completed an interview that included self-reported HCV status. Participants also provided a blood sample that was tested for HCV IgG antibodies, and for viral load using a quantitative real-time reverse-transcriptase polymerase chain reaction. Valid interviews and viable blood sample were provided by 1,484 participants. Logistic regression modelling was used to identify independent predictors of knowledge of HCV antibody status. RESULTS: Overall, 84% of participants were anti-HCV+. Of these, 65% were RNA+. Four per cent of anti-HCV negative participants were RNA+. One-quarter of anti-HCV+ participants did not know their status or reported it incorrectly, compared with 14.5% of anti-HCV negative participants. CONCLUSION: The prevalence of HCV in this sample was higher than that found among other samples of people who inject drugs, suggesting the need for greater prevention efforts with OST clients. Anti-HCV+ individuals are less accurate at reporting their HCV status than those who are anti-HCV-. Inaccurate knowledge is associated with different variables for anti-HCV+ vs. anti-HCV- individuals. There are opportunities to improve knowledge of HCV status and to therefore improve health outcomes and reduce transmission among this at-risk population.

The effectiveness of a suicide prevention app for indigenous Australian youths: study protocol for a randomized controlled trial.

BACKGROUND: Indigenous Australian youth (aged 15 to 34) have up to four times the risk of suicide compared with their non-Indigenous counterparts. Barriers to help-seeking include shame, feared loss of autonomy and negative attitudes towards healthcare providers. The use of mobile devices and apps continues to rise amongst young people, thus presenting opportunities to utilize these aids in overcoming help-seeking barriers. Apps have been shown to assist in several health-related areas, including weight loss and smoking cessation, although no apps have as yet been evaluated for suicide prevention. Moreover, there is a lack of research that scientifically evaluates suicide prevention interventions within Indigenous communities. METHODS/DESIGN: In this study, a recently developed self-help app will be evaluated in a randomized controlled trial. The intervention is based on acceptance and commitment therapy and mindfulness-based cognitive behavioural therapy. It is aimed at participants who have suicidal thoughts but who are not actively suicidal. In total, 150 participants will be randomly allocated to the intervention-condition (N = 75) or to the wait-list control condition (N = 75). Questionnaires will be completed at baseline, post-test and 6 weeks follow-up. The primary outcome measure is a reduction in frequency and intensity of suicidal thoughts. Secondary outcome measures are the reduction of depression, anxiety and impulsivity. DISCUSSION: This study is the first to evaluate the effectiveness of a self-help app for suicidal thoughts amongst young Indigenous people. Several limitations and strengths of the design are discussed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000104752.

ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.

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.

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

Opioid dependence latent structure: two classes with differing severity?

AIMS: To examine the structure of illicit opioid abuse and dependence within an opioid dependent sample and its relationship to other clinical variables. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study of 1511 opioid dependent individuals recruited through opioid pharmacotherapy clinics in the Sydney area, Australia. MEASUREMENTS: 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. FINDINGS: 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. CONCLUSION: 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.

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.