Defining nicotine dependence for genetic research: evidence from Australian twins

Background. Whether current criteria used to define nicotine dependence are informative for genetic research is an important empirical question. The authors used items of the DSM-IV and of the Heaviness of Smoking Index to characterize the nicotine dependence phenotype and to identify salient symptoms in a genetically informative community sample of Australian young adult female and mate twins. Method. Phenotypic and genetic factor analyses were performed on nine dependence symptoms (the seven DSM-IV substance dependence criteria and the two Heaviness of Smoking Index (HSI) items derived from the Fagerstrom Tolerance Questionnaire, time to first cigarette in the morning and number of cigarettes smoked per day). Phenotypic and genetic analyses were restricted to ever smokers. Results. Phenotypic nicotine dependence symptom covariation was best captured by two factors with a similar pattern of factor loadings for women and men. In genetic factor analysis item covariation was best captured by two genetic but one shared environmental factor for both women and men; however, item factor loadings differed by gender. All nicotine dependence symptoms were substantially heritable, except for the DSM-IV criterion of 'giving up or reducing important activities in order to smoke', which was weakly familial. Conclusions. The salient behavioral indices of nicotine dependence are similar for women and men. DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting and HSI items time to first cigarette in the morning and number of cigarettes smoked per day may represent the most highly heritable symptoms of nicotine dependence for both women and men.

Course of substance misuse and daily tobacco use in first-episode psychosis

Background: Study of the course of substance misuse and daily tobacco use in first-episode psychosis may enhance detection and treatment of these substance-related problems. Methods: This 15-month follow-up study examined the course of substance misuse and daily tobacco use in 103 individuals treated for first-episode psychosis. Results: Three-quarters (72.6%) of patients with lifetime substance misuse, or half (51.5%) of all patients, continued substance misuse (primarily cannabis) during the 15-month follow-up period. There was a significant reduction in the rate of any substance misuse (70.9% versus 53.4%) but not daily tobacco use (76.7% versus 75.7%) between baseline and 15-month follow-up. Patients who continued substance misuse showed a significant reduction in the severity and frequency of substance use between baseline and follow-up. Patients who continued substance misuse were more likely to be younger, male and single, less likely to have completed secondary school, and more likely to have had more severe cannabis use prior to entry to treatment compared to patients who ceased substance misuse. Discussion: A significant proportion of young patients treated for first-episode psychosis are at risk of mental and physical health problems associated with substance misuse and/or regular tobacco use. (c) 2005 Elsevier B.V. All rights reserved.

Images of desire: Cognitive models of craving

Cognitive modelling of phenomena in clinical practice allows the operationalisation of otherwise diffuse descriptive terms such as craving or flashbacks. This supports the empirical investigation of the clinical phenomena and the development of targeted treatment interventions. This paper focuses on the cognitive processes underpinning craving, which is recognised as a motivating experience in substance dependence. We use a high-level cognitive architecture, Interacting Cognitive Subsystems (ICS), to compare two theories of craving: Tiffany's theory, centred on the control of automated action schemata, and our own Elaborated Intrusion theory of craving. Data from a questionnaire study of the subjective aspects of everyday desires experienced by a large non-clinical population are presented. Both the data and the high-level modelling support the central claim of the Elaborated Intrusion theory that imagery is a key element of craving, providing the subjective experience and mediating much of the associated disruption of concurrent cognition.

Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders

Objectives The aims of the study were to describe the prevalence and associations of mental health disorder (MHD) among a cohort of HIV-infected patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to examine whether antiretroviral therapy use or mortality was influenced by MHD (defined as a record of service provision by psychiatric services on the Victorian Psychiatric Case Register). It was hypothesized that HIV-positive individuals with MHD would have poorer treatment outcomes, reduced responses to highly active antiretroviral therapy (HAART) and increased mortality compared with those without MHD. Methods This is a retrospective cohort of 2981 individuals (73% of the Victorian population diagnosed with HIV infection) captured on an HIV database which was electronically matched with the public Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system psychiatry service provision). The prevalence, dates and recorded specifics of mental health disorders at the time of the electronic match on 1 June 2000 are described. The association with recorded MHD, gender, age, AIDS illness, HIV exposure category, duration and type of antiviral therapy, treatment era (prior to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and mortality at 1 September 2001 was assessed. Results Five hundred and twenty-five individuals (17.6% of the Victorian HIV-positive population) were recorded with MHD, most frequently coded as attributable to substance dependence/abuse or affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis. Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for both psychiatric and nonpsychiatric illness were more frequent in those with MHD (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. Conclusions MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.

The genetics of alcohol intake and of alcohol dependence

Background: Because alcohol has multiple dose-dependent consequences, it is important to understand the causes of individual variation in the amount of alcohol used. The aims of this study were to assess the long-term repeatability and genetic or environmental causes of variation in alcohol intake and to estimate the degree of overlap with causes of susceptibility to alcohol dependence. Methods: Data were used from three studies conducted between 1980 and 1995 on volunteer adult male and female Australian twin subjects. In each study, alcohol intake was reported both as quantity X frequency and as past-week data. Repeatability was calculated as correlations between occasions and between measures, and the effects of genes and environment were estimated by multivariate model fitting to the twin pair repeated measures of alcohol use. Relationships between mean alcohol use and the lifetime history of DSM-III-R alcohol dependence were tested by bivariate model fitting. Results: Repeatability of the alcohol intake measures was between 0.54 and 0.85, with the highest repeatability between measures within study and the lowest repeatability between the first and last studies. Reported alcohol consumption was mainly affected by genetic factors affecting all times of study and by nonshared environmental factors (including measurement error) unique to each time of study. Genes that affect alcohol intake do affect alcohol dependence, but genetic effects unique to dependence are also significant; environmental effects are largely unique to either intake and dependence. Conclusions: Nearly all the repeatable component of variation in alcohol intake is due to genetic effects. Genes affecting intake also affect dependence risk, but there are other genes that affect dependence alone. Studies aiming to identify genes that affect alcohol use disorders need to test loci and candidate genes against both phenotypes.

Major Depressive Disorder, Suicidal Ideation, and Suicide Attempt in Twins Discordant for Cannabis Dependence and Early-Onset Cannabis Use

Background: Previous research has reported both a moderate degree of comorbidity between cannabis dependence and major depressive disorder (MDD) and that early-onset cannabis use is associated with increased risks for MDD. Objective: To examine whether associations between both lifetime cannabis dependence and early cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist after controlling for genetic and/or shared environmental influences. Design: Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence and those discordant for early cannabis use. Setting: General population sample of twins (median age, 30 years). Participants: Two hundred seventy-seven same-sex twin pairs discordant for cannabis dependence and 311 pairs discordant for early-onset cannabis use (before age 17 years). Main Outcome Measures: Self-report measures of DSM-IV-defined lifetime MDD, suicidal ideation, and suicide attempt. Results: Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non-cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs. Conclusions: Comorbidity between cannabis dependence and MDD likely arises through shared genetic and environmental vulnerabilities predisposing to both outcomes. In contrast, associations between cannabis dependence and suicidal behaviors cannot be entirely explained by common predisposing genetic and/or shared environmental predispositions. Previously reported associations between early-onset cannabis use and subsequent MDD likely reflect shared genetic and environmental vulnerabilities, although it remains possible that early-onset cannabis use may predispose to suicide attempt.

Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47 % (95 % CI 28-55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0 % (95 % CI 0-14) to shared environmental factors, and 53 % (95 % CI 45-63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.

The contribution of research to Australian policy responses to heroin dependence 1990-2001: a personal retrospection

Periodic public concern about heroin use has been a major driver of Australian drug policy in the four decades since heroin use was first reported. The number of heroin-dependent people in Australia has increased from several hundreds in the late 1960s to around 100000 by the end of the 1990s. In this paper I do the following: (1) describe collaborative research on heroin dependence that was undertaken between 1991 and 2001 by researchers at the National Drug and Alcohol Research Centre: (2) discuss the contribution that this research may have made to the formulation of policies towards the treatment of heroin dependence during a period when the policy debate crystallized around the issue of whether or not Australia should conduct a controlled trial of heroin prescription; and (3) reflect on the relationships between research and policy-making in the addictions field, specifically on the roles of investigator-initiated and commissioned research, the interface between researchers, funders and policymakers: and the need to be realistic about the likely impact of research on policy and practice.

Beating the urge: Implications of research into substance-related desires

Despite the advent of improved pharmacological treatments to alleviate substance-related desires, psychological approaches will continue to be required. However, the current psychological treatment that most specifically focuses on desires and their management-cue exposure (CE)-has not lived up to its original promise. This paper argues that current psychological approaches to desire do not adequately incorporate our knowledge about the factors that trigger, maintain, and terminate episodes of desire. It asserts that the instigation and maintenance of desires involve both associative and elaborative processes. Understanding the processes triggering the initiation of intrusive thoughts may assist in preventing some episodes, but occasional intrusions will be inevitable. A demonstration of the ineffectiveness of thought suppression may discourage its use as a coping strategy for desire-related intrusions, and mindfulness meditation plus cognitive therapy may help in accepting their occurrence and letting them go. Competing tasks may be used to reduce elaboration of desires, and competing sensory images may have particular utility. The application of these procedures during episodes that are elicited in the clinic may allow the acquisition of more effective strategies to address desires in the natural environment. (C) 2004 Elsevier Ltd. All rights reserved.

Alcohol dependence: the impact of cognitive behaviour therapy with or without naltrexone on subjective health status

Objectives: To examine the health-related quality of life of alcohol-dependent patients across a 12-week cognitive behaviour treatment (CBT) program and identify whether the patient selection of the anticraving medication naltrexone further enhanced these outcomes. Method: One hundred and thirty-six consecutive alcohol-dependent subjects voluntarily participated and were offered naltrexone, of which 73 (54%) participants declined medication. A matched design was used. Of the 136 subjects, 86 (43 naltrexone and CBT; 43 CBT only) could be individually matched (blind to outcome measures) for gender, age, prior alcohol detoxification and dependence severity. Measures of health status and mental health wellbeing included the Rand Corporation Medical Outcomes Short Form 36 Health Survey (SF-36) and the General Health Questionnaire (GHQ-28). Results: Pre-treatment, all had SF-36 and GHQ-28 scores markedly below national norms. Post-treatment, significant improvement in seven of the eight SF-36 subscales and all of the GHQ-28 subscales occurred, approximating national normative levels. Patients in the CBT + naltrexone group were significantly more likely to have increased days abstinent (p = 0.002) and to complete the program abstinent (p = 0.051). The adjunctive use of naltrexone did not provide additional benefit as reflected in SF-36 and GHQ-28 scores, beyond CBT alone. Conclusions: Patients who completed the CBT-based treatment program reported significant improvements in self-reported health status (SF-36) and wellbeing (GHQ-28). The adjunctive use of naltrexone demonstrated no additional improvement in these measures.

The role of drinking restraint in alcohol dependence: validation of the temptation and restraint inventory in an alcohol dependent sample

Objective: The Temptation and Restraint Inventory (TRI) is commonly used to measure drinking restraint in relation to problem drinking behavior. However, as yet the TRI has not been validated in a clinical group with alcohol dependence. Method: Male (n = 111) and female (n = 57) inpatients with DSM-IV diagnosed alcohol dependence completed the TRI and measures of problem drinking severity, including the Alcohol Dependence Scale and the quantity, frequency and week total of alcohol consumed. Results: The factor structure of the TRI was replicated in the alcohol dependent sample. Cognitive Emotional Preoccupation (CEP), one of the two higher order factors of the TRI, demonstrated sound predictive power toward all dependence severity indices. The other higher order factor, Cognitive Behavioral Control (CBC), was related to frequency of drinking. There was limited support for the CEP/CBC interactional model of drinking restraint. Conclusions: Although the construct validity of the TRI was sound, the measure appears more useful in understanding the development, maintenance and severity of alcohol-related problems in nondependent drinkers. The TRI may show promise in detecting either continuous drinking or heavy episodic type dependent drinkers.

Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD)

Aims The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment. Design A longitudinal study based on data from 12 trials included in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Participants and settings A total of 1.244 heroin users and methadone patients treated in hospital, community and GP settings. Intervention Six trials included detoxification; all included treatment with methadone, buprenorphine, levo-alpha-acetyl-methadol (LAAM) or naltrexone. Findings During 394 person-years of observation, 79 SAEs of 28 types were recorded. Naltrexone participants experienced 39 overdoses per 100 person-years after leaving treatment (44% occurred within 2 weeks after stopping naltrexone). This was eight times the rate recorded among participants who left agonist treatment. Rates of all other SAEs were similar during treatment versus out of treatment, for both naltrexone-treated and agonist-treated participants. Five deaths occurred, all among participants who had left treatment, at a rate of six per 100 person-years. Total SAE rates during naltrexone and agonist treatments were similar (20, 14 per 100 person-years, respectively). Total SAE and death rates observed among participants who had left treatment were three and 19 times the corresponding rates during treatment. Conclusions Individuals who leave pharmacotherapies for opioid dependence experience higher overdose and death rates compared with those in treatment. This may be due partly to a participant self-selection effect rather than entirely to pharmacotherapy being protective. Clinicians should alert naltrexone treatment patients in particular about heroin overdose risks. Duty of care may extend beyond cessation of dosing.