Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake markers

Background: Alcohol increases body iron stores. Alcohol and iron may increase oxidative stress and the risk of alcohol-related liver disease. The relationship between low or safe levels of alcohol use and indices of body iron stores, and the factors that affect the alcohol-iron relationship, have not been fully characterized. Other aspects of the biological response to alcohol use have been reported to depend on iron status. Methods: We have measured serum iron, transferrin, and ferritin as indices of iron stores in 3375 adult twin subjects recruited through the Australian Twin Registry. Information on alcohol use and dependence and smoking was obtained from questionnaires and interviews. Results: Serum iron and ferritin increased progressively across classes of alcohol intake. The effects of beer consumption were greater than those of wine or spirits. Ferritin concentration was significantly higher in subjects who had ever been alcohol dependent. There was no evidence of interactions between HFE genotype or body mass index and alcohol. Alcohol intake-adjusted carbohydrate-deficient transferrin was increased in women in the lowest quartile of ferritin results, whereas adjusted gamma -glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase values were increased in subjects with high ferritin. Conclusions: Alcohol intake at low level increases ferritin and, by inference, body iron stores. This may be either beneficial or harmful, depending on circumstances. The response of biological markers of alcohol intake can be affected by body iron stores; this has implications for test sensitivity and specificity and for variation in biological responses to alcohol use.

Adherence with naltrexone prescription advice in hospital outpatient alcohol rehabilitation programme

Background: The anti-craving drug, naltrexone, is used as a pharmacotherapeutic adjunct in the treatment of alcohol dependence. In addictive disorders, compliance issues remain central. There are limited data on compliance with naltrexone treatment regimens within formalized rehabilitation programs and even less data that identifies factors that have an impact on this. Objective: To study patient adherence to naltrexone medication regimens and examine whether patients' reported pre-treatment alcohol use, dependence severity and measures of psychological health are predictive of medication compliance. Method: Fifty outpatients meeting DSM IV criteria for alcohol dependence enrolled in 12-week rehabilitation programme. This included cognitive behavioural therapy (CBT) and naltrexone, 50 mg orally daily. Measures included: pharmacy prescription pick-up including number of tablets dispensed, programme attendance and patient pre-treatment alcohol use variables. Measures of psychological health included somatic symptoms, anxiety, social dysfunction and depression as measured by the General Health Questionnaire (GHQ-28). Results: Classifying the sample into compliant (greater than or equal to 90% medication pick-up) and less compliant groups, 66% of subjects were naltrexone-compliant. Pre-treatment alcohol use variables were not predictive of compliance. Although social dysfunction and depression tended towards poorer prescription filling, measures of psychological distress (GHQ-28) did not identify factors predictive of medication non-compliance. One patient withdrew from treatment because of naltrexone-induced dysphoria. Conclusion: Patients with alcohol dependence demonstrated high levels of anti-craving medication compliance, good rehabilitation programme participation and favourable outcomes. Naltrexone was well tolerated. Medication compliance in this study group compared well with those of other hospital populations with chronic disorders. Factors predictive of anti-craving medication compliance in alcohol dependence require further study.

Outpatient cognitive behavioural therapy programme for alcohol dependence impact of naltrexone use on outcome

Objective: Cognitive-behavioural therapy (CBT) has been effectively used in the treatment of alcohol dependence. Clinical studies report that the anticraving drug naltrexone, is a useful adjunct to treatment. Currently, few data are available on the impact of adding this medication to programmes in more typical, outpatient, and rehabilitation settings. The objective of this study was to examine the impact on outcome of adding naltrexone to an established outpatient alcohol rehabilitation program which employed CBT. Method: Fifty patients participated in an established 12-week, outpatient, 'contract'-based alcohol abstinence programme which employed CBT. They also received naltrexone 50 mg orally daily (CBT + naltrexone). Outcomes were compared with 50 historical, matched controls, all of whom participated in the same programme without an anticraving medication (CBT alone). All patients met DSM-IV criteria for alcohol dependence. Results: Programme attendance across the eight treatment sessions was lower in the CBT alone group (p < 0.001). Relapse to alcohol use occurred sooner and more frequently in the CBT alone group (p < 0.001). Rehabilitation programme completion at 12 weeks was 88% (CBT + naltrexone) compared with 36% for (CBT alone) (p < 0.001). Alcohol abstinence at 12 weeks was 76% (CBT + naltrexone) compared with 18% (CBT alone) (p < 0.001). Conclusion: When employing the same outpatient rehabilitation programme and comparing outcomes using matched historical controls, the addition of naltrexone substantially improves programme attendance, programme completion and reported alcohol abstinence. In a typical outpatient programme, naltrexone addition was associated with significantly improved programme participation, better outcomes and was well tolerated.

Personality and the genetic risk for alcohol dependence

The extent to which the genetic risk for alcohol dependence (AD) and conduct disorder (CD) and their common genetic risk overlap with genetic factors contributing to variation in dimensions of personality was examined in a study of 6,453 individuals from 3,383 adult male and female same-sex and unlike-sex twin pairs from the Australian Twin Registry. The associations between the personality dimensions of positive emotionality, negative emotionality, and AD and CD risk were modest. whereas the associations between behavioral undercontrol and AD and CD risk were substantially higher. Genetic influences contributing to variation in behavioral undercontrol accounted for about 40% of the genetic variation in AD and CD risk and about 90% of the common genetic risk for AD and CD. These results suggest that genetic factors contributing to variation in dimensions of personality, particularly behavioral undercontrol. account for a substantial proportion of the genetic diathesis for AD and most of the common genetic diathesis for AD and CD among both men and women.

Identification of residues which regulate activity of the STE20-related kinase hMINK

Activity of the STE20-related kinase hMINK was investigated. hMINK was expressed widely, though not ubiquitously, in human tissues: highest levels being found in haematopoietic tissues but also in brain, placenta, and lung. Mutagenesis revealed that T-191. and Y-193 in the substrate recognition loop of the catalytic domain were critical for kinase activity against exogenous substrates and autophosphorylation. A mutation on T-187 showed reduced enzymatic activity against exogenous substrates but retained autophosphorylationactivity. Phosphorylation was confirmed by the use of a phospho-specific T-187 antibody. hMINK activated the JNK signal transduction pathway and optimal JNK activation occurred when the C-terminus was deleted. In addition, overexpression of the C-terminal domain devoid of kinase activity also resulted in significant activation of the JNK pathway. These data suggest that hMINK requires an activation step that dissociates the C terminal, thereby freeing the catalytic domain to interact with substrates. Models for receptor-mediated activation of hMINK are discussed. (C) 2002 Elsevier Science (USA). All rights reserved.

Effects of dopamine receptor D4 variation on alcohol and tobacco use and on novelty seeking: Multivariate linkage and association analysis

The dopamine D4 receptor gene contains a polymorphic sequence consisting of a variable number of 48-base-pair (bp) repeats, and there have been a number of reports that this polymorphism is associated with variation in novelty seeking or in substance abuse and addictive behaviors. In this study we have assessed the linkage and association of DRD4 genotype with novelty seeking, alcohol use, and smoking in a sample of 377 dizygotic twin pairs and 15 single twins recruited from the Australian Twin Registry (ATR). We found no evidence of linkage or association of the DRD4 locus with any of the phenotypes. We made use of repeated measures for some phenotypes to increase power by multivariate genetic analysis, but allelic effects were still non-significant. Specifically, it has been suggested that the DRD4 7-repeat allele is associated with increased novelty seeking in males but we found no evidence for this, despite considerable power to do so. We conclude that DRD4 variation does not have an effect on use of alcohol and the problems that arise from it, on smoking, or on novelty seeking behavior. (C) 2003 Wiley-Liss, Inc.

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.

Paradoxical association between smoking and olfactory identification in psychosis versus controls

Objective: Deficits in olfactory identification have been demonstrated in patients with schizophrenia. This study examined the interaction between smoking and olfactory identification in patients with psychotic disorders versus well controls. Method: Olfactory identification was assessed in three groups of subjects using the University of Pennsylvania Smell Identification Test (UPSIT). Sixteen patients with affective psychoses, 22 patients with nonaffective psychoses, and 21 well controls were tested. Results: There was a significant interaction between diagnostic classification (patient or control) and smoking. Patients who were smokers scored higher on the UPSIT than non-smokers, while controls who were smokers scored lower than non-smokers. Conclusions: Smoking may have a 'normalising' effect on olfactory identification in some patients with psychosis. Further studies are needed to examine the relationship between psychosis, olfactory identification and the effects of nicotine.

Assortative Mating for Cigarette Smoking and for Alcohol Consumption in Female Australian Twins and their Spouses

Background Non-random mating affects population variation for substance use and dependence. Developmentally, mate selection leading to positive spousal correlations for genetic similarity may result in increased risk for substance use and misuse in offspring. Mate selection varies by cohort and thus, assortative mating in one generation may produce marked changes in rates of substance use in the next. We aim to clarify the mechanisms contributing to spousal similarity for cigarette smoking and alcohol consumption. Methods Using data from female twins and their male spouses, we fit univariate and bivariate twin models to examine the contribution of primary assortative mating and reciprocal marital interaction to spousal resemblance for regular cigarette smoking and nicotine dependence, and for regular alcohol use and alcohol dependence. Results We found that assortative mating significantly influenced regular smoking, regular alcohol use, nicotine dependence and alcohol dependence. The bivariate models for cigarette smoking and alcohol consumption also highlighted the importance of primary assortative mating on all stages of cigarette smoking and alcohol consumption, with additional evidence for assortative mating across the two stages of alcohol consumption. Conclusions Women who regularly used, and subsequently were dependent on cigarettes or alcohol were more likely to marry men with similar behaviors. After mate selection had occurred, one partner's cigarette or alcohol involvement did not significantly modify the other partner's involvement with these psychoactive substances.

Is cannabis use a contributory cause of psychosis?

Objective: To assess whether cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychosis in that it may precipitate psychosis in vulnerable individuals. Method: We reviewed longitudinal studies of adolescents and young adults that examined the relations between self-reported cannabis use and the risk of diagnosis with a psychosis or of reporting psychotic symptoms. We also reviewed studies that controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. We assessed evidence for the biological plausibility of a contributory causal relation. Results: Evidence from 6 longitudinal studies in 5 countries shows that regular cannabis use predicts an increased risk of a schizophrenia diagnosis or of reporting symptoms of psychosis. These relations persisted after controlling for confounding variables, such as personal characteristics and other drug use. The relation did not seem to be a result of cannabis use to self-medicate symptoms of psychosis. A contributory causal relation is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter systems with which the cannabinoid system interacts, as demonstrated by animal studies and one human provocation study. Conclusion: It is most plausible that cannabis use precipitates schizophrenia in individuals who are vulnerable because of a personal or family history of schizophrenia.

Young children, adolescents and alcohol - Part I: Exploring knowledge and awareness of alcohol and related issues

This article explores young children's and adolescents' views pertaining to: knowledge and awareness of alcohol and alcohol related issues; social situations in which. alcohol use is present; orientation to alcohol risk; perceived and actual alcohol use; social image and reputation; and short and long term health beliefs in relation to alcohol. Forty focus groups were conducted with 240 primary school students (118 males and 122 females) and 24 focus groups were conducted with 192 high school students (90 males and 102 females); the total being 64 focus groups comprising 432 school students. Participants ages ranged from five years three months to 16 years 10 months. The videotaped discussions revealed that approximately 75% of the primary school-aged children and almost all of the high school students reported that they had tasted alcohol. Parents were primarily responsible for providing the alcohol. Virtually all participants recognised and were able to correctly name a selection of alcoholic and non-alcoholic beverages, and levels of knowledge and awareness of the health and safety aspects of alcohol were relatively mixed. Presentation of bottles and cans was reported as being important in attracting young persons. These data suggest there is an urgent need for research addressed to the development of prevention/intervention education curriculum materials for use with primary school-aged children.