Melbourne Medical School Collected Works - Research Publications
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ItemFamily risk factors for cannabis use: a population-based survey of Australian secondary school students(CARFAX PUBLISHING, 2003-06-01)The objective of this study was to investigate relationships between adolescent cannabis use and indices of parent - child attachment, family functioning and parent attitudes to drugs and delinquency. A total of 2848 year 9 and 2363 year 11 students participated in the Victorian Adolescent Health and Well-Being Survey (1999). The study was a school-based random sample of 535 metropolitan and rural, government and non-government secondary schools throughout Victoria, Australia. Cannabis use was defined as 'any' and 'weekly' use in the last 30 days. Multivariate logistic regression was used to identify independent associations between cannabis use and parent - child attachment, family functioning and parent attitudes to drugs and delinquency. Cannabis use in year 9 was associated with permissive parent attitudes to drugs and delinquency (any use: adjusted odds ratio (OR) = 8.1; weekly use: adjusted OR = 7.6), and was particularly sensitive to small changes in the quality of the parent - child relationship with risk increasing threefold for those describing their attachment as 'good' compared with 'very good' (any use: adjusted OR = 2.8, weekly use adjusted OR = 2.9). A similar, but more moderate pattern association was evident in year 11. After adjusting for other family and background factors, poor family functioning showed minimal association with level of cannabis use at both year levels. Results suggest that intervention efforts might sensibly target strengthening parent - children relationships and promoting less permissive parent attitudes to drug use.
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ItemNicotine dependence in a prospective population-based study of adolescents: the protective role of a functional tyrosine hydroxylase polymorphism(LIPPINCOTT WILLIAMS & WILKINS, 2004-02-01)Dopamine is a key neurotransmitter of the mesolimbic reward pathway in the human brain, and tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. Consequently, the gene encoding TH is a strong candidate for involvement in the genetic component of addiction. The importance of this gene in nicotine dependence is supported by many studies showing a link between nicotine administration and TH expression. A functional tetranucleotide repeat polymorphism within intron 1 of the TH gene (HUMTH01-VNTR) has been shown to modify tobacco use in two independent Caucasian samples from the USA and Australia. Using information drawn from an eight-wave Australian population-based longitudinal study of adolescent health, we tested the effect of the HUMTH01-VNTR on nicotine dependence. Comparisons were made between dependent smokers and non-dependent smokers. These data provide further support for a protective association between the K4 allele and dependent smoking (odds ratio 0.54, 95% confidence interval 0.28-1.0). No associations were observed at any of three other common TH polymorphisms (rs6356, rs6357 and HUMTH01-PstI). Including these data, three independent studies, two of which use identical phenotypes, have now identified a protective relationship between the K4 allele of the functional HUMTH01-VNTR polymorphism and high-level smoking.
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ItemCOMT Val(158)Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study(BLACKWELL PUBLISHING, 2007-10-01)We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val(158)Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose-response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met(158) [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76-0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79-0.99, P = 0.033). There was no evidence for a dose-response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29-0.70, P < 0.001) among carriers homozygous for both the COMT Met(158) and the 5HTTLPR Short alleles (Met(158)Met + Short-Short) compared with the remaining cohort. The double-recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.
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ItemVariation in the gene coding for the M5 Muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction: evidence from a prospective population based cohort study of young adults(BMC, 2007-07-03)BACKGROUND: The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R) is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine. Mice lacking M5R show a substantial reduction in both reward and withdrawal responses to morphine and cocaine. The CHRM5, the gene that codes for the M5R, is a strong biological candidate for a role in human addiction. We screened the coding and core promoter sequences of CHRM5 using denaturing high performance liquid chromatography to identify common polymorphisms. Additional polymorphisms within the coding and core promoter regions that were identified through dbSNP were validated in the test population. We investigated whether these polymorphisms influence substance dependence and dose in a cohort of 1947 young Australians. RESULTS: Analysis was performed on 815 participants of European ancestry who were interviewed at wave 8 of the cohort study and provided DNA. We observed a 26.8% increase in cigarette consumption in carriers of the rs7162140 T-allele, equating to 20.1 cigarettes per week (p=0.01). Carriers of the rs7162140 T-allele were also found to have nearly a 3-fold increased risk of developing cannabis dependence (OR=2.9 (95%CI 1.1-7.4); p=0.03). CONCLUSION: Our data suggest that variation within the CHRM5 locus may play an important role in tobacco and cannabis but not alcohol addiction in European ancestry populations. This is the first study to show an association between CHRM5 and substance use in humans. These data support the further investigation of this gene as a risk factor in substance use and dependence.
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ItemChildhood sexual abuse and eating disorders in females: findings from the Victorian Adolescent Health Cohort Study(American Medical Association, 2008)Objective: To examine the relationship between childhood sexual abuse (CSA) before the age of 16 years and later onset of bulimia and anorexia nervosa symptoms in females. Design: A longitudinal cohort study of adolescents observed from August 1992 to March 2003. The cohort was defined in a 2-stage cluster sample using 44 Australian schools in Victoria. Setting: Population based. Participants: A total of 1936 persons participated at least once and survived to the age of 24 years, including 999 females. The mean (SD) age of females at the start of follow- up was 14.91 (0.39) years; and at completion, 24.03 (0.55) years. Main Exposure: Self-reported CSA before the age of 16 years was ascertained retrospectively at the age of 24 years. Outcome Measures: Incident Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)–defined partial syndromes of anorexia and bulimia nervosa were identified between waves 4 (mean age, 16.3 years) and 6 (mean age, 17.4 years) using the Branched Eating Disorder Test. Results: The incidence of bulimic syndrome during adolescence was 2.5 (95% confidence interval, 0.80-8.0) times higher among those who reported 1 episode of CSA and 4.9 (95% confidence interval, 1.9-12.7) times higher among those who reported 2 or more episodes of CSA, compared with females reporting no episodes, adjusted for age and background factors. The association persisted after adjusting for possible confounders or mediators measured 6 months earlier, including psychiatric morbidity and dieting behavior. There was little evidence of an association between CSA and partial syndromes of incident anorexia nervosa. Conclusion: Childhood sexual abuse seems to be a risk factor for the development of bulimic syndromes, not necessarily mediated by psychiatric morbidity or severe dieting.
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ItemPredicting Female Depression Across Puberty: A Two-Nation Longitudinal Study(ELSEVIER SCIENCE INC, 2008-12-01)OBJECTIVE: To prospectively examine the relation between pubertal stage and the onset and course of depressive symptoms. METHOD: The design was a three-wave longitudinal study of health and social development using statewide community samples in Washington, United States, and Victoria, Australia. Approximately 5,769 students initially ages 10 to 15 years were assessed for depressive symptoms with the Short Mood and Feelings Questionnaire. Pubertal status was assessed using a self-report version of the Pubertal Development Scale. RESULTS: Advancing pubertal stage carried higher risks for depressive symptoms in female subjects in all of the three study waves. The pubertal rise in female depressive symptoms was due to both higher risk for incident cases and an even greater effect on risks for persistence of depressive symptoms. Report of poor emotional control 12 months earlier carried a twofold higher risk for incident depressive symptoms and largely explained the pubertal rise in female incident cases. High family conflict and severity of bullying also predicted persistence of depressive symptoms. Preexisting depressive symptoms were not associated with later increases in the rate of pubertal transition. CONCLUSIONS: Advancing pubertal stage carries risks for both the onset and persistence of depressive symptoms in females. Social adversity around puberty predicts the persistence of symptoms but does not account for a pubertal rise in female depression. A report of poor emotional control may be a useful marker of girls at risk for depressive symptoms and as a target for preventive intervention.