Melbourne Medical School Collected Works - Research Publications

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    Genetics and public health - evolution, or revolution?
    Halliday, JL ; Collins, VR ; Aitken, MA ; Richards, MPM ; Olsson, CA (BMJ PUBLISHING GROUP, 2004-11)
    During the 19th and early 20th century, public health and genetics shared common ground through similar approaches to health promotion in the population. By the mid-20th century there was a division between public health and genetics, with eugenicists estranged and clinical genetics focused on single gene disorders, usually only relevant to small numbers of people. Now through a common interest in the aetiology of complex diseases such as heart disease and cancer, there is a need for people working in public health and genetics to collaborate. This is not a comfortable convergence for many, particularly those in public health. Nine main concerns are reviewed: fear of eugenics; genetic reductionism; predictive power of genes; non-modifiable risk factors; rights of individuals compared with populations; resource allocation; commercial imperative; discrimination; and understanding and education. This paper aims to contribute to the thinking and discussion about an evolutionary, multidisciplinary approach to understanding, preventing, and treating complex diseases.
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    Nicotine dependence in a prospective population-based study of adolescents: the protective role of a functional tyrosine hydroxylase polymorphism
    Anney, RJL ; Olsson, CA ; Lotfi-Miri, M ; Patton, GC ; Williamson, R (LIPPINCOTT WILLIAMS & WILKINS, 2004-02)
    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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    COMT Val158Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence:: results from the Victorian Adolescent Health Cohort Study
    Olsson, CA ; Byrnes, GB ; Anney, RJL ; Collins, V ; Hemphill, SA ; Williamson, R ; Patton, GC (BLACKWELL PUBLISHING, 2007-10)
    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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    Variation 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
    Anney, RJ ; Lotfi-Miri, M ; Olsson, CA ; Reid, SC ; Hemphill, SA ; Patton, GC (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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    Childhood sexual abuse and eating disorders in females: findings from the Victorian Adolescent Health Cohort Study
    Sanci, L ; Coffey, C ; OLSSON, CA ; Reid, S ; Carlin, JB ; Patton, GC (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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    Predicting Female Depression Across Puberty: A Two-Nation Longitudinal Study
    Patton, GC ; Olsson, C ; Bond, L ; Toumbourou, JW ; Carlin, JB ; Hemphill, SA ; Catalano, RF (ELSEVIER SCIENCE INC, 2008-12)
    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.
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    Patterns of adolescent smoking and later nicotine dependence in young adults: A 10-year prospective study
    Van De Ven, MOM ; Greenwood, PA ; Engels, RCME ; Olsson, CA ; Patton, GC (W B SAUNDERS CO LTD, 2010-02)
    OBJECTIVES: There is considerable variability in progression from smoking initiation to established smoking. This paper addresses the extent to which different patterns of adolescent smoking, including periods of cessation, predict smoking status in young adults. STUDY DESIGN: Ten-year, eight-wave prospective cohort study of a state-wide community sample in Victoria, Australia. METHODS: Participants were 1520 students from 44 secondary schools, initially aged 14 to 15 years. Adolescent smoking and quitting patterns were assessed during Waves 1-6 with self-reported frequency of use and a 7-day retrospective diary. The Fagerstrom Test for Nicotine Dependence (ND) was used to assess ND at the age of 24 years (Wave 8). RESULTS: The prevalence of ND in young adults was 16.9% for all adolescent smokers, with prevalence rates of 6.8% and 26.7% for adolescent non-daily and daily adolescent smokers, respectively. Maximum smoking levels, onset of daily smoking, duration of smoking, escalation time and duration of cessation during adolescence predicted later ND. Daily smokers who ceased smoking for at least two waves (> or = 12 months) had a level of risk similar to adolescents who had never smoked. CONCLUSIONS: Quitting smoking as an adolescent substantially alters the risk for later ND. For adolescents who become daily smokers, quitting for 12 months should be the aim in tobacco control and clinical interventions.