Melbourne School of Population and Global Health - Research Publications
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ItemSometimes It's Good to be Short: The Serotonin Transporter Gene, Positive Parenting, and Adolescent Depression(WILEY, 2019-07)In threatening environments, the short (S) allele of 5-HTTLPR is proposed to augment risk for depression. However, it is unknown whether 5-HTTLPR variation increases risk for depression in environments of deprivation, lacking positive or nurturant features. Two independent longitudinal studies (n = 681 and 176, respectively) examined whether 5-HTTLPR moderated associations between low levels of positive parenting at 11-13 years and subsequent depression at 17-19 years. In both studies only LL homozygous adolescents were at greater risk for depression with decreasing levels of positive parenting. Thus, while the S allele has previously been identified as a susceptible genotype, these findings suggest that the L allele may also confer sensitivity to depression in the face of specific environmental challenges.
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ItemCounting up the risks: How common are risk factors for morbidity and mortality in young people with psychosis?(WILEY, 2018-12)BACKGROUND: This study examined the prevalence of risk factors for cardiovascular (CV)-related morbidity and mortality in young people with psychosis aged 18 to 24 years. METHODS: The study included 132 people aged 18 to 24 years who participated in the 2010 second Australian national survey of people living with psychosis. The 2009 World Health Organisation (WHO) Global Health Risks report was used as a framework to determine which specific risk factors were present in each in these young people. The risk factors assessed in this study were smoking, alcohol use, hypertension, overweight/obesity, physical inactivity, high blood glucose, high cholesterol and poor diet. Each risk factor was defined according to WHO criteria. A count of the total number of risk factors present for each participant was determined. Data for male and female participants were compared. RESULTS: Young men had an average of 2.9 (SD 1.2) risk factors. Young women had an average of 2.4 (SD 1.2) risk factors. The most common risk factors were low fruit and vegetable intake (77.9%), cigarette smoking (67.7%), overweight/obesity (55%) and physical inactivity (39.8%). There were no significant differences between men and women in the number of risk factors present, or the prevalence of individual risk factors. CONCLUSION: This study demonstrated that many of the risk factors that ultimately contribute to disability and premature death are present at an early age in people with psychosis. Preventive measures need to be an integral component of early intervention services for this client population to avert progression to serious CV morbidity and early mortality.
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ItemEffects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis(NATURE PUBLISHING GROUP, 2013-04)Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37-4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05-2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of 3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.
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ItemCardiometabolic Risk Indicators That Distinguish Adults with Psychosis from the General Population, by Age and Gender(PUBLIC LIBRARY SCIENCE, 2013-12-18)Individuals with psychosis are more likely than the general community to develop obesity and to die prematurely from heart disease. Interventions to improve cardiovascular outcomes are best targeted at the earliest indicators of risk, at the age they first emerge. We investigated which cardiometabolic risk indicators distinguished those with psychosis from the general population, by age by gender, and whether obesity explained the pattern of observed differences. Data was analyzed from an epidemiologically representative sample of 1,642 Australians with psychosis aged 18-64 years and a national comparator sample of 8,866 controls aged 25-64 years from the general population. Cubic b-splines were used to compare cross sectional age trends by gender for mean waist circumference, body mass index [BMI], blood pressure, fasting blood glucose, triglycerides, LDL, HDL, and total cholesterol in our psychosis and control samples. At age 25 individuals with psychosis had a significantly higher mean BMI, waist circumference, triglycerides, glucose [women only], and diastolic blood pressure and significantly lower HDL-cholesterol than controls. With the exception of triglycerides at age 60+ in men, and glucose in women at various ages, these differences were present at every age. Differences in BMI and waist circumference between samples, although dramatic, could not explain all differences in diastolic blood pressure, HDL-cholesterol or triglycerides but did explain differences in glucose. Psychosis has the hallmarks of insulin resistance by at least age 25. The entire syndrome, not just weight, should be a focus of intervention to reduce mortality from cardiovascular disease.
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ItemRisk Factors for Obstructive Sleep Apnea Are Prevalent in People with Psychosis and Correlate with Impaired Social Functioning and Poor Physical Health(FRONTIERS MEDIA SA, 2016-08-31)BACKGROUND: Obstructive sleep apnea (OSA) in the general community is associated with obesity, smoking, alcohol, and sedative medication use and contributes to depressed mood, daytime sedation, and sudden cardiovascular deaths. Poor cardiovascular health, impaired social functioning, and negative and cognitive symptoms are also among the common clinical features of psychotic disorders. People with psychosis have higher rates of sleep disturbance; however, OSA has not been extensively investigated in this population. AIMS: This study aimed to determine the prevalence of OSA and general sleep disruption symptoms in a representative Australian sample of people with psychosis. We investigated the prevalence of potential risk factors for OSA, including obesity, psychotropic medications, and substance abuse in this population. Finally, we evaluated associations between symptoms of OSA, symptoms of general sleep disruption, and various clinical features in people with psychosis. METHODS: Participants took part in the Second National Australian Survey of Psychosis, a population-based survey of Australians with a psychotic disorder aged 18-64 years. Symptoms associated with OSA (snoring and breathing pauses during sleep) in the past year were assessed using questions from the University of Maryland Medical Centre Questionnaire and symptoms associated with general sleep disruption in the past week using the Assessment of Quality of Life Questionnaire. Data collected included psychiatric diagnosis and symptoms, education, employment, medications, smoking status, physical activity, drug and alcohol use, and cognitive function. Physical health measures included body mass index, waist circumference, blood pressure, fasting blood glucose, and lipids. RESULTS: Snoring was reported by 41.9%; 7% stating they frequently stopped breathing (pauses) during sleep. Univariate logistic regressions show OSA symptoms (pauses and snoring) were associated with older age, female gender, lower levels of social participation or employment, cardiovascular risk factors, sedentary lifestyle, and poorer quality of life, while symptoms of general sleep disruption were more likely in people with depressive symptoms. CONCLUSION: Australians with psychosis have high levels of sleep disturbance, including OSA. OSA symptoms were associated with cardiovascular disease risk factors, reduced social participation and employment, and poorer quality of life. Whether correction of OSA can improve these factors in people with psychosis remains to be determined.
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ItemPredictors of functional status at service entry and discharge among young people with first episode psychosis(SPRINGER HEIDELBERG, 2017-05)OBJECTIVE: Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. METHOD: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). RESULTS: 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. CONCLUSIONS: Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.
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ItemAssociation between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study(SPRINGERNATURE, 2014-09)The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13-19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.
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ItemLinking the Serotonin Transporter Gene, Family Environments, Hippocampal Volume and Depression Onset: A Prospective Imaging Gene X Environment Analysis(AMER PSYCHOLOGICAL ASSOC, 2015-11)A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume.
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ItemAustralian Twin Registry: 30 Years of Progress(CAMBRIDGE UNIV PRESS, 2013-02)The Australian Twin Registry (ATR) is a national volunteer resource of twin pairs and higher-order multiples willing to consider participating in health, medical, and scientific research. The vision of the ATR is 'to realize the full potential of research involving twins to improve the health and well-being of all Australians'. The ATR has been funded continuously by the National Health and Medical Council for more than 30 years. Its core functions entail the recruitment and retention of twin members, the maintenance of an up-to-date database containing members' contact details and baseline information, and the promotion and provision of open access to researchers from all institutes in Australia, and their collaborators, in a fair and equitable manner. The ATR is administered by The University of Melbourne, which acts as custodian. Since the late 1970s the ATR has enrolled more than 40,000 twin pairs of all zygosities and facilitated more than 500 studies that have produced at least 700 peer-reviewed publications from classical twin studies, co-twin control studies, within-pair comparisons, twin family studies, longitudinal twin studies, randomized controlled trials, and epigenetics studies, as well as studies of issues specific to twins. New initiatives include: a Health and Life Style Questionnaire; data collection, management, and archiving using a secure online software program (The Ark); and the International Network of Twin Registries. The ATR's expertise and 30 years of experience in providing services to national and international twin studies has made it an important resource for research across a broad range of disciplines.