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Professor John McGrath - Epidemiology and Developmental Neurobiology
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John McGrath received his medical degree from the University of Queensland. After working as a community-based psychiatrist, he moved into full-time research, becoming the Director of the Queensland Centre for Mental Health Research in 1990. He holds appointments at the University of Queensland Department of Psychiatry, the Queensland Brain Institute and Griffith University.
His research aims to generate and evaluate nongenetic risk factors for schizophrenia. He has forged productive cross-disciplinary collaborations linking risk factor epidemiology with developmental neurobiology (e.g. using animal models to explore candidate exposures). In addition, he has supervised major systematic reviews of the incidence, prevalence and mortality of schizophrenia. He has won several national and international awards including the Premier's Award for Medical Research, a Queensland-Smithsonian Fellowship, a Rockefeller Foundation Bellagio Residency, and the Organon Senior Research Award. The Australian government awarded John a Centenary Medal in 2003 and in 2007 he was appointed a Member of the Order of Australia (AM). He is on the editorial boards of several international journals, and has published over 200 peer-reviewed articles and book chapters.
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Schizophrenia is thought to be a developmental disorder with a characteristic onset in late adolescence and early adulthood. Neurodevelopmental theories suggest that genetic and nongenetic factors that disrupt early brain development contribute the risk of developing Schizophrenia. This makes the study of developmental neurobiology important for schizophrenia research. Our research team develops animal models that are (a) informed by epidemiology, and (b) cross-links with key neurobiological correlates of schizophrenia. We focus our research on epidemiologically-informed risk factors for schizophrenia that have obvious public health implications.
Projects
Developmental vitamin D deficiency and risk of schizophrenia
In light of the appreciable effect size, consistency and population-attributable fractions associated with environmentally-mediated risk factors (e.g. migrant status, urbanicity, season of birth), the research community needs to actively generate novel environmental risk factors that may influence the risk of schizophrenia, and assertively pursue research programs that explore these candidates
Our group has discovered that vitamin D influences brain development. Over the last decade, we have undertaken a co-ordinated a program of integrated epidemiology and developmental neuroscience. In collaboration with researchers from Denmark, we have shown that neonatal vitamin D status is associated with risk of schizophrenia. Based on rodent models, we are exploring neurobiological mechanisms of how low vitamin D during early life may result in an increased risk of neurodevelopmental disorders such as schizophrenia. This work is a practical demonstration of how coordinated research programs can translate clues from epidemiology into neuroscience discovery.
Advanced paternal age and risk of schizophrenia
There is robust epidemiological evidence indicating that the offspring of older fathers have an increased risk of autism and schizophrenia. The mechanisms underlying this association remain unclear. Because the male germ line (the precursor of sperm) undergoes many more cell division across adulthood in contrast to the female germ line (the precursor of the oocyte), the increased load of copy error mutations in the sperm of older fathers may underlie the link between paternal age and risk of neurodevelopmental disorders. Changes in epigenetic factors in the sperm of older fathers may also influence subsquent brain development in the offspring. By using mouse models of advanced paternal age, we hope to elucidate mechanisms underpinning disorders such as autism and schizophrenia. Because age of parenthood is being delayed in many nations, understanding the impact of advanced paternal age on offspring health could have important future public health implications.
http://www.researcherid.com/rid/G-5493-2010
R Vieth, H Bischoff-Ferrari, BJ Boucher, B Dawson-Hughes, CF Garland, RP Heaney, MF Holick, BW Hollis, C Lamberg-Allardt, JJ McGrath, AW Norman, R Scragg, SJ Whiting, WC Willett, and A Zittermann. (2007) The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr ; 85: 649.
Jablensky A, McGrath J, Herrman H, Castle D, Gureje O, Carr V, Morgan V, Korten A. Harvey C (2000). Psychotic disorders in urban areas. Australian and New Zealand Journal of Psychiatry. 34: 221-236.
Saha S, Welham J, Chant D, McGrath JJ. (2005) A systematic review of the prevalence of schizophrenia. PLOS Medicine;2(5):e141.
S Saha, D Chant, J McGrath. (2007) A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Archives of General Psychiatry 64(10); 1123-31.
McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. (2004) A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Medicine. 2004 Apr 28;2(1):13.
Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. (2005) Distribution of the vitamin D receptor and 1-hydroxylase in human brain. J Chem Neuroanat: 29(1):21-30.
McGrath J, Welham J, Scott J, Varghese D, Degenhardt L, Hayatbakhsh M, Alati R, Williams G, Bor W, .Najman J. (2010) Sibling-pair analysis confirms an association between cannabis use and psychosis-related outcomes in a cohort of young adults. Archives of General Psychiatry 67(5):440-7.
Burne T, Scott E, van Swinderen B, Hilliard M, Reinhard J, Claudianos C, Eyles D, McGrath J. (2011) Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish? Molecular Psychiatry 16 (1), 7-16.
Scott J, Welham J, Martin G, Bor W, Najman J, O’Callaghan M, Williams G, Aird R, McGrath J. (2009) Psychopathology during childhood and adolescence predicts delusional-like experiences in adults: a 21 year birth cohort study. American Journal of Psychiatry 166(5):567-74
Eyles D, Anderson C, Ko P, Jones A, Thomas A, Burne T, Mortensen PB, Nørgaard Pedersen B, Hougaard DM, McGrath J. (2009) A sensitive LC/MS/MS assay of 25OH vitamin D3 and 25OH vitamin D2 in dried blood spots. Clin Chim Acta. 403(1-2):145-51.
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