Prof Peter Schofield

TEAM LEADER PROFILE

Executive Director and Chief Executive Officer, NeuRA Professor, School of Medicine, UNSW

+612 9399 1604


Appointed institute head in 2004, Peter graduated from the University of Sydney with the University Medal and was awarded a PhD in genetics from The Australian National University in 1985. He undertook postdoctoral positions in biotechnology in the US and the University of Heidelberg. Peter was appointed a NHMRC Senior Research Fellow at the Garvan Institute in 1993, becoming head of the Neurobiology Research Program in 1999. His research interests focus on identifying genes that lead to mental illness and to dementia.

Projects Prof Peter Schofield is currently involved with

CURRENT PROJECTS

Genetic and epigenetic contributors to bipolar disorder in a high risk cohort

The offspring of individuals with bipolar disorder are at increased risk of mental illness, but our tools to predict which of these genetically at-risk young people will eventually develop disorder are very imprecise. Longitudinal studies that ascertain at-risk participants and monitor them prospectively are an effective approach for identifying early clinical and biological markers of future illness. In collaboration with the Black Dog Institute plus groups from four independent US-based sites, including: Johns Hopkins University; University of Michigan; Washington University in St. Louis; Indiana University; we are following a cohort of young kids and siblings of bipolar disorder patients with annual clinical, neurocognitive and lifestyle assessments; plus bi-annual brain imaging of the Australian participants. We are assessing the genetic load of multiple risk variants across the genome in these at-risk individuals to determine if we can use genetic information to help predict which individuals will ultimately transition to illness, and whether genetic load will influence early structural brain changes which are seen prior to onset of symptoms which lead to a clinical diagnosis.

We are also examining whether epigenetic changes – which occur on-top-of the DNA sequence in response to environmental influences – are involved in transition from health to illness. Early identification of those most likely to develop illness will provide a firm basis on which to develop preventive and early intervention strategies to reduce the impact of this devastating disorder.

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Genetic and epigenetic contributors to bipolar disorder in a high risk cohort

International collaborative consortia involvement

In addition to genes identified in our own laboratory, we have also been involved in assessing the risk attributed by genes identified by other groups and in sharing data and samples in large international collaborative studies. We are contributors to the Psychiatric Genomics Consortium (PGC) and Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortia, which aim to identify risk genes which contribute to disease, and examine their effect on brain structure, function and disease.

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International collaborative consortia involvement

Investigation of rare variants which increase risk to bipolar disorder

Recent advances in technology have enabled sequencing at the level of the entire genome to become a reality. We have access to number of rare families with highly heritable forms of bipolar disorder, for which we will apply this powerful technology to identify specific genetic factors which increase disease risk. We will assess loss-of-function variation within genes, at both the level of single base mutations and variation in gene copy number, which track with illness in these families to identify new genes which contribute to illness.

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Investigation of rare variants which increase risk to bipolar disorder

Genetic contributors, clinical course and pharmacogenomics of Bipolar Disorder

Bipolar Disorder is a severe and debilitating psychiatric condition, for which the clinical course is highly variable between individuals, and the specific genetic causes remain largely obscure. This landmark study aims to use state-of-the-art whole genome sequencing technology to address four key knowledge gaps:

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Genetic contributors, clinical course and pharmacogenomics of Bipolar Disorder

Quantitative trait analysis of bipolar disorder

Genetic research into bipolar disorder traditionally uses strict categorical criteria to define a clinical diagnosis. However, it is common for relatives of individuals with bipolar to exhibit some evidence of mood disturbance, but not sufficient to meet the strict clinical criteria for a positive diagnosis. These individuals are correctly considered clinically unaffected, although they likely share some of the susceptibility genes underlying the disorder. Dr Fullerton has been examining the use of subclinical traits to identify individuals who share susceptibility genes in order to follow the pattern of genetic transmission of bipolar disorder through families more accurately.

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Quantitative trait analysis of bipolar disorder

Epigenetic and childhood trauma in psychotic and mood disorder

This project examines epigenetic (methylation) markers of childhood trauma in schizophrenia and bipolar disorder patients.

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Epigenetics and childhood trauma

Genetics and neuroscience of resilience and wellbeing

Mental health and wellbeing is not simply the absence of mental illness, yet we know very little about its underlying mechanisms in relative comparison. Dr Justine Gatt and Prof Peter Schofield, together with Prof Leanne Williams (Stanford University) are studying the genetics and neuroscience of resilience and wellbeing in a prospective cohort of 1,600 healthy adult twins. They have recently developed a new 26-item composite scale of wellbeing called COMPAS-W (Gatt et al., 2014, Psychiatry Res), with genetic modelling demonstrating a heritability estimate of 48% for total wellbeing. Multivariate modelling further suggested common genetic factors contributed to wellbeing and its subcomponents of composure, own-worth, mastery, positivity, achievement and satisfaction. Now they are aiming to understand the neuroscience of wellbeing and resilience, how different genes and environments modulate pathways to mental health, and how e-health tools can promote resilience against life stressors.

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Genetics and neuroscience of resilience and wellbeing

Investigation of genetic interactions which increase risk to bipolar disorder

Because of the complex pattern of genetic transmission, it is expected that multiple genes will contribute to susceptibility to bipolar disorder. It is possible that combinations of genes will be stronger risk factors for developing bipolar disorder than individual genes, so we are examining gene-gene interactions (genetic epistasis) throughout the genome to identify genes which, in concert, may increase susceptibility. This analysis has led to the identification of multiple such interacting regions, and the group is now seeking to identify the specific genes involved in these interactions.

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Investigation of genetic interactions which increase risk to bipolar disorder

Identification and characterisation of ST8SIA2: a generalised mental illness susceptibility gene

Together with Professor Peter Schofield (NeuRA) and Professor Philip Mitchell (Black Dog Institute), our group is investigating the genetic contributors to bipolar disorder using Australian families with multiple individuals who have been diagnosed with the disorder.

The group previously identified a bipolar susceptibility locus located on chromosome 15 in a pooled analysis of 35 families. More detailed analysis of this region has identified a single gene, which confers an increased susceptibility to both bipolar disorder and schizophrenia, and has also been implicated as a risk factor for autism.

The group is now aiming to understand how alterations in ST8SIA2 translate into an increased genetic susceptibility by characterising alterations in the DNA, RNA and protein product of this gene and its interaction partners in patients with either bipolar disorder or schizophrenia.

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Identification and characterisation of ST8SIA2: a generalised mental illness susceptibility gene

Genetics of early onset Alzheimer’s disease

Dementia is usually thought of as a disease of ageing. However, the burden of young onset dementia, with symptoms occurring before age 65, has recently been identified as an important area not well supported by the health care system. Dr Bill Brooks has continued his development of information and support systems for use by families that have early onset hereditary dementias.

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Genetics of early onset Alzheimer’s disease

Genetics of bipolar disorder

Both genetic and environmental factors are involved in the development of bipolar disorder, a severe mood disorder characterised by oscillations from normal mood to periods of elevated mood (mania) or low mood (depression). Dr Jan Fullerton and Professor Peter Schofield are investigating the genetic contributors to bipolar disorder using Australian families with multiple individuals who have been diagnosed with the disorder. Together with PhD student Erica McAuley, the group has recently identified a bipolar susceptibility locus located on chromosome 15 in a pooled analysis of 35 families. Further, more detailed analysis of this region using a newly acquired campus Illumina beadstation facility for the analysis of SNP markers has identified a single gene, which confers an increased susceptibility to bipolar disorder. They are now aiming to understand how these alterations translate into an increased genetic susceptibility by characterising the biological pathways involved.

Because of the complex pattern of genetic transmission, they expect that multiple genes will contribute to susceptibility to bipolar disorder. It is possible that combinations of genes will be stronger risk factors for developing bipolar disorder than individual genes, so they are examining gene-gene interactions (genetic epistasis) throughout the genome to identify genes which, in concert, may increase susceptibility. This analysis has led to the identification of multiple such interacting regions, and they are now seeking to identify the specific genes involved in these interactions.

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Genetics of bipolar disorder

Genes, environment and depression

In a collaborative study with Professors Kay Wilhelm and Phil Mitchell from the UNSW School of Psychiatry, Professor Peter Schofield and his team examined the genetic variation in the transporter protein that is involved in the reuptake of the neurotransmitter serotonin. There is an association between low serotonin transporter levels, stress and depression. The group has further shown that there is an association between the serotonin transporter genotypes and the way an individual copes with stress. This has led to further clinical studies correlating how individuals can use different methods to handle stress. Their research has significant implications for reducing the likelihood of developing depression and a planned future study will be to evaluate whether specific training in stress management, matched to an individual’s genotype, may lead to a reduction in the incidence of depression.

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Genes, environment and depression

Genetics of normal brain function and links to anxiety and depression symptoms

Using various cognitive, psychological and neuroimaging measures, they have investigated the role of several genes known to be involved in brain disorders.

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Genetics of normal brain function and links to anxiety and depression symptoms

The TWIN-E study in emotion and cognition

The overall goal of this project is to establish the role of genetics versus environment for each measure of emotion and cognition, as well as resting state function, using twin modelling.

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The TWIN-E study in emotion and cognition

RESEARCH TEAM

Kerrie Pierce

KERRIE PIERCE Senior Research Assistant

ANNA HEATH Research Assistant

Mirelle D'Mello

MIRELLE D’MELLO Research Assistant