Psychosis Studies

Laboratory Head

Prof Christos Pantelis

Members

Naveen Thomas (Research Psychiatrist)

Mahesh Jayaram (Research Psychiatrist)

Antonia Merritt (Research Coordinator)

Parsa Ravanfar (PhD Candidate)

Ali Stevens (Research Assistant)

Dr Sandra Luza (Research Fellow)

Ulysse Thivisol (PhD Candidate)

Yoshito Saito (PhD Candidate)

Our goal is to understand the neurobiological basis of disorders emerging in childhood and adolescence, including psychotic disorders. Our studies investigate these disorders longitudinally, within the context of brain maturation. We seek to understand the pattern and timing of changes as these disorders emerge and become established; and to identify neurobiological, neuropsychological and genetic markers of these illnesses. This will improve early (pre-illness) detection and diagnosis, and provide novel mechanisms for treatment.

Translating Membrane Proteins Into Therapeutics: From Bedside To Bench

This Program will build on previous pioneering work in order to address the following:

1. Improving understanding of how drugs interact with G-Protein Coupling Receptors (GPCRs) to achieve diverse pharmacology.

2. Improving understanding of the link between receptor and cellular behaviour, signaling and disease efficacy.

3. Increasing understanding of drivers of disease, to better treat specific symptom domains and increase understanding of the interplay of disease context on drug responses.

This Program of work will run for 5 years, with the MNC leading multiple projects relating to translational biology. Specifically, the Program aims to map brain-structure-function relationships and molecular signatures across developmental stages, the impact of insults at each of the stages, and the appropriate choice of pharmacological intervention to ameliorate their impact.

Funding: NHMRC Program Grant

Treatment Resistant Schizophrenia Biobank

The TRS Biobank (formerly known as the CRC for Mental Health) was established in 2011 under the Australian Government’s Cooperative Research Centre (CRC) programme. Its overall purpose was to utilise Australia’s world-leading researcher base to discover, validate and commercialise biomarkers and therapeutics for the treatment of neurodegenerative disease, psychoses and mood disorders.

The TRS Biobank cohort consists of three groups: volunteers who had a diagnosis schizophrenia and were being treated with clozapine at the time of their assessment; first degree relatives (mostly unaffected siblings) of these volunteers; and unrelated individuals who do not have schizophrenia. Blood, RNA and DNA samples, neuroimaging data and other clinical assessment information have been collected and are maintained by TRS Biobank researchers for use in the identification of biomarkers to assist in developing targeted treatments.

Funding: Australian Government's CRC programme

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Microglial Study

The Microglial study aimed to investigate neurobiological processes associated with progressive brain changes that are observed in schizophrenia. Specifically, it investigated whether microglial activity, a marker of neuroinflammation, is elevated in a subgroup of schizophrenia and related to progressive brain changes and clinical disability. The activation of microglia can be detected and quantified using positron emission tomography (PET) and tracers that bind to a receptor in the brain called TSPO. This study involved PET imaging and longitudinal assessment of brain structure and function, clinical, cognitive and blood assessment over a 12-month period. The study completed in 2018 although analyses of the data are still taking place.

Funding: NHMRC, Brain and Behaviour Research Foundation, The University of Melbourne

Personalised Prognostic Tools For Early Psychosis Management - Translating Research Into Clinical Practice (PROSCAN)

PROSCAN has been developed to contribute data to two large European Union (EU) Consortia – PSYSCAN and PRONIA. Both consortia have been separately assembled to address questions regarding prognosis and management of early stages of psychotic illness. There is substantial overlap in the measures and assessment schedules for the PSYSCAN and PRONIA consortia. PROSCAN was developed to harmonise the PSYSCAN and PRONIA protocols into a single study in Melbourne that will contribute data to both consortia. PROSCAN will subsequently aid the EU Consortia in the development and validation of clinical tools to be used to predict course and outcome, analysis of treatment response and monitoring of disease progression in individuals at ultra-high risk (UHR) of psychosis and individuals with first episode psychosis (FEP).

Funding: NHMRC Project Grant

Collaborator: Orygen, The National Centre of Excellence in Youth Mental Health

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Key Publications

Frontal-striatal cognitive deficits in patients with chronic schizophrenia. (1997) C Pantelis, TR Barnes, HE Nelson, S Tanner, L Weatherley, AM Owen, ... Brain, 120 (10), 1823-1843.

Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison, C Pantelis, D Velakoulis, ... McGuire, P. (2003) Lancet, 361 (9354), 281-288.

Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia. (2005) C Pantelis, M Yücel, SJ Wood, D Velakoulis, ... Schizophr bull, 31 (3), 672-696.

Hippocampal and amygdala volumes according to psychosis stage and diagnosis: A magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra–high-risk individuals. (2006) D Velakoulis, SJ Wood, MTH Wong, PD McGorry, ... C Pantelis Arch gen psychiatry 63 (2), 139-149.

Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. (2009) T Takahashi, SJ Wood, AR Yung, B Soulsby, PD McGorry, M Suzuki, ... C Pantelis. Archives of general psychiatry 66 (4), 366-376.

Delayed development of brain connectivity in adolescents with schizophrenia and their unaffected siblings. (2015) A Zalesky, C Pantelis, ..., JL Rapoport, N Gogtay. JAMA psychiatry, 72 (9), 900-908.

Accelerated gray and white matter deterioration with age in schizophrenia. (2016) VL Cropley, ..., C Pantelis*, A Zalesky*, Am J Psychiatry, 174 (3), 286-295.

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia. (2017) MA Di Biase, A Zalesky, ..., C. Pantelis*, V Cropley*, Transl psychiatry, 7 (8), e1225.

Role of positive parenting in the association between neighborhood social disadvantage and brain development across adolescence. (2017) S Whittle, .., C Pantelis, .., JAMA psychiatry, 74 (8), 824-832.

Fragility and volatility of structural hubs in the human connectome. (2018) LL Gollo, JA Roberts, VL Cropley, MA Di Biase, C Pantelis, A Zalesky, M Breakspear. Nature neuroscience 21 (8), 1107.