TRANSLATIONAL NEUROBIOLOGY GROUP

The Translational Neurobiology group within the Psychosis Studies research stream investigates relationships between the brain, biology and behaviour in schizophrenia and psychotic disorders in order to understand why and how these disorders develop. We use brain imaging (structural, molecular and functional), cognitive assessment and clinically accessible tissue (blood and cerebrospinal fluid) to investigate the biological mechanisms and brain changes underlying psychotic disorders and their cognitive, clinical and functional correlates. An important aspect of our research is to test and validate models developed at the benchside (e.g. in animal studies) in people living with psychotic disorders across a broad spectrum of disease risk, including subclinical psychosis, help-seeking youth, and during early and established stages of the illness.

MEMBERS:

Eleni Ganella (Research Fellow)

Cassandra Wannan (PhD Candidate)

Dr Ye Tian (RA)

Rebecca Cooper (Honours)

Lilianna Laskaris (PhD Candidate)

Kavisha Fernando (Honours)

Jeffery Weng (Honours)

COMPLEMENT AND CORTICAL THINNING (CCT) STUDY

Psychosis is a severe mental illness that typically emerges in adolescence and young adulthood; a time when substantial brain development is taking place. Recently, elements of the complement cascade have been associated with increased risk of schizophrenia. The complement cascade is involved in innate immunity, and has been shown to be involved in synaptic pruning, a maturational process thought to underlie cortical thinning (grey matter loss) in schizophrenia. However, evidence of this process in living humans is scant. Preliminary data from our group has revealed that elevated complement protein levels in blood, and accelerated loss of grey matter, in the early stages of psychotic illness are related to poor outcome. This project seeks to unify and advance these separate observations to test an integrated model of complement-mediated cortical thinning in the development of psychosis.

The CCT project will i) test whether complement proteins in blood and cerebrospinal fluid are altered in recent-onset schizophrenia, and ii) test whether dysregulation of these proteins are associated with cortical thinning and clinical outcome using a longitudinal design. The project is anticipated to commence by the end of 2019.  

Funding: NHMRC

KEY PUBLICATIONS

Cropley, V.L., Klauser, P., Lenroot, R.K., Bruggemann, J., Sundram, S., Bousman, C., Pereira, A., Di Biase, M.A., Weickert, T.W., Weickert, C.S., Pantelis, C., Zalesky, A., 2017. Accelerated Gray and White Matter Deterioration With Age in Schizophrenia. Am J Psychiatry 174(3), 286-295.

 

Di Biase, M.A., Zalesky, A., O'Keefe, G., Laskaris, L., Baune, B.T., Weickert, C.S., Olver, J., McGorry, P.D., Amminger, G.P., Nelson, B., Scott, A.M., Hickie, I., Banati, R., Turkheimer, F., Yaqub, M., Everall, I.P., Pantelis, C., Cropley, V., 2017. PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia. Transl Psychiatry 7(8), e1225.

 

Laskaris, L., Zalesky, A., Weickert, C.S., Di Biase, M.A., Chana, G., Baune, B.T., Bousman, C., Nelson, B., McGorry, P., Everall, I., Pantelis, C., Cropley, V., 2018. Investigation of peripheral complement factors across stages of psychosis. Schizophr Res.

 

Laskaris, L.E., Di Biase, M.A., Everall, I., Chana, G., Christopoulos, A., Skafidas, E., Cropley, V.L., Pantelis, C., 2016. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol 173(4), 666-680.

 

Wannan, C.M.J., Cropley, V.L., Chakravarty, M.M., Van Rheenen, T.E., Mancuso, S., Bousman, C., Everall, I., McGorry, P.D., Pantelis, C., Bartholomeusz, C.F., 2018. Hippocampal subfields and visuospatial associative memory across stages of schizophrenia-spectrum disorder. Psychol Med, 1-11.

 

Cropley, V.L., Lin, A., Nelson, B., Reniers, R., Yung, A.R., Bartholomeusz, C.F., Klauser, P., Velakoulis, D., McGorry, P., Wood, S.J., Pantelis, C., 2016. Baseline grey matter volume of non-transitioned "ultra high risk" for psychosis individuals with and without attenuated psychotic symptoms at long-term follow-up. Schizophr Res 173(3), 152-158.

 

Cropley, V.L., Fujita, M., Innis, R.B., Nathan, P.J., 2006. Molecular imaging of the dopaminergic system and its association with human cognitive function. Biol Psychiatry 59(10), 898-907.

Melbourne

Neuropsychiatry

Centre

University of Melbourne and

Melbourne Health

Melbourne Neuropsychiatry Centre

Level 3, Alan Gilbert Building

161 Barry Street

Carlton, Victoria, 3053

AUSTRALIA