Psychosis & Developmental Neuropsychiatry

• 
  Professor
  Christos Pantelis

  cpant@unimelb.edu.au

  View researcher's webpage

Project Details

Research Objective

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 and genetic markers of these illnesses. This will improve early (pre-illness) detection and diagnosis, and provide novel mechanisms for treatment.

Research Focus

Our work focuses on specific psychiatric conditions.

A focus on psychotic disorders
Psychotic disorders, including schizophrenia, first episode psychosis and bipolar disorder, are extremely debilitating and traumatising for the individual and their families. Schizophrenia is characterised by the presence of hallucinations, delusions, bizarre behaviour, flat affect, cognitive impairment and decline in social and occupational functioning. Bipolar disorder is characterised by a disturbance of mood, with periods of elevated or depressed mood, and may be associated with psychotic symptoms.

A focus on individuals 'at risk' of developing psychosis
Psychotic disorders are most likely to develop in adolescence and early adulthood, and may be preceded by 'prodromal' symptoms. Prodromal symptoms typically appear during the teenage years and often include attenuated forms of the full-blown disorder. While the aetiology of psychotic disorders is not clear, a number of contributing factors have been identified, including pre-natal environment, infections, genetics, stress and associated hormones, psychostimulant drugs, and disturbance in neurotransmitter systems, including dopamine. Identifying markers and risk factors of developing psychosis has significant implications for illness prevention.

A focus on childhood disorders
Childhood developmental disorders often present with delayed milestones, poor school performance, language difficulties, and social and behavioural disturbance. We are currently focusing on adolescents who were born preterm, adolescents at risk for depression, as well as studies on children with schizotypal features and autism. Genetic studies are examining whether we can better predict which children will develop autism and related disorders.

Research Framework

Understanding disorders framed within a brain maturational perspective
Our studies focus on a life-long developmental perspective. It is important to consider the clinical observations and research findings for each of these disorders within the context of a person's development and the perspective of brain changes from conception to adulthood.

Why is this important?

• Significant developmental brain changes occur from gestation up until the mid 20s, when the rate of maturation slows down.
• Adolescence is a period of increased vulnerability to the development of many psychiatric illnesses, including schizophrenia and disturbances of mood.
• Our work has identified for the first time that progressive brain changes occur at the earliest stages of psychosis.

We are now seeking to understand how brain changes occur, how they are related to the development of psychiatric disorders, what is their cellular and molecular basis, and how they affect an individual's ability to function. This work is also leading to studies with our neuropathology colleagues, neuroscientists and bioengineers. To achieve these goals we examine brain structure and function in detail using neuropsychological approaches, the latest brain imaging technologies, genetics, and molecular approaches.

Research Methods

• Structural magnetic resonance imaging (MRI)
• Functional MRI (fMRI) to examine brain activity, including resting state brain networks and connectivity
• Positron emission tomography (PET) of microglial activation (and other measures of brain inflammation), and neurotransmitter systems
• Electrophysiological techniques to map brain electrical activity
• Longitudinal MRI techniques to examine illness trajectories and progression
• Genetic (autism and schizophrenia) and cellular techniques (growing neurons from patients)
• Social cognitive interventions
• Treatment studies

Researchers

• Cali Bartholomeusz
• Vanessa Cropley
• Tamsyn Van Rheenen
• Emre Bora
• Rene Testa
• Christina Phassouliotis
• Sarah Whittle
• Stan Skafidas
• Naveen Thomas
• Dominic Dwyer
• Karissa Searle
• Alice Burnett
• Orwa Dandash
• Harvey Jones
• Suzie Lavoie
• Sarah Gale
• Danielle Lowe
• Thomas Whitford

Collaborators

Currently not available

Funding

Currently not available

Research Outcomes

Psychosis

• 1.Pantelis, C., Barnes, T. R., Nelson, H. E., Tanner, S., Weatherley, L., Owen, A. M., & Robbins, T. W. (1997). Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain, 120 ( Pt 10), 1823-1843.
• 2.Pantelis, C., Velakoulis, D., McGorry, P. D., Wood, S. J., Suckling, J., Phillips, L. J., Yung, A. R., Bullmore, E. T., Brewer, W., Soulsby, B., Desmond, P., McGuire, P. K. (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet, 361(9354), 281-288.
• 3.Pantelis, C., Yücel, M., Wood, S. J., Velakoulis, D., Sun, D., Berger, G., Stuart, G. W., Yung, A., Phillips, L., McGorry, P. D. (2005). Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia. Schizophrenia Bulletin, 31(3), 672-696.
• 4.Pantelis, C., Yucel, M., Bora, E., Fornito, A., Testa, R., Brewer, W. J., Velakoulis, D., & Wood, S. J. (2009). Neurobiological Markers of Illness Onset in Psychosis and Schizophrenia: The Search for a Moving Target. Neuropsychol Rev, 19, 385-398.
• 5.Sun, D., Stuart, G. W., Jenkinson, M., Wood, S. J., McGorry, P. D., Velakoulis, D., van Erp, T. G., Thompson, P. M., Toga, A. W., Smith, D. J., Cannon, T. D., & Pantelis, C. (2009). Brain surface contraction mapped in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Mol Psychiatry, 14(10), 976-986.
• 6.Takahashi, T., Wood, S. J., Yung, A. R., Soulsby, B., McGorry, P. D., Suzuki, M., Kawasaki, Y., Phillips, L. J., Velakoulis, D., Pantelis, C. (2009). Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry, 66(4), 366-376.
• 7.Bartholomeusz, C. F., Proffitt, T. M., Savage, G., Simpson, L., Markulev, C., Kerr, M., McConchie, M., McGorry, P. D., Pantelis, C., Berger, G. E., & Wood, S. J. (2011). Relational memory in first episode psychosis: implications for progressive hippocampal dysfunction after illness onset. Aust N Z J Psychiatry, 45(3), 206-213.
• 8.Bora, E., Fornito, A., Radua, J., Walterfang, M., Seal, M., Wood, S. J., Yücel, M., Velakoulis, D., Pantelis, C. (2011). Neuroanatomical abnormalities in schizophrenia: A multimodal voxelwise meta-analysis and meta-regression analysis. Schizophr Res, 127(1-3), 46-57.
• 9.Mechelli, A., Riecher-Rossler, A., Meisenzahl, E. M., Tognin, S., Wood, S. J., Borgwardt, S. J., Koutsouleris, N., Yung, A. R., Stone, J. M., Phillips, L. J., McGorry, P. D., Valli, I., Velakoulis, D., Woolley, J., Pantelis, C., McGuire, P. (2011). Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study. Arch Gen Psychiatry, 68(5), 489-495.
• 10.Dazzan, P., Soulsby, B., Mechelli, A., Wood, S. J., Velakoulis, D., Phillips, L. J., Yung, A. R., Chitnis, X., Lin, A., Murray, R. M., McGorry, P. D., McGuire, P. K., & Pantelis, C. (2011). Volumetric Abnormalities Predating the Onset of Schizophrenia and Affective Psychoses: An MRI Study in Subjects at Ultrahigh Risk of Psychosis. Schizophr Bull. (epub 27/04/11).
• 11. Whitford TJ, Ford JM, Mathalon DH, Kubicki M, Shenton ME. (in press). Schizophrenia, Myelination, and Delayed Corollary Discharges: A Hypothesis. Schizophrenia Bulletin, doi:10.1093/schbul/sbq105.
• 12. Whitford TJ, Mathalon DH, Shenton ME, Roach BJ, Bammer R, Adcock RA, Bouix S, Kubicki M, De Siebenthal J, Rausch AC, Schneiderman JS, Ford JM. (2011). Electrophysiological and Diffusion-Tensor Imaging evidence of delayed corollary discharges in patients with schizophrenia. Psychological Medicine, 41, 959-969.

Developmental Disorders

• 1.De Luca, C. R., Wood, S. J., Anderson, V., Buchanan, J. A., Proffitt, T. M., Mahony, K., & Pantelis, C. (2003). Normative data from the CANTAB. I: development of executive function over the lifespan. J Clin Exp Neuropsychol, 25(2), 242-254.
• 2.Whittle, S., Yap, M. B., Sheeber, L., Dudgeon, P., Yucel, M., Pantelis, C., Simmons, J. G., & Allen, N. B. (2011). Hippocampal volume and sensitivity to maternal aggressive behavior: A prospective study of adolescent depressive symptoms. Dev Psychopathol, 23(1), 115-129.
• 3.Whittle, S., Yap, M. B., Yücel, M., Fornito, A., Simmons, J. G., Barrett, A., Sheeber, L., & Allen, N. B. (2008). Prefrontal and amygdala volumes are related to adolescents' affective behaviors during parent-adolescent interactions. Proc Natl Acad Sci U S A, 105(9), 3652-3657.
• 4.Yap, M. B., Whittle, S., Yücel, M., Sheeber, L., Pantelis, C., Simmons, J. G., & Allen, N. B. (2008). Interaction of parenting experiences and brain structure in the prediction of depressive symptoms in adolescents. Arch Gen Psychiatry, 65(12), 1377-1385.
• 5.Testa, R., Pantelis, C., & Fontenelle, L. F. (2011). Hoarding behaviors in children with learning disabilities. J Child Neurol, 26(5), 574-579.