Paul Anderson
University of Melbourne, VIC
Ian Scott PhD Scholarship
Mental Health 2011
My undergraduate studies were at the University of Adelaide were I undertook a double degree; a B.A. majoring in psychology and philosophy and a B.Sc. majoring in physiology and pharmacology. I initially intended on becoming a psychologist but was drawn to investigating the fundamental biololgical processes that underlie consciousness and awareness; as such I have pursued a career as a neuroscienctist.
I undertook my honours in pharmacology (also at the University of Adelaide) with a behavioural neuroscience study investigating the hyperthermic effects of MDMA in rats. With this work I successfully demonstrated that the hyperthermic response to MDMA is mediated in part by an inflammatory process, as opposed to a purely neural pathway as was previously thought. I also showed that inhibiting microglial activation (through the administration of minocycline, an antibiotic with glial-inhibiting properties) can attenuate this hyperthermic response, a finding with potential clinical significance in treating MDMA toxicity as well as relevance to other hyperthermia inducing disease states such as stroke. Following my honours year I worked briefly as a research assistant where I contributed to a pre-clinical study on a potential drug for the treatment of chronic pain.
Following honours I moved to Melbourne to begin my PhD in the epilepsy and neuropharmacology laboratory of Prof. Terence O’Brien in the department of Medicine at the University of Melbourne. I have begun a project under Dr. Nigel Jones examining the electrophysiological correlates of psychosis; my broad background in psychology, physiology and pharmacology gives me a great strength for translational research and we aim to use animal models to facilitate future human studies. This project has the potential to add to schizophrenia research in many ways, from understanding the basic mechanisms that lad to the disruption of cognitive processes seen in the disease, to enhancing understanding of the methods of action of antipsychotic medications and providing new methods of assessing both the efficacy of novel treatments and progression of the disease.
SUMMARY OF PROJECT:
Gamma frequency oscillations and the NMDA receptor hypofunction hypothesis of schizophrenia: Exploring functional disconnections in psychosis.
This project aims to investigate how disruptions in coordinated brain activity relate to schizophrenia and psychosis, in both animal and human models of psychosis and in patients with schizophrenia. Our major experimental method is the analysis of electroencephalograms (EEGs) to examine high frequency (30-100 Hz) or ‘gamma’ brain waves, which have been shown to play a key role in working memory, attention and consciousness. These key cognitive functions are also all disrupted in patients with schizophrenia. Theories of the mechanisms underlying schizophrenia have shifter towards disorders of the NMDA receptor system, which can be modelled in humans and animals by the administration of NMDA receptor antagonists (PCP, ketamine, MK-801). These substances cause thought disorder, memory and attention problems, hallucinations and importantly disturbances in gamma frequency brain activity, mirroring the symptoms of schizophrenia.
This project aims to use animal models to examine the effects of NMDA receptor dysfunction via the administration of the NMDA antagonist ketamine, while characterising the effects on gamma frequency brain activity. We will also examine the effects of anti-psychotic drugs on gamma activity and whether they can inhibit or prevent the changes induced by ketamine.
We aim to expand these animal studies to human experiments, verifying that the techniques and methods used also work in human subjects and that the observed effects of NMDA antagonists and anti-psychotic drugs on gamma frequency brain activity in rodents translates to humans. Finally we wish to apply the research to patients with schizophrenia to further validate these animal and human models of schizophrenia and potentially develop electrophysiological correlates of psychosis that could one day play a role in the diagnosis and treatment of schizophrenia.