University of Newcastle, Australia
Schizophrenia As A Cognitive Disorder: Insights From Cognitive Neuroscience
Despite diagnostic emphasis on positive and negative symptoms, cognitive deficits and decline in functioning are core to schizophrenia. I will focus on an ERP measure of deviance detection in audition, mismatch negativity (MMN), in combination with other neuroimaging methodologies, pharmacological studies and animal models, to demonstrate what insights have been revealed about schizophrenia. Following our initial reports that MMN amplitude to simple duration deviants is reduced in schizophrenia, many research groups subsequently documented that reduced MMN is substantial in schizophrenia, and arguably one of the most robust neurobiological findings in the literature. In addition, while data on the relationship of MMN to cognitive deficits is still scant, there is strong evidence that MMN is related to general, social and occupational functioning, a relationship that our research suggests is mediated by grey matter loss in anterior regions. One reason why MMN has attracted so much attention is evidence of its dependence on the glutamate NMDAR system, providing a link to PCP-models of schizophrenia: NMDAR antagonists such as PCP not only induce psychotic and cognitive changes in healthy people that parallel schizophrenia symptoms, they also reduce MMN in humans and animals. Other evidence from our group (not universally replicated) that reduced MMN precedes the onset of the illness, is present in those identified as at risk of developing psychosis and in first degree relatives of patients, indicate that MMN meets criteria for an endophenotype for schizophrenia and is therefore a good candidate marker in animal models of the disorder. Our most recent research utilising two animal models, maternal immune activation, a risk factor for schizophrenia, and NMDAR antagonist challenge, demonstrates that MMN is affected in both models, although not quite in the manner expected. The MMN story has therefore recently become somewhat more complicated - but nonetheless informative.
Professor Pat Michie is Emeritus Professor of Psychology at the University of Newcastle having retired in May 2009. Prior to retirement, she held the positions of Acting Deputy Vice Chancellor (Research), Pro-Vice Chancellor (Research), and Professor of Psychology at the University of Newcastle. Prof Michie previously held professorial positions at the University of Western Australia and Macquarie University. Prof Michie’s primary research area is cognitive neuroscience, particularly the neural basis of auditory information processing, attention and executive functions in healthy individuals, in people with schizophrenia and those at risk of psychosis. Since retirement, she has moved into the area of animal models of schizophrenia and works full-time in research with no administrative or teaching responsibilities. She has on-going research collaborators with numerous colleagues at the University of Newcastle, and with other Australian researchers based in Perth, Sydney, Wollongong, Melbourne and Brisbane as well international researchers in Finland and Japan.