Schizophrenia & Affective Disorders
We have been developing and using newer imaging analysis techniques to study these conditions cross-sectionally and longitudinally. The work in this stream has been in close collaboration with Prof McGorry, A/Prof Alison Yung, Dr Lisa Phillips and their colleagues at ORYGEN Research Centre. Increasingly, we are also taking a brain maturational perspective to understanding these dynamic brain changes in psychosis (this is further elaborated in the Adolescent Development of Brain & Behaviour stream).
Progressive brain changes in psychosis
Dr Daqiang Sun, co-supervised by A/Prof Geoff Stuart, undertook longitudinal MRI studies as part of his successful PhD thesis. They demonstrated that such changes are dependent on both the stage of maturation of the brain and the age at which the illness develops, and that the observed changes are relevant to understanding functional deficits. More recently, Dr Sun has been working at UCLA in Prof Tyrone Cannon’s lab. This productive collaboration with Prof Cannon, Prof Paul Thompson and their colleagues at UCLA (USA) is further exploring brain changes in these early illness stages using sophisticated methods developed in their lab. Dr Stephen Wood has been undertaking a range of research projects in schizophrenia at its earliest stages, including investigations of memory and brain imaging studies. His expertise in using Magnetic Resonance Spectroscopy (MRS) has provided insights into the chemistry of the living brain. An important study from this work has identified that N-acetyl-aspartate (NAA: a marker of neurons) levels in the dorsal part of the brain’s frontal lobe at the onset of schizophrenia predicts outcome at two years. This work was accepted for publication in the Archives of General Psychiatry. In an NH&MRC funded study, Dr Dennis Velakoulis and Dr Stephen Wood, Casey O’Brien and colleagues from ORYGEN Research Centre have completed an investigation examining brain imaging and neuropsychological changes 10 years after a first psychosis episode. Preliminary findings will be presented at the International Congress of Schizophrenia Research (ICOSR) in 2007.
Stress, HPA function and pituitary volume
In collaboration with Dr Carmine Pariante and colleagues from London’s Institute of Psychiatry as well as colleagues from Athens, we have investigated the role of stress in explaining brain changes during illness onset. In seminal publications this work has demonstrated that enlarged pituitary volumes are apparent in the high-risk individuals who subsequently develop psychosis and in first-episode psychosis patients. The enlarged pituitary is considered to reflect abnormal HPA function related to stress hormones, which may explain the brain structural changes observed. Measures of the stress hormone cortisol are now being examined in relation to brain structural measures. Dr Belinda Garner undertook the work on pituitary size in the prepsychotic groups as part of her PhD thesis, and also looked at rat models of stress and their impact on function (in collaboration with Dr Maarten van den Buuse from MHRI).
The Australian Study of Twins with Psychosis (ASTP) is a large, multi-centre study being conducted in collaboration with Prof Bryan Mowry and colleagues from The University of Queensland. This study is concerned with identifying neuroimaging and cognitive markers of genetic vulnerability to psychotic disorders such as schizophrenia and bipolar disorder. Findings will be used to guide molecular genetic research in an attempt to identify new susceptibility genes for mental illness. Dr Gregor Berger (ORYGEN) has also established a biobank for genetic material, which will allow us to assess how genetics are related to the abnormal brain indices identified in schizophrenia and psychosis.
Together with Prof Michael Berk and other colleagues from Barwon Health, researchers from MNC are about to commence a study investigating the neuroanatomical and neuropsychological changes in bipolar disorder. This project aims to investigate whether there are any correlations between cognitive performance and alterations to brain structures, in the hope of developing a greater understanding of bipolar disorder and the way in which it affects an individual’s life. Further work in bipolar disorder is underway with Dr Gin Mahli (Black Dog Institute, NSW) and Dr Sophia Frangou (IOP, London).
Dr Dennis Velakoulis, Dr Stephen Wood and colleagues have also undertaken one of the largest studies of hippocampus and amygdala size at various stages of psychosis and schizophrenia, from before illness onset. This study was accepted by Archives of General Psychiatry and shows that smaller hippocampus is found in established schizophrenia while enlarged amygdala are found in non-schizophrenic psychoses. Dr Mark Walterfang and Dr Marc Seal are also undertaking a series of studies examining white matter changes in schizophrenia and early psychosis in a number of collaborations including Monash Neurosciences, Brain Research Institute, University of Queensland, and colleagues from Toyama University (Japan). As part of his PhD thesis, Dr Mark Walterfang has examined the major white matter tracts connecting the two sides of the brain, the corpus callosum. He has shown that abnormalities are evident prior to the onset of a psychotic episode. Further changes develop with progression of the illness, involving those areas of the callosum that connect with other brain regions implicated in schizophrenia.
The anterior cingulate cortex
Dr Murat Yücel is investigating the anterior cingulate cortex (ACC) in schizophrenia and obsessive compulsive disorder as part of an NH&MRC funded study, as well as other disorders, including depression, bipolar disorder, substance use and personality disorders (discussed further below). A number of PhD students are working closely with him on this work: Dr Ben Harrison recently completed his PhD, examining the ACC in schizophrenia from illness onset and is now undertaking a NH&MRC CJ Martin post-doctoral fellowship to pursue this work further. He is working with Prof Jesus Pujol in Barcelona and will be returning to complete his fellowship with MNC. Alex Fornito, PhD student is examining the ACC in detail comparing schizophrenia and bipolar disorder. In this series of studies he is assessing the ACC and its connections with the frontal brain regions, and is also examining the cognitive and emotional parts of the brain and how they are affected in these disorders.
Intervention and treatment
In collaboration with Dr Gregor Berger at ORYGEN Research Centre, we have been examining the neurobiological effects of interventions used in psychosis, including fish oils, lithium and various antipsychotic drugs. In collaborative work on an NH&MRC funded study headed by A/Prof Brian Dean and Dr Suresh Sundram from MHRI, we are examining the role of muscarinic receptors on cognition in schizophrenia. These receptors may be relevant to the features of the disorder and may be relevant to treatment.
Sunshine Hospital Node - Adult Mental Health Rehabilitation Unit (AMHRU)
A/Prof Robyn Hayes and Ms Deidre Bradshaw offer a unique contribution to the team by focusing on the psychosocial and behavioural aspects of mental illness and the impact that it places upon the individual, family and friends, and the community. They are seeking to understand the varied types of problems, including neuropsychological difficulties, that individuals with mental illness are experiencing by assessing their needs within the clinical settings or home environment. From this they aim to develop environmentally adaptive intervention strategies to help with these problems ‘in situ’. Dr Linda Kader is also conducting research on non-biological modes of treatment for the predominantly treatment resistant patient group in the Unit. Creative arts therapy, music therapy, and drama therapy are being evaluated. These interventions can improve therapeutic alliance, communication, engagement and risk reduction. Assessing the adverse medical effects of the newer ‘atypical’ antipsychotics has also been an important area of our research. In collaboration with A/Prof Tim Lambert (OPEN, University of Melbourne) we have investigated medical comorbidity in patients with chronic schizophrenia. We have assessed how common medical problems were found in patients, including obesity, diabetes and high levels of cholesterol and other lipids. We have also investigated the adverse effects on the heart of treatment with Clozapine. The findings suggest that Clozapine may cause cardiomyopathy, but that this is usually mild and frequently reversible. We are now working with Prof Michael Berk and colleagues at Barwon Health who have also been examining these problems. Further work is exploring the effects of antipsychotic treatments on neuropsychological function and brain structural changes.