Muscarinic M1 Receptor, Cognition And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$598,800.00
Summary
Schizophrenia is a serious psychiatric illness that affects approximately 1% of Australia's population. Whilst the prominent symptom of schizophrenia is psychosis, the majority of subjects with schizophrenia also show deficits in cognition. Unlike psychotic symptoms, deficits in cognition do not respond well to current antipsychotic drug treatment. We have been investigating the possible role for changes in a family of receptors, called muscarinic receptors, in the pathology of schizophrenia for ....Schizophrenia is a serious psychiatric illness that affects approximately 1% of Australia's population. Whilst the prominent symptom of schizophrenia is psychosis, the majority of subjects with schizophrenia also show deficits in cognition. Unlike psychotic symptoms, deficits in cognition do not respond well to current antipsychotic drug treatment. We have been investigating the possible role for changes in a family of receptors, called muscarinic receptors, in the pathology of schizophrenia for almost a decade. Our research has shown that two members of the muscarinic receptor family, the M1 and M4 receptors, may be differentially decreased in different brain regions of subjects with schizophrenia. Recently, we have shown that in the dorsolateral prefrontal cortex, the muscarinic receptor that is decreased in schizophrenia is the M1 receptor. Since we made this discovery another group has shown that a mutation in the M1 receptor may be a cause of cognitive deficits in schizophrenia. We are now proposing a study using parallel streams of research on postmortem brain tissue and in living subjects with schizophrenia to determine the likelihood that decreases in M1 receptors in the cortex may be the cause of cognitive deficits in schizophrenia. This will involve confirming that mutations in the M1 receptor, measured using DNA from white blood cells, are associated with cognitive deficits in schizophrenia. At the same time we will determine if the same mutation is associated with low levels of M1 receptors in cortex obtained postmortem from subjects with schizophrenia. If both these are true this will give us a strong platform to suggest that low levels of cortical M1 receptors are associated with cognitive deficits in schizophrenia.Read moreRead less
Cognitive Enhancement In Schizophrenia Via Selective Oestrogen Receptor Modulator.
Funder
National Health and Medical Research Council
Funding Amount
$396,380.00
Summary
Cognitive dysfunction in schizophrenia is resistant to treatment and related to poor community functioning and quality of life. In spite of the widely appreciated magnitude of the problem, there is still a critical gap in our knowledge concerning treatments to reverse these cognitive deficits. The proposed research is significant because it will clarify the role of hormones and genes in relation to cognitive deficits in schizophrenia and it may help patients improve their level of functioning.
Tailoring Adjunct Glycine Therapy In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$447,353.00
Summary
‘Glycine’ is an amino acid that can be purchased ‘over the counter’ at health food shops in Australia. Although traditionally administered as a dietary supplement, recently there has been considerable excitement in the psychiatric community due to its ability to improve schizophrenia symptoms when administered in conjunction with mainstream medications. However, two issues need to be resolved in order for glycine to be employed as a routine therapy in schizophrenia. Firstly, this treatment is on ....‘Glycine’ is an amino acid that can be purchased ‘over the counter’ at health food shops in Australia. Although traditionally administered as a dietary supplement, recently there has been considerable excitement in the psychiatric community due to its ability to improve schizophrenia symptoms when administered in conjunction with mainstream medications. However, two issues need to be resolved in order for glycine to be employed as a routine therapy in schizophrenia. Firstly, this treatment is only effective in some patients, and we have no way of determining which patients will benefit from glycine. Secondly, there are both theoretical reasons and experimental evidence that glycine administration can cause severe impairment for some individuals. Thus although there is great potential for glycine to ease the burden of schizophrenia symptoms, these two issues need to be resolved before this possibility can be actualised. Theoretical considerations, supported by pilot research of the investigators, point to the view that schizophrenia patients’ baseline glycine level is the critical factor that determines whether a patient will benefit or be impaired by glycine therapy. This thesis offers a testable means with which to resolve the above limitations to the use of glycine. The purpose of the current research program is thus to provide the basis for rational prescription of glycine as an additional therapeutic tool in schizophrenia.Read moreRead less
I have established and head the Melbourne Neuropsychiatry Centre within the University of Melbourne. My university position is a research chair with the specific aim of leading a team of researchers in neuropsychiatric research. One of the goals of the Centre is to deliver world-class neuroimaging research in psychiatric disorders. I head a team of researchers that have been undertaking neuroimaging and neuropsychological work on schizophrenia and psychosis since 1993 in Australia. My particular ....I have established and head the Melbourne Neuropsychiatry Centre within the University of Melbourne. My university position is a research chair with the specific aim of leading a team of researchers in neuropsychiatric research. One of the goals of the Centre is to deliver world-class neuroimaging research in psychiatric disorders. I head a team of researchers that have been undertaking neuroimaging and neuropsychological work on schizophrenia and psychosis since 1993 in Australia. My particular interest and impact on the field has been to define and understand progressive brain changes in schizophrenia and related psychotic disorders. Further work will place these changes within a brain maturational context, particularly examining trajectories of development in adolescence and young adulthood.Read moreRead less
Schizophrenia is a serious and debilitating psychotic illness often characterized by delusions: fixed, false beliefs that preoccupy the patient and affect behaviour, and which are resistant to current drug treatments. This project investigates dysfunctions in belief mechanisms that allow delusions to form and be maintained. This will help clinicians design more effective programs of cognitive behavioural therapy for psychosis by allowing more focussed interventions to reduce delusions.
Motor Passivity Symptoms In Schizophrenia And Mental Representations Of The Body
Funder
National Health and Medical Research Council
Funding Amount
$220,180.00
Summary
Individuals with schizophrenia who report passivity symptoms feel that they are no longer in control of their movements and believe that their actions may be willed by some other power. This research aims to examine a set of mental processes which determine how the body is 'represented' in the brain and which, if disrupted, can lead to disorders of body experiences. The outcome of the study will lead to a greater understanding of passivity symptoms and can be used to plan interventions.
Anatomical Substrates For Primate Executive Cortical Function
Funder
National Health and Medical Research Council
Funding Amount
$362,820.00
Summary
When studying the brain, many have been tempted to look for similarities in organization of cells and circuitry in different regions involved in various processes. While, at a first approximation, this may be a reasonable approach to understand how the brain works, it also ignores what makes the brain so complex: the diversity in its structure. In the late 19th, and early 20th, centuries, pioneering anatomists seized on the diversity in structure of the human brain. The study of cortical circuit ....When studying the brain, many have been tempted to look for similarities in organization of cells and circuitry in different regions involved in various processes. While, at a first approximation, this may be a reasonable approach to understand how the brain works, it also ignores what makes the brain so complex: the diversity in its structure. In the late 19th, and early 20th, centuries, pioneering anatomists seized on the diversity in structure of the human brain. The study of cortical circuitry that underlies the diversity in cortical processing reached a zenith and there was a renaissance in understanding of brain function. These researchers were, however, limited by techniques available to them at the time. With the advent of new methodologies which allowed scientists to explore individual connections between cells (synapses), to probe structure and transmission across synapses, and to record from live neurones, new and exciting discoveries were made. However, these methodologies are highly time consuming and studies became necessarily more focussed. As a result, there was a tendency in the later half of the 20th century to extrapolate findings from one cortical area to cortex in general. Even more precarious, anatomical and functional findings in highly specialized sensory cortex of one species were projected to other distantly related species. Such thinking lead to a dark age in neuroscience. It became widely accepted that there exists a canonical circuit. Consequently, differences in function between different cortical areas were attributed solely to the source of their projections. The central thesis of this project is to study aspects of cell structure and cortical circuitry in the prefrontal lobe. We hope that the project will provide another step in the pathway that leads to understanding the mind.Read moreRead less
Imaging Genetics In Schizophrenia And Bipolar Disorder: Adjudicating Neurocognitive Endophenotypes
Funder
National Health and Medical Research Council
Funding Amount
$569,873.00
Summary
Schizophrenia and bipolar disorder share some common genes and cognitive deficits, yet manifest differently in terms of symptom expression, illness course, and functional impact. This research tests the assertion that genes implicated as common to these conditions may code for impairments in prefrontal cognitive and sub-cortical emotion processing. We also examine whether between-diagnosis distinctions in these brain responses may be mediated by hypothalamic-pituitary-adrenal axis functioning.