Studies On The Expression Of Muscarinic Receptors: Implications For The Pathology Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$498,791.00
Summary
Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the population. This project will help define changes in the molecules in the brain of subjects with schizophrenia which are likely to be involved in two symptoms of the disorder, the psychoses and cognitive deficits. Understanding the cause of the cognitive deficits of schizophrenia is a high priority because they are the most disabilitating symptom of the disorder and do not respond to current drug treatments.
Longitudinal Brain Changes In First-episode Psychosis: A 10 Year Follow-up MRI Study
Funder
National Health and Medical Research Council
Funding Amount
$165,250.00
Summary
It is now widely accepted that schizophrenia is associated with changes in the structure of the brain. Until recently these structural changes were considered to predate the onset of illness and to remain static. However, our own work has suggested an alternative model, which relates schizophrenia to brain changes at specific life stages. In order to demonstrate this, we intend to acquire repeat brain images on 100 patients who were initially scanned 10 years ago at the start of their psychotic ....It is now widely accepted that schizophrenia is associated with changes in the structure of the brain. Until recently these structural changes were considered to predate the onset of illness and to remain static. However, our own work has suggested an alternative model, which relates schizophrenia to brain changes at specific life stages. In order to demonstrate this, we intend to acquire repeat brain images on 100 patients who were initially scanned 10 years ago at the start of their psychotic illness. This would be the largest follow-up study of first episode psychosis in the world, with the longest interval between the first and second brain scan. Further, for a proportion of patients we will have 3 MRI scans, at illness onset, 2-4 years post-onset, followed by a third scan at 10 years, thereby providing unique follow-up brain imaging data. Based on our own and other research, we intend to explore the relationship between progressive brain change over a ten year period and: (i) the diagnosis of the patient (schizophrenia or other disorder), (ii) the clinical and functional outcome of the patient (still chronically ill or with no further episode of psychosis), and (iii) the cognitive state of the patient (their ability to perform well on tests of memory, planning and so on). We are able to conduct this study because of the existence of an infrastructure developed to follow-up patients, with a recontact rate of 70% of those patients admitted in 1992 and 1993. In this study we seek to implement these strategies for the patients identified after 1994. The results of this study will test our ideas derived from our model of the major psychotic illnesses and may identify the structural brain changes which are associated with the development of chronic schizophrenia and other psychoses. A further novel outcome will be the inclusion of patients who have remained well and identiifying the structural correlates of a good prognosis.Read moreRead less
Intervention For Tobacco Dependence Among People With A Psychotic Illness
Funder
National Health and Medical Research Council
Funding Amount
$387,625.00
Summary
The prevalence of smoking among people with a psychiatric illness, especially schizophrenia, is greater than that in the general population. Exposure to tobacco smoke has been identified as a cause of 32 different diseases as well as a cause of fire injuries. Tobacco smoke is known to contain carcinogens, as well as nicotine and numerous other poisonous substances. An extensive body of scientific evidence shows that active cigarette smoking increases the risk of many different cancers. Smoking r ....The prevalence of smoking among people with a psychiatric illness, especially schizophrenia, is greater than that in the general population. Exposure to tobacco smoke has been identified as a cause of 32 different diseases as well as a cause of fire injuries. Tobacco smoke is known to contain carcinogens, as well as nicotine and numerous other poisonous substances. An extensive body of scientific evidence shows that active cigarette smoking increases the risk of many different cancers. Smoking related diseases rate second in frequency to suicide as the greatest contributor to early mortality in schizophrenia. Popular opinion holds that people with mental illness are lacking in motivation to change their behaviour due to the effects of their mental illness. However, a recent survey of inpatients in a psychiatric hospital in Newcastle, NSW, revealed that over a quarter of smokers were either preparing to quit or cut down on their smoking or already had taken action to reduce their smoking. The present research proposal represents the first large randomised controlled trial of an intervention for tobacco dependence among people with a mental illness. This project will compare the effectiveness of nicotine replacement therapy combined with counselling with a self-help booklet on smoking. The proposed research follows a small clinical study of the feasibility of the intervention and a small randomised controlled trial supported by the Australian Rotary Health Research Fund. The proposed study brings together the expertise of several people across Australia who have experience in treating people with mental illness and drug dependence, including tobacco dependence. The results will inform future clinical interventions for smokers with a mental illness.Read moreRead less
A Comparison Of An Integrated Psychological Intervention With 'befriending' In First-presentation Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$356,113.00
Summary
The project aims to test the efficacy of two treatments to determine whether 'integrated' psychological treatment leads to better outcomes for those individuals presenting for treatment for the first time. Neuroleptic medication is the main treatment for the positive symptoms (i.e., delusions, hallucinations and thought disorder) which typify the psychoses, including schizophrenia. Yet, there are reasons why other approaches should be investigated. Firstly, not all patients respond to medication ....The project aims to test the efficacy of two treatments to determine whether 'integrated' psychological treatment leads to better outcomes for those individuals presenting for treatment for the first time. Neuroleptic medication is the main treatment for the positive symptoms (i.e., delusions, hallucinations and thought disorder) which typify the psychoses, including schizophrenia. Yet, there are reasons why other approaches should be investigated. Firstly, not all patients respond to medications. Secondly, medication may not totally alleviate the positive symptoms, and thirdly, other aspects of the condition are not helped to any extent by medication. These aspects include negative symptoms (e.g., lack of motivation and asociality), depression, social anxiety and functioning in the various life domains, e.g., school, work and socialization. In the last 15 years a viable psychological treatment known as cognitive-behavioural therapy (CBT) has emerged. This appears to be effective in the treatment of hallucinations and delusions and has an effect over and above that produced by medication. However, such treatments have not yet been applied to treating those symptoms in first presentation psychotic patients when they are in the acute stage of their illness. It is important to determine whether CBT produces positive effects in this group and whether used in conjunction with medication it can produce greater and more rapid reductions in the level and severity of positive symptoms. Whilst CBT is expected to produce positive changes in delusions and hallucinations, the applicants believe this needs to be integrated with CBT interevention focussed on other aspects of a patient's presentation, such as negative and depressive symptoms, and also on improving functioning in various life domains.Read moreRead less
Understanding The Pathology Of Muscarinic Receptor Deficit Schizophrenia: A Biochemically Defined Form Of The Disorder.
Funder
National Health and Medical Research Council
Funding Amount
$451,804.00
Summary
Schizophrenia is a group of disorders with similar symptoms and no way of distinguishing the different disorders. In our brain collection 25% of the subjects with schizophrenia have a particular chemical deficit. Screening gene expression in people with schizophrenia, with and without this deficit will give a global picture of chemical differences between the groups. Understanding the differences between sub-groups of people with schizophrenia will aid the development of better drugs for them.
The Neurobiology Of Auditory Hallucinations: Characterisation Of Dysfunction Within A Neural Circuitry Model.
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
This is a highly innovative research proposal which is based on years of extensive research by our group. Auditory hallucinations are a prominent and potentially disabling symptom of psychosis, however it is extremely difficult to study them scientifically. Past research by our group (and other groups internationally) has indicated that an extensive network in the brain is activated whenever auditory hallucinations occur, but the source of this brain activity is unclear. It was thought that the ....This is a highly innovative research proposal which is based on years of extensive research by our group. Auditory hallucinations are a prominent and potentially disabling symptom of psychosis, however it is extremely difficult to study them scientifically. Past research by our group (and other groups internationally) has indicated that an extensive network in the brain is activated whenever auditory hallucinations occur, but the source of this brain activity is unclear. It was thought that the source may be the same brain circuits that are involved in generating inner speech or monitoring it, but our past research has ruled out these possibilities. Instead, our recent work suggests that auditory hallucinations may be associated with poorly functioning connections within central auditory processing circuits, specifically between left and right auditory association cortical regions. We conceptualise hallucinations as an abnormal and involuntary form of memory retrieval consequent to this dysfunction. Our study will pioneer methods of measuring connectivity in the brain circuits identified in our model, using a combination of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) techniques in tandem with tests of central auditory processing. We believe that sufferers may benefit from understanding the physical processes which cause hallucinations. We also believe that a better understanding of hallucinations may lead to a better understanding of schizophrenia and the psychoses, which may in turn help in the development of better ways of treating these illnesses.Read moreRead less
Evaluation Of Cognitive-behaviour Therapy For Alcohol And Other Drug Problems Among People With A Psychotic Illness
Funder
National Health and Medical Research Council
Funding Amount
$217,465.00
Summary
Abuse of alcohol and other drugs among people with a major psychiatric illness is a serious public health problem and cost-effective treatments need to be developed and assessed. The aim of this project is to evaluate the effectiveness of a counselling intervention. 180 individuals with a psychotic illness and concurrent alcohol and other drug (AOD) problems will be randomly assigned to counselling or usual treatment and followed up for a period of 12 months. The indicators of interest include: ....Abuse of alcohol and other drugs among people with a major psychiatric illness is a serious public health problem and cost-effective treatments need to be developed and assessed. The aim of this project is to evaluate the effectiveness of a counselling intervention. 180 individuals with a psychotic illness and concurrent alcohol and other drug (AOD) problems will be randomly assigned to counselling or usual treatment and followed up for a period of 12 months. The indicators of interest include: current drug use; psychiatric symptoms; self-harm; social functioning; and use of health services. Findings from the proposed study will assist in the selection of particular treatment strategies and will aid the overall development of services for people with both major mental illness and substance abuse.Read moreRead less
A TMS Study Of Cortical Plasticity In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$195,500.00
Summary
The cause of schizophrenia is uncertain. Several lines of evidence implicate abnormalities of functioning in circuits of nerve cells in the outer brain regions. Chemicals involved in these circuits are important for the capacity to learn and process new information and repeated exposure to stimuli. To date, it has been difficult to directly test the function of these circuits in patients with schizophrenia. Transcranial Magnetic Stimulation (TMS) is a non-invasive means of stimulating nerve cell ....The cause of schizophrenia is uncertain. Several lines of evidence implicate abnormalities of functioning in circuits of nerve cells in the outer brain regions. Chemicals involved in these circuits are important for the capacity to learn and process new information and repeated exposure to stimuli. To date, it has been difficult to directly test the function of these circuits in patients with schizophrenia. Transcranial Magnetic Stimulation (TMS) is a non-invasive means of stimulating nerve cells in superficial areas of the brain. During a TMS procedure, an electrical current passes through a coil placed close to the scalp. This current induces a magnetic field that stimulates electrical activity in nerves below the coil. TMS methods can be used to study the functioning of nerve cells in the brain and the way in which they respond to repeated stimuli. These methods will be used in this way to study the functioning of these circuits in patients with schizophrenia. This is likely to provide important information as to the function of these brain areas and may provide information that will guide the development of therapeutic interventions.Read moreRead less
The Relationship Between Cannabis Use And Symptoms And Relapse In Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$169,604.00
Summary
Cannabis is increasingly widely used and abused by young people. Use in young people with schizophrenia is even more extensive. There is some suggestion that this drug use is a result of their illness, ie to reduce unpleasant symptoms or feelings. Equally the drug may contribute to their psychosis. This study aims to assess the degree to which psychosis may be caused by cannabis use in vulnerable young people.
A Prospective Study Investigating Implications Of Bioactive Lipids For Diagnosis And Treatment Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$324,480.00
Summary
This study will investigate the role of fatty acids (lipids) in schizophrenia. Studies in blood cells and in the brains of patients with schizophrenia have shown that these lipids and related products are altered in schizophrenia. We are now able to measure separate lipid metabolites in the living human brain using a technique called magnetic resonance spectroscopy. Until recently it was only possible to assess lipid metabolites as a group, limiting interpretation. Thanks to a newly available im ....This study will investigate the role of fatty acids (lipids) in schizophrenia. Studies in blood cells and in the brains of patients with schizophrenia have shown that these lipids and related products are altered in schizophrenia. We are now able to measure separate lipid metabolites in the living human brain using a technique called magnetic resonance spectroscopy. Until recently it was only possible to assess lipid metabolites as a group, limiting interpretation. Thanks to a newly available imaging system at the Brain Imaging Research Institute and a new analysis technique, we will be able to measure single lipid metabolites in the living human brain. Simultaneously we will also measure lipids and related enzymes in red blood cells that are responsible for the regulation of these lipids. Preliminary data has shown that there is a strong correlation between these two measures. Furthermore we will investigate the genes that are responsible for the production of these enzymes. By repeating the same tests after 12 weeks we hope to understand how the newer antipsychotic drugs act. Two easy clinical tests (a skin and breath test) will help us to implement the findings in daily clinical practice (diagnostic markers for patients at risk) . With such a multi-level approach we hope to contribute to a new understanding of the origins of schizophrenia going beyond the traditional concepts. The findings might also have direct implications for treatment. Preliminary results are very promising but also contradictory. Therefore it is even more important to carefully investigate the role of these lipids in schizophrenia.Read moreRead less