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.
I am a consultant psychiatrist and clinical researcher. Over the last 15 years I have been trying to detect people at risk of development of schizophrenia and other psychotic disorders by the prospective identification of the prodromal phase of these diso
Neural Connectivity In Young People At High Risk Of Developing Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$331,972.00
Summary
This project will investigate whether or not young people at high risk of developing psychosis show irregularities in the connections between different parts of their brain. It will also investigate whether information about a high-risk individual’s brain connectivity can be used to predict a) whether that person will make the transition to psychosis, and b) their clinical prognosis if they do become psychotic.
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.
Modelling The Characteristics And Symptoms In First-episode Psychosis From Baseline To Long-term Follow-up
Funder
National Health and Medical Research Council
Funding Amount
$22,257.00
Summary
Relatively little is known about the progression of first-episode psychosis over the longer term. This research will investigate the course and evolution of psychiatric symptoms in over 600 psychotic patients up to 10 years following initial admission. It may be possible to identify groupings of patients with similar patterns of change in symptoms, along with factors underlying different patterns of symptom course, which may help distinguish the fundamental mechanisms underlying psychosis.
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
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
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
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
Acceptance And Commitment Therapy For Medication-resistant Psychosis: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$558,200.00
Summary
In spite of advances in medication, approximately one third of people with schizophrenia continue to experience distressing symptoms such as hearing voices and paranoia. Psychological 'talking treatments' are effective in helping people to cope with and be less distressed by these experiences. This study will be the first trial of a new psychological treatment, called Acceptance and Commitment Therapy, which may be more effective, briefer and more easily provided than existing approaches.