A Genome-wide Linkage Study Of Schizophrenia In A Large Sample From Tamil Nadu, India
Funder
National Health and Medical Research Council
Funding Amount
$500,000.00
Summary
A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling familie ....A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling families, together with 400 trio families (both parents, plus their affected child). A genome-wide scan of the genetic code in all individuals will be conducted to identify chromosomal regions linked to schizophrenia. This is the first necessary step toward identifying schizophrenia susceptibility genes. If one or more genes are discovered, this will greatly improve our understanding of this disease. It will also stimulate the search for similar genes in other samples world-wide, including Australia where schizophrenia costs $2.5 billion annually in terms of treatment and loss of employment. With such a discovery, it may be possible to find better treatments that correct the basic cause of the illness and identify factors that protect against the illness.Read moreRead less
A Genetic Study Of Schizophrenia In The Brahmin Of Tamil Nadu
Funder
National Health and Medical Research Council
Funding Amount
$267,226.00
Summary
The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how it is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. Societies such as Australia are genetically diverse because people from many different ethnic groups have intermarried. To detect susceptibility genes in this type of population, we must study very large patient samples. Alternatively, we can ....The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how it is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. Societies such as Australia are genetically diverse because people from many different ethnic groups have intermarried. To detect susceptibility genes in this type of population, we must study very large patient samples. Alternatively, we can study genetically homogenous patient samples, found in isolated gene-pool populations. One such population is the Brahmin people in Tamil Nadu, a south-eastern state of India. The Brahmin are descended from the Aryan peoples who migrated into southern India 2000 years ago. In the Hindu caste system, Brahmin are the highly educated priest class, and enjoy a privileged position in society. Traditionally, marriages among the Brahmin of Tamil Nadu have been prearranged, with a preference for first-cousin marriages. As well as this cultural and historical evidence, genetic marker studies confirm that this population is a suitable genetic isolate. In this project, genetic material (DNA) will be collected from Brahmin schizophrenic patients and their families. Diagnostic data, detailed family data, and blood samples will be gathered from 90-100 extended families, each containing two or more ill individuals. Analysis of their genetic code will enable a search for possible schizophrenia susceptibility genes and a systematic search for a mutation. If found, this will greatly improve our understanding of schizophrenia, and stimulate the search for similar genes in other samples world-wide, including Australia where schizophrenia costs $3 billion annually in terms of treatment and lost jobs. If schizophrenia genes can be found, it may be possible to find better treatments that correct the basic causes of the illness and identify factors that protect against the illness.Read moreRead less
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.
Investigating The Action Of Clozapine On The Epidermal Growth Factor System: Implications For Antipsychotic Drug Action
Funder
National Health and Medical Research Council
Funding Amount
$364,535.00
Summary
Current treatments for schizophrenia are ineffective for up to half of sufferers leaving the toxic drug clozapine as the only resort. This project aims to investigate if the unique effectiveness of clozapine is due to a novel action in brain cells that we have identified. The project will delineate this mechanism and from this may lead to the development of a new way of treating schizophrenia and insights into the causes of this disorder.
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
Outcome Prediction, Stratification And Novel Treatments In Individuals At Ultra High Risk Of Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
The Ultra High Risk (UHR) criteria have been developed to identify people at high risk of psychotic disorders such as schizophrenia so that treatments can be provided early to reduce risk and disability. However the some UHR people are at risk of other difficulties and disorders and others are not at risk of all. We need to improve our ability to distinguish between these groups so that treatment can be tailored according to risk, and develop new treatments that target underlying problems.
Identifying EQTLs And Endophenotyping Known CNVs In A Large Australian Schizophrenia Sample
Funder
National Health and Medical Research Council
Funding Amount
$902,472.00
Summary
This study hopes to identify genetic code variations associated with an increased risk of schizophrenia . We will study variation in gene expression levels in patients and healthy controls to identify underlying changes in the genetic code responsible. In a subset of patients with schizophrenia and known rare copy number variations (CNVs) in the genetic code we will conduct brain scans and psychological tests to characterize the effect of CNVs on brain structure and function in schizophrenia.
Attentional Effects On Prepulse Inhibition Of The Acoustic Startle Reflex In Patients With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$278,625.00
Summary
People suffering from schizophrenia exhibit differences from healthy people in the startle reflex, which is a blink of the eyes when a sudden loud sound occurs. Normally, this reflex is reduced in size when a quiet sound occurs a few milliseconds before the startling sound, but this prepulse inhibition of the startle reflex or PPI does not occur to the same degree in people with schizophrenia. The underlying causes of this reduction in PPI in patients with schizophrenia is not known. The most co ....People suffering from schizophrenia exhibit differences from healthy people in the startle reflex, which is a blink of the eyes when a sudden loud sound occurs. Normally, this reflex is reduced in size when a quiet sound occurs a few milliseconds before the startling sound, but this prepulse inhibition of the startle reflex or PPI does not occur to the same degree in people with schizophrenia. The underlying causes of this reduction in PPI in patients with schizophrenia is not known. The most commonly accepted theory is that it reflects a deficit in a basic sensorimotor gating function which could underlie a variety of attentional abnormalities observed in schizophrenia. However, our data indicate that patients exhibit more PPI when they ignore the prepulse stimuli. We wish to test the hypothesis that alterations in PPI in schizophrenic patients are secondary to abnormalities in attention. This is significant because the theory can point to a specific cognitive deficit associated with schizophrenia. We have also found that patients treated with some kinds of antipsychotic medications (the newer atypical antipsychotic medications) do not show reductions in PPI, but patients treated with older types of antipsychotic drug do show reductions in PPI. We intend to investigate the effects of different types of antipsychotics on attentional modulation of PPI. This is significant because it may indicate that patients with a specific kind of cognitive impairment may show improvement with a specific type of medicine. Our data suggests that chronic cannabis use may associated with differences in the startle reflex and in PPI. Understanding how such cannabis use alters PPI may provide insights into why so many people with schizophrenia regularly abuse cannabis.Read moreRead less