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
Identification Of Schizophrenia Susceptibility Genes: A Collaborative Project With The University Of Indonesia
Funder
National Health and Medical Research Council
Funding Amount
$546,825.00
Summary
Schizophrenia is present in all populations at a similar incidence. The project aims to identify genetic risk factors in three genomic regions previously detected by us in a genome-scan for genetic linkage in 152 Indonesian families. Colleagues at the University of Indonesia will collect an additional sample of 2000 individuals for replication. This sample will be available for research in Australia. Knowledge of risk factors will aid in diagnosis, prevention, and development of novel therapies.
Memory, Synaptic Plasticity And Gene Networks In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$1,142,138.00
Summary
Schizophrenia affects about 1% of the population. Its typical progression over a lifetime leads to long-term impairment of cognition, reality distortion, and an impoverished quality of life. Most likely, multiple genes, interacting together or with environmental factors, are involved. Using a novel approach to its partition, WA researchers aim to unravel complex networks of genes affecting memory and brain function in a cognitive deficit subtype of schizophrenia they have identified recently.
Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a grade ....Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a graded susceptibility to schizophrenia. During the last three years we have recruited a large number of families with at least one family member diagnosed with schizophrenia. The proband and all participating first-degree relatives have been assessed with a neurocognitive test battery including measures of sustained attention, working memory, speed of information processing, auditory verbal learning and executive function. Analysis of the neurocognitive data on this sample produced strong evidence that several measures are altered in patients with schizophrenia and a proportion of their asymptomatic first-degree relatives compared to unrelated normal controls. In the study we will systematically search the human genome for DNA markers linked to these measures. This will set the stage for the systematic search and characterisation of the underlying genes. This will allow us to better understand the predisposition to develop schizophrenia. In the individual case it is likely that this vulnerability results from a high-risk combination of a number of relatively common alleles which contribute to basic neural processes.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.
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
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
Selective Estrogen Receptor Modulators (SERMs) A Potential Treatment For Psychotic Symptoms Of Schizophrenia?
Funder
National Health and Medical Research Council
Funding Amount
$701,276.00
Summary
Schizophrenia is a serious disease with increasing social and economic costs. We need new treatments to improve the life and functioning of people with schizophrenia. We have published studies showing that estrogen is potentially a new treatment for schizophrenia. New brain estrogens called Selective Estrogen Receptor Modulators have fewer side-effects than standard estrogen. We will conduct a controlled clinical trial of a SERM in 180 postmenopausal women with schizophrenia.
A Study Of Muscarinic Receptors In Brain Tissue Obtained Postmortem From Subjects With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$354,810.00
Summary
The research outlined in this proposal will examine the molecular make up of certain regions of the human brain and determine if components within those regions are altered in tissue from subjects with schizophrenia. Schizophrenia is a serious psychiatric illness that affects approximately 1% of the Australian population and the research described in this proposal seeks to help understand the cause of the illness and-or to assist in the development of new drugs with which to treat the illness. T ....The research outlined in this proposal will examine the molecular make up of certain regions of the human brain and determine if components within those regions are altered in tissue from subjects with schizophrenia. Schizophrenia is a serious psychiatric illness that affects approximately 1% of the Australian population and the research described in this proposal seeks to help understand the cause of the illness and-or to assist in the development of new drugs with which to treat the illness. The goal of the research outlined in this proposal is to determine if there are changes in specific molecules in the brain, termed muscarinic receptors. The muscarinic receptors are one way that a chemical in the brain called acetylcholine can communicate with the nerve cells in the brain. Acetylcholine is known to control important functions of the brain such as in memory, cognition and learning, all of these functions are thought to be affected in schizophrenia. Importantly, the control of all these functions involve muscarinic receptors and therefore, changes in those receptors could well produce some of the symptoms of schizophrenia. We now wish to extend our early studies which suggest there may be changes in muscarinic receptors in the brain of subjects with schizophrenia to determine which of the 5 muscarinic receptors are affected in which region of the brain by the pathology of the illness. From our existing data, we would predict that these studies will add weight to the argument that muscarinic receptors are altered in schizophrenia and provide vital information as to how drugs that target these receptors may be used to treat the illness.Read moreRead less
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.