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
Advanced Paternal Age: Behavioural, Neuroanatomical And Genomic Correlates In The Offspring Of Older Fathers
Funder
National Health and Medical Research Council
Funding Amount
$501,565.00
Summary
The offspring of older fathers have an increased risk of developing disorders such as autism and schizophrenia. This is thought to be due to mutations in the developing sperm. Our group has shown in a mouse model that the offspring of older fathers have changes in brain shape and in behaviour, similar to some findings in autism. In this grant we will refine this animal model and explore the brain, behavioural and genetic correlates of advanced paternal age.
Schizophrenia is a group of brain disorders that affects approximately 1 in 100 people. The symptoms can include delusions (false beliefs), hallucinations (e.g., hearing voices), blunted emotions, poor planning ability and reduced motivation. Because these disorders often start in early adulthood, and can be chronic, schizophrenia contributes substantially to the burden of disease across the globe. The causes of schizophrenia are poorly understood, but it is clear that both genetic factors and e ....Schizophrenia is a group of brain disorders that affects approximately 1 in 100 people. The symptoms can include delusions (false beliefs), hallucinations (e.g., hearing voices), blunted emotions, poor planning ability and reduced motivation. Because these disorders often start in early adulthood, and can be chronic, schizophrenia contributes substantially to the burden of disease across the globe. The causes of schizophrenia are poorly understood, but it is clear that both genetic factors and environmental factors can contribute to the risk of developing schizophrenia. As part of an integrated program of research searching for novel environmental risk factors for schizophrenia, this application examines the impact of low prenatal vitamin D on brain development. Vitamin D is a steroid hormone mostly derived from the action of bright sunshine on the skin. Our past research (based on population studies, cell culture studies and animal experiments) have provided tantalizing clues about the impact of low prenatal vitamin D on brain development. This project will explore two important areas. We will explore mechanims by which LOW vitamin D may cause LESS programmed cell death (apoptosis). Programmed cell death is a crucial feature in brain development, and any alteration to the orderly sequence of brain development may leave the person vulnerable to adult-onset brain disorders like schizophrenia. Secondly, we will compare the behaviour and brain markers of adult rats born of mothers depleted of vitamin D versus normal mothers. Finally, we will examine the impact of vitamin D on neural tissue cultures obtained from nasal biopsy. If low prenatal vitamin D is a risk factor for schizophrenia, then it may be possible to reduce the incidence of schizophrenia by providing pregnant women with a safe and cheap vitamin tablet (similar to how folate supplements have reduced the incidence of spina bifida) .Read moreRead less
A Comparative Structural And Functional Cerebral MRI Study Of First Episode Schizophrenia And Long-term Cannabis Use.
Funder
National Health and Medical Research Council
Funding Amount
$373,125.00
Summary
Cannabis is used for its subjective effects that include euphoria, depersonalisation, somnolence, and altered perceptions of temporal contingency.It is a controlled substance yet one quarter of Australian adolescents and seven percent of adults use cannabis regularly. Chronic use of cannibis can impair frontal brain functioning, affecting the capacities for attention, working memory and concentration.These neurocognitive deficits bear striking similarities to those associated with the negative s ....Cannabis is used for its subjective effects that include euphoria, depersonalisation, somnolence, and altered perceptions of temporal contingency.It is a controlled substance yet one quarter of Australian adolescents and seven percent of adults use cannabis regularly. Chronic use of cannibis can impair frontal brain functioning, affecting the capacities for attention, working memory and concentration.These neurocognitive deficits bear striking similarities to those associated with the negative symptom cluster of schizophrenia,which is related to frontal brain dysfunction. The proposed study will be the first of it's kind to apply sophisticated neuroimaging techniques to investigate how long-term adolescent cannabis use effects the structure and function of the brain and to make comparative analyses with the brain changes associated with first episode schizophrenia. We predict that structural brain abnormalities that are consistent in localisation, if not in degree, will be detected in long-term cannabis using and first episode schizophreniaparticipants and that there will be even more profound abnormalities in the first episode schizophrenia cannabis users. We will use the Tower of London (TOL) task to activate certain areas associated with executive functioning (for instance attention, memory, and strategic planning). Here, we expect lower intensity activation of the prefrontal cortex during TOL performance both in the cannabis and first episode schizophrenia groups and that the activation will be lowest of all for the cannabis using first episode schizophrenia group. The methodology to be applied in this study offers a unique opportunity to enhance our understanding of the structural and functional markers of first episode schizophrenia and cannabis use in the neural substrate.Read moreRead less
INVESTIGATING THE VALIDITY OF PRENATAL INSULTS AS RISK FACTORS FOR SCHIZOPHRENIA.
Funder
National Health and Medical Research Council
Funding Amount
$201,100.00
Summary
Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical ma ....Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical make up of the brain and gives rise to long-lasting structural and neurochemical changes in adolescent animals, which resemble changes found in the brains of patients with schizophrenia. We will also assess whether behavioural responses of compromised animals are altered in tests that parallel disturbances seen in patients with schizophrenia. Such abnormal brain development could create an underlying vulnerability in the brain, predisposing individuals with risk factors such as genetic inheritance to develop the symptoms of schizophrenia in later life perhaps only after the complete formation of nerve pathways involved in higher brain functioning. If guinea pigs that have been subjected to low oxygen levels during pregnancy show sustained changes in the structure and neurochemistry in regions of the brain that are altered in patients with schizophrenia it would suggest that these long lasting disturbances could result from problems during pregnancy. Thus, this would support the idea that abnormal brain development during pregnancy is one of the underlying causes of schizophrenia.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
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.
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.
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