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
Dopamine Neuron Ontogeny: Convergent Neurobiological Pathway For Risk Factors Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$337,214.00
Summary
Schizophrenia is associated with changes in dopamine (a signalling molecule in the brain). These changes are present prior to psychosis, suggesting they begin early in development. Our aims are to manipulate key factors in the development of brain dopamine systems to clarify their role in psychosis and schizophrenia. This work has the potential to identify early brain changes that lead to schizophrenia, which in turn may generate better diagnoses and outcomes for people with this disorder.
Neuregulin Dependent Neuronal Migration And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$297,128.00
Summary
Schizophrenia effects 1-100 Australians and is responsible for $2.2 billion in health costs, disables thought and emotion and is devastating to the individual, the family and the community. We need to develop drugs able to reverse the root cause of schizophrenia. We know that schizophrenia is caused by risk genes and environments and impacts brain maturation. We will test how one such gene, neuregulin, acts to derail the normal development of the human cerebral cortex in patients who suffer.
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.
Neonatal Vitamin D Status And Risk Of Schizophrenia: A Study Using Danish Dried Bloods Spots
Funder
National Health and Medical Research Council
Funding Amount
$164,980.00
Summary
There is increasing evidence that low levels of vitamin D (i.e. the 'sunshine hormone') during early development can alter brain development. In particular, it has been proposed that low vitamin D during development (e.g. prenatal and in early life), increases the risk of developing schizophrenia during adulthood. A previous study based on stored third trimester blood samples from US women suggested that very low levels of maternal vitamin D may be associated with an increased risk of schizophre ....There is increasing evidence that low levels of vitamin D (i.e. the 'sunshine hormone') during early development can alter brain development. In particular, it has been proposed that low vitamin D during development (e.g. prenatal and in early life), increases the risk of developing schizophrenia during adulthood. A previous study based on stored third trimester blood samples from US women suggested that very low levels of maternal vitamin D may be associated with an increased risk of schizophrenia in the offspring. We have the opportunity to explore this hypothesis using a large, well-described Danish 'bio-bank'. Since 1981, blood samples from newborn babies have been kept by a central agency in Denmark. In collaboration with senior Danish medical researchers, 900 blood samples of babies who have subsequently developed schizophrenia and 1800 from matched healthy individuals have been identified. We will measure vitamin D levels in these blood samples. We predict that babies with low levels of vitamin D will have an increased risk of developing schizophrenia. If low prenatal vitamin D does increase the risk of schizophrenia, this finding will have important implications from a public health perspective. Just as the number of infants affected by spina bifida has been reduced by adding folate supplements to foods, optimizing maternal vitamin D levels may lead to a reduction in the incidence of schizophrenia.Read moreRead less
An Integrated Psychoacoustic And High-field FMRI Study Of Auditory Temporal Processsing Dysfunction In Schiophrenia.
Funder
National Health and Medical Research Council
Funding Amount
$306,000.00
Summary
This research seeks to improve our understanding of the causes of brain dysfunction in schizophrenia. This chronic and debilitating psychiatric disorder is usually accompanied by dramatic symptoms such as hallucinations, delusions, paranoia and disordered patterns of thinking. Based on our interpretation of evidence from a number of fields of schizophrenia research we suspect that the brain dysfunction in schizophrenia may not in the brain areas responsible for those dramatic symptoms but occurs ....This research seeks to improve our understanding of the causes of brain dysfunction in schizophrenia. This chronic and debilitating psychiatric disorder is usually accompanied by dramatic symptoms such as hallucinations, delusions, paranoia and disordered patterns of thinking. Based on our interpretation of evidence from a number of fields of schizophrenia research we suspect that the brain dysfunction in schizophrenia may not in the brain areas responsible for those dramatic symptoms but occurs initially in the very basic sensory regions of the brain. These regions can be thought of as providing the building blocks of our perceptions, that ultimately allow us to see, hear, smell and feel. Our previous research shows that people with schizophrenia have a very specific problem in the way that they perceive sounds. Using measures of brain activity, people with schizophrenia show consistent evidence that their brains do not process some of the timing information contained in sound. This is not the same as saying that people with schizophrenia are deaf, the deficits we see are much more subtle. It's a bit like the chaos theory analogy of a butterfly fluttering in Brazil and causing a typhoon in China. We think that very small alterations in brain activity in the initial stages of sensory processing can cascade through successively more complex stages of the brain, eventually creating the psychotic storm that becomes evident as the primary symptoms of schizophrenia. The brain regions we are interested in are located down at the base of the brain, in the brainstem, and it is only recently that the technology and methods of analysis we need to look at this activity have been developed. In this research we will be using functional magnetic resonance imaging and sophisticated hearing tests to examine whether these brain regions show the alterations we expect. If so, this will mean that the brain dysfunction in schizophrenia is quite different to what is currently believed.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