Cognitive Control And Brain Connectivity Disturbances In Schizophrenia And Obsessive-compulsive: Clarifying Their Nature, Specificity, And Consequences
Funder
National Health and Medical Research Council
Funding Amount
$498,337.00
Summary
Deficits of behavioural control are chronic and debilitating features of both schizophrenia and OCD. As behavioural control depends on activity within many key regions of the brain, these deficits may result not only from dysfunction within one or more region, but also from abnormal interactions between them. By studying how the activity in one region depends on another, and comparing findings between disorders, a better understanding of brain function in schizophrenia and OCD can be established
From Linkage To Genes Conferring Susceptibility To Schizophrenia: Investigation Of Candidate Genes On Chromosome 6p
Funder
National Health and Medical Research Council
Funding Amount
$462,250.00
Summary
Schizophrenia is a potentially disabling disorder with severe impact on the individual, the family and the community. The risk that a child born today will develop schizophrenia is about 1%. Genetic factors play a major predisposing role in schizophrenia, but environmental factors contribute as well. The molecular causes of schizophrenia are yet to be discovered, as knowledge about complex brain functions and their disorders is rapidly increasing. The identification and characterisation of genet ....Schizophrenia is a potentially disabling disorder with severe impact on the individual, the family and the community. The risk that a child born today will develop schizophrenia is about 1%. Genetic factors play a major predisposing role in schizophrenia, but environmental factors contribute as well. The molecular causes of schizophrenia are yet to be discovered, as knowledge about complex brain functions and their disorders is rapidly increasing. The identification and characterisation of genetic factors involved in brain function and dysfunction is likely to bring about novel insights into the neural and molecular mechanisms underlying schizophrenia. There is evidence, reported by several groups including our own, that genes, co-segregating with schizophrenia in families are located in a region on chromosome 6p. By fine-grain genetic dissection of this region, we and others have found that the gene coding for the protein dysbindin is associated with schizophrenia. Our aim is to identify the DNA variant(s) in the dysbindin gene, as well as variants in other candidate genes that may be located in chromosome 6p. We will use state-of-the art methods and information on genes and DNA variants, made available through the Human Genome Project. Once genetic variants are identified, we will analyse gene expression in post mortem brain tissue of persons with schizophrenia and study the distribution and function of the proteins coded by the identified genes. Our ultimate goal is to identify specific genetic factors involved in the brain dysfunction characterising schizophrenia. If successful, this should lead to clues about the causes of the disorder. In addition, the study will contribute to the development of methods for early diagnosis and prevention. Possibly, the most important outcome will be the identification of molecular targets for novel and more specific pharmacological treatments that may eventually replace current symptom-oriented antipsychotic medications.Read moreRead less
Schizophrenia affects, on average, 1% of the population over a lifetime and accounts for 2.6% of the global burden of disease and disability, according to a joint study by the World Health Organization and the World Bank. It is a complex disorder involving both genetic and environmental risk factors, but the specific causation remains poorly understood. People with schizophrenia experience symptoms such as delusions and hallucinations, distorted perception of reality, and progressive loss of mot ....Schizophrenia affects, on average, 1% of the population over a lifetime and accounts for 2.6% of the global burden of disease and disability, according to a joint study by the World Health Organization and the World Bank. It is a complex disorder involving both genetic and environmental risk factors, but the specific causation remains poorly understood. People with schizophrenia experience symptoms such as delusions and hallucinations, distorted perception of reality, and progressive loss of motivation, which disrupt personal development. Recent research demonstrates that underlying cognitive impairments, affecting reasoning, memory, planning ability and information processing, are at the core of the disorder and account for a high proportion of these handicaps. In a study involving 112 families with members suffering from schizophrenia, Western Australian researchers carried out detailed investigations of brain cognitive functioning, coupled with a complete genome scan. They identified, in about 50% of these families, a variety of schizophrenia characterized by multiple cognitive deficits, which turned out to be linked to a particular segment of chromosome 6. It was exactly in the chromosomal region where US investigators had previously found genetic linkage with the symptoms of schizophrenia in a large series of Irish families. In this project, the Western Australian and US teams, together with a group of Dutch researchers, will embark on a joint search for the gene (or genes) on chromosome 6, contributing to cognitive deficits in schizophrenia. They will assess a further large series of patients and controls, and conduct molecular genetic studies aiming to pinpoint the specific gene defect or variant. If successful, the project will have far-reaching implications for defining novel drug targets and treatment strategies for this disabling disorder.Read moreRead less