Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the ....Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission. Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar disorder, with a heritability of the order of 80%. Yet the identification of the genetic basis of the disease has proved exceedingly difficult, with numerous studies producing no definitive data. The lack of convincing results has been interpreted as an indication of complex genetic mechanisms and underlying differences between affected families and ethnic groups. Genetically isolated populations, where most individuals descend from a small number of founders, are believed to hold great potential for understanding the genetic basis of complex diseases, such as bipolar disorder. Affected subjects in such populations are likely to share the same predisposing genes, making these genes easier to identify. During the last 10 years, we have been involved in the study of bipolar disorder in one such population, with very promising results. In this project, we propose to take the research further by collecting more affected families, confirming the current positive findings and narrowing down the search to a small region, possibly a single gene. If successful, the study will be a major breakthrough which, by identifying a molecular pathway and disease mechanism, will contribute valuable and generally valid information on the biological basis of mood disorders.Read moreRead less
Understanding The Pathophysiology Of Schizophrenia, Major Depressive Disorder And Bipolar Disorder As A Basis For Improving Treatments
Funder
National Health and Medical Research Council
Funding Amount
$804,106.00
Summary
The Applicant seeks to understand the causes of the schizophrenia, bipolar disorder and major depressive disorder, which affect over 20% of the Australian population. This research is important as drug design, based on chemical remodelling, has not significantly advanced initial breakthroughs in treating psychiatric disorders and there is now a widespread belief that new drugs will only come from understand their causes.
Understanding The Role Of Muscarinic Receptors In The Pathophysiology Of Depression And Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$480,074.00
Summary
The causes of bipolar disorder and major depressive disorder, which effect many Australians, remain unknown. We have recently shown decreases in muscarinic receptors in the brain of people with bipolar disorder and major depressive disorder. Muscarinic receptors are important in maintaining the functions of the brain that seem to be affected in people with bipolar disorder and major depressive disorder. Here we seek to understand how changes in muscarinic receptors occur in both disorders.
The Development of English Economic Vocabulary to 1776: the Formation of a Disciplinary Language. The language of economic science is fundamental to all social theory - and indeed, to how modern societies perceive themselves. Where does that vocabulary - both the language and the concepts carried by that language - come from? How did it develop? The aim of this research project is to clarify the answers to these two questions, up to the time at which political economy or economics became a matur ....The Development of English Economic Vocabulary to 1776: the Formation of a Disciplinary Language. The language of economic science is fundamental to all social theory - and indeed, to how modern societies perceive themselves. Where does that vocabulary - both the language and the concepts carried by that language - come from? How did it develop? The aim of this research project is to clarify the answers to these two questions, up to the time at which political economy or economics became a mature intellectual system - in Adam Smith's 1776 "Wealth of Nations". This will be the first such systematic and comprehensive book-length study of the formation of this disciplinary language ever attempted.Read moreRead less
Anti-Estrogens - A Potential Treatment For Bipolar Affective Disorder In Women?
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Bipolar Affective Disorder (BPAD) or Manic-Depressive Illness is a serious mental illness with high morbidity and mortality. The cause of the illness is still unclear and the underlying neurochemical changes are different for the manic phase compared with the depressive phase. The current treatments for BPAD are limited in scope and not biochemically well understood. There are gender differences in the presentation and outcomes for BPAD which adds to the complexity of the illness. We are proposi ....Bipolar Affective Disorder (BPAD) or Manic-Depressive Illness is a serious mental illness with high morbidity and mortality. The cause of the illness is still unclear and the underlying neurochemical changes are different for the manic phase compared with the depressive phase. The current treatments for BPAD are limited in scope and not biochemically well understood. There are gender differences in the presentation and outcomes for BPAD which adds to the complexity of the illness. We are proposing a study to develop a new type of treatment for the manic phase of BPAD and are exploring the use of anti-estrogens in women with mania. The background to our proposed study comes from a few case reports suggesting that anti-estrogen agents such as progesterone and tamoxifen may be useful adjuncts to treatment. We conducted a small pilot study comparing the addition of oral tamoxifen with oral progesterone and placebo in 10 women with mania and found that the women who received tamoxifen made significantly better improvements in their manic symptoms over a 28-day trial. The research study we are now proposing is a larger, three-arm, double blind, placebo controlled, 28-day adjunctive study in women with mania to expand and clarify our pilot study findings. Patients in our proposed study would receive either 40mg per day tamoxifen or 20mg per day progesterone or placebo in addition to standardised lithium medication. We will measure enzyme activity (protein kinase C) and estrogen-progesterone levels to understand more about the mechanisms of action by these new hormone treatments. BPAD is a crippling disorder and if we are successful, then tamoxifen treatment may be an important new treatment. This proposed study will also shed new light on some of the neurochemical mechanisms underlying BPAD as well as opening up the new area of hormone treatments for serious mental illness.Read moreRead less
Differential Changes In Cortical Tumour Necrosis Factor Signalling In Mood Disorders And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$642,078.00
Summary
Changes in inflammation-related pathways contribute to the symptoms of psychiatric disorders and tumour necrosis factor ? (TNF) is a protein central to regulating theses pathways. We have now shown that changes in pathways regulated by TNF are present in the brains of people with schizophrenia and mood disorders. This means that the symptoms experienced by those with the different disorders may be linked to differential changes in TNF-regulated pathways in the brain.
Cultures of risk-taking in Renaissance Italy. This project aims to provide a cultural history of the development and nature of pre-modern capitalism that moves beyond outmoded models of linear, rational progression. The project will look at Renaissance Italy, a node in the development of modern capitalism, and analyse how merchants and gamblers took financial risks. By using risk as a category of analysis to examine the interconnections between rational and irrational decision making in sixteent ....Cultures of risk-taking in Renaissance Italy. This project aims to provide a cultural history of the development and nature of pre-modern capitalism that moves beyond outmoded models of linear, rational progression. The project will look at Renaissance Italy, a node in the development of modern capitalism, and analyse how merchants and gamblers took financial risks. By using risk as a category of analysis to examine the interconnections between rational and irrational decision making in sixteenth-century commerce and gambling, the project aims to understand the development of attitudes and values still prevalent today. The project will write irrationality into the history of modern capitalism.Read moreRead less