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
High-Throughput Screening Of The Genome And Proteome In Postmortem CNS From Subjects With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$553,190.00
Summary
Schizophrenia is a serious psychiatric illness that effects ~1% of the Australia population. The underlying pathology of the illness remains unknown. This application seeks funding to use new technologies to screen approximately 60% of the expressed human genome and proteome to determine which genes are being differentially expressed in two regions thought to be important in generating the symptoms of the illness, the frontal cortex and hippocampus. This project will generate a large amount of d ....Schizophrenia is a serious psychiatric illness that effects ~1% of the Australia population. The underlying pathology of the illness remains unknown. This application seeks funding to use new technologies to screen approximately 60% of the expressed human genome and proteome to determine which genes are being differentially expressed in two regions thought to be important in generating the symptoms of the illness, the frontal cortex and hippocampus. This project will generate a large amount of data, however by comparing the data from subjects with schizophrenia to that from control subjects and subjects with bipolar disorder who were psychotic and being treated with antipsychotic drugs close to death will allow us to identify changes that are specific to schizophrenia. Genes that are expressing different levels of mRNA and protein will become prime targets for future investigations as they are likely to be central to the pathology of the illness.Read moreRead less
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.
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
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.
Using Reward-based Biomarkers To Improve The Early Detection Of Bipolar Disorder In Individuals Seeking Treatment For Depression
Funder
National Health and Medical Research Council
Funding Amount
$366,252.00
Summary
Bipolar disorder is often misdiagnosed as unipolar major depression, which can have disastrous clinical consequences. Emerging evidence indicates that individuals with bipolar disorder show particular dysfunctions within brain regions involved in processing reward. This research will use cutting-edge neuroscience methodologies to investigate reward processing in these two disorders, with the objective of identifying biological markers that help distinguish bipolar from unipolar depression.
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.
Brain Connectivity Imaging Markers To Confirm Diagnosis For Bipolar Vs. Unipolar Depression – A Connectome Approach.
Funder
National Health and Medical Research Council
Funding Amount
$434,369.00
Summary
Differentiating Bipolar disorders from Unipolar Depression is a major clinical challenge. This misdiagnosis hinders optimal clinical care and has many deleterious consequences such self-harm, increased chances of suicide, poor prognosis, and greater health care costs related to this disorder. This project will provide urgently-needed advance in accurate identification of Bipolar disorders using Magnetic Resonance Imaging and remove one of the key obstacles to accurate diagnosis.
Reconceptualising Neurophysiological Biomarkers Of Schizophrenia: An Investigation Of The MMN/P3a Complex In Early Psychotic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$46,733.00
Summary
I am measuring a brain response to subtle changes in the environment called �mismatch negativity�. MMN indexes fundamental sensory processes that help the brain focus on certain information and ignore other information. MMN is consistently impaired in patients with Schizophrenia and is thought to be a biomarker of this illness. I am assessing MMN in the very early stages of psychosis to determine its specificity and whether it predicts illness trajectory.