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
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
The Efficacy Of Adjunctive Garcinia Mangostana Linn. Pericarp For Bipolar Depression: A 24-week Double-blind, Randomized, Placebo-controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$1,227,272.00
Summary
Bipolar disorder, especially during episodes of depression, can be highly debilitating. There is scientific evidence now directing research towards new targets to produce new therapies for bipolar depression. The current study aims to utilise an entirely new agent made from the husk of the mangosteen fruit (mangosteen pericarp). Mangosteen pericarp has properties that we believe will assist in reducing symptoms for those with bipolar depression, when taken in addition to usual treatment.
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
A Double-blind Placebo Controlled Trial Of Transcranial Magnetic Stimulation In The Treatment Of Depression.
Funder
National Health and Medical Research Council
Funding Amount
$366,775.00
Summary
Depression is a severe and often disabling illness that occurs frequently in the general population. Depression is a treatable illness and the majority of patients will respond to anti-depressant medication, a form of psychotherapy or a combination of these. However, a significant percentage of patients with depression fail to respond to these therapies and currently require electroconvulsive therapy (ECT). This entails the complications and costs of multiple anaesthetics, memory impairment and ....Depression is a severe and often disabling illness that occurs frequently in the general population. Depression is a treatable illness and the majority of patients will respond to anti-depressant medication, a form of psychotherapy or a combination of these. However, a significant percentage of patients with depression fail to respond to these therapies and currently require electroconvulsive therapy (ECT). This entails the complications and costs of multiple anaesthetics, memory impairment and substantial social stigma. Transcranial magnetic stimulation is being researched as a potential alternative for these patients. It is administered to patients who are awake and alert and appears to have fewer side effects. TMS uses the unique properties of a magnetic field to produce or disrupt electrical activity in superficial areas of the brain, targeted to the areas thought to be involved in the cause of depression. Our research study will compare the two most promising types of TMS with an inactive or placebo condition. This is important to establish that the effects of TMS arise from the actual stimulation and to investigate whether one of two types of TMS administered is superior. We will administer this treatment for between 2 and 4 weeks and assess the response. We anticipate that our research will contribute to the development of TMS as a treatment methodology for this important patient group. It is crucial that a new treatment be thoroughly evaluated prior to wide dissemination of it in clinical practice. We will help define the effectiveness of this treatment and the most appropriate way in which it can be administered.Read moreRead less
The Biology Of Risk For Bipolar Disorder: Genetic Effects In A High-risk Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$856,412.00
Summary
Bipolar disorder is a severe mood disorder affecting over 350,000 Australians. Some children of bipolar disorder patients will also become ill, although currently we have no tools to predict which of these genetically at-risk young individuals will eventually develop symptoms. This study will use genetic information plus brain structural changes to predict which at-risk individuals are likely to become ill. This study will help elucidate early clinical and biological markers of bipolar disorder.
Understanding The Molecular Basis Of Bipolar Affective Disorder
Funder
National Health and Medical Research Council
Funding Amount
$812,250.00
Summary
Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define mo ....Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define more clearly the biological basis of bipolar disorder as a necessary prerequisite to improved diagnosis and treatment. The underlying causes of bipolar disorder remain unknown. However, family studies reveal the high heritability of bipolar disorder and this familial clustering provides an opportunity to use genetic approaches to identify the predisposing genes. The long-term aim of our research is to investigate the biology of those genes that either cause or predispose to bipolar disorder. We have previously reported strong evidence for a novel bipolar disorder susceptibility gene on chromosome 4, a finding which has subsequently been reproduced in several independent studies. Consequently, we hypothesise that there is a gene located on chromosome 4 that predisposes to bipolar disorder. The aim of this proposal is to identify the chromosome 4 bipolar susceptibility gene and understand how the gene causes bipolar disorder. Identifying the genes responsible for bipolar disorder will allow us to define and understand the biological basis of this severe psychiatric condition. This will ultimately lead to major improvements in the ability to diagnose, treat and prevent the illness.Read moreRead less