A Double-blind Controlled Trial Of RTMS In The Treatment Of Bipolar Depression
Funder
National Health and Medical Research Council
Funding Amount
$401,605.00
Summary
Bipolar affective disorder (BPAD) is a serious mental illness of substantive impact but there has been relatively sparse investigation of treatments for it. One of the only substantially new treatments developed for depression in recent years has been rTMS. Repetitive TMS has been evaluated in over 30 trials conducted, but no substantive trials have explored its use in bipolar depression. We propose to do this, conducting a large scale clinical trial.
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
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
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
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
Genetic Variations And Dopaminergic Contributions To Prefrontal Cognitive Systems In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$169,904.00
Summary
Depression and cognitive change associated with menopause frequently occur, but are poorly understood. This research will allow for a greater understanding of the nature of the relationship between menopause, depression and cognitive impairment. The exploration of the efficacy of hormonal and antidepressant treatment on both mood and cognition will contribute to a better understanding to allow for improved treatment options.
THE EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION (TMS) ON RAT MODELS OF DEPRESSION
Funder
National Health and Medical Research Council
Funding Amount
$204,274.00
Summary
Repetitive Transcranial Magnetic Stimulation (rTMS) is the direct stimulation of the brain by using high field magnetic pulses. It is a new technique that has been demonstrated to have some potential as a treatment of depressive illness and possibly other neuropsychiatric disorders. At this early stage of its investigation, the parameters of stimulation that are most likely to be therapeutic, and its mechanisms of action, are not known. Published studies vary in the frequency, duration and exten ....Repetitive Transcranial Magnetic Stimulation (rTMS) is the direct stimulation of the brain by using high field magnetic pulses. It is a new technique that has been demonstrated to have some potential as a treatment of depressive illness and possibly other neuropsychiatric disorders. At this early stage of its investigation, the parameters of stimulation that are most likely to be therapeutic, and its mechanisms of action, are not known. Published studies vary in the frequency, duration and extent of stimulation, with no firm guidelines about optimal parameters. Empirical study of the relative effects of stimulation at different frequencies, at different numbers of stimuli and for different durations is therefore important for the future development of this treatment. Such an investigation is best carried out in an animal model of depression for both ethical and practical reasons, as such studies in patients would possibly take many years and be extremely difficult to conduct. We propose such a study in rat models of depression which have demonstrated validity and utility in drug research. Rat models have a long track record in developing psychiatric treatments and are cost-effective and of proven value. We also plan to investigate the neuroanatomy of the immediate-early genes induced by TMS and compare it with electroconvulsive shock (ECS) and a tricyclic antidepressant, two established treatments of depression. The results will have implications for future human studies in guiding us toward the optimal parameters for therapeutic effects. They will also enhance our understanding of the mechanism of action of TMS in depression.Read moreRead less
A Prospective Study Of Inflammatory Cytokines As Common Factors In The Aetiology Of Both Depression And Osteoporosis.
Funder
National Health and Medical Research Council
Funding Amount
$291,230.00
Summary
Both depression and osteoporosis are common, debilitating and expensive diseases and there is research to suggest that these conditions are related. This study will examine a potential common mechanism, inflammation, which may underlie both diseases. It will focus on circulating proteins which are associated with both depression and fragility fractures, and examine the role they play in both disorders.
Delineating The Anatomical Correlates Of Neurocognitive And Psychomotor Dysfunction In Depression By FMRI
Funder
National Health and Medical Research Council
Funding Amount
$388,340.00
Summary
Severe depression is characterised by slowing of mental and motor abilities. Previous research by our group indicates the role of small frontal and basal brain regions in the regulation of these abilities. This research will extend our previous studies by providing new information detailing the underlying physiology of behavioural and structural abnormalities in patients with severe depression. Emerging research by our group and others suggest that some types of severe depression in later life a ....Severe depression is characterised by slowing of mental and motor abilities. Previous research by our group indicates the role of small frontal and basal brain regions in the regulation of these abilities. This research will extend our previous studies by providing new information detailing the underlying physiology of behavioural and structural abnormalities in patients with severe depression. Emerging research by our group and others suggest that some types of severe depression in later life are due to undetected forms of cerebrovascular disease. If we are able to demonstrate that the key features of severe depression of this type (psychomotor, attentional, memory and executive disturbance and global disability) are related to such brain changes this may lead to a major breakthrough in the prevention and treatment of these disorders. A new type of brain imaging technology called 'functional Magnetic Resonance Imaging' (fMRI) permits simultaneous investigation of the structure and function of small areas of the brain. As the technique does not use radiation and can be performed while the patient is completing mental tasks, it can be used in repeated experiments. Consequently, it permits description of brain changes (areas of activation) that occur during specific mental tasks. Therefore, if we are now able to use this technique to extend our previous clinical and imaging studies we will be able to test whether some forms of late-life depression are due to undetected brain changes.Read moreRead less
Depressive Illness And The Heart: Identifying The Relation Between Affective Disorders And Coronary Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$503,625.00
Summary
Major depression is ranked fourth among the 10 leading causes of the global burden of disease and, if epidemiological projections are correct, by 2020 it will reach second place. Patients with depression are at increased risk of developing coronary heart disease. This elevated risk is independent of conventional risk factors such as smoking, obesity, hyperlipidaemia, diabetes and hypertension. Also conclusively demonstrated is the adverse effect of depression in patients following myocardial inf ....Major depression is ranked fourth among the 10 leading causes of the global burden of disease and, if epidemiological projections are correct, by 2020 it will reach second place. Patients with depression are at increased risk of developing coronary heart disease. This elevated risk is independent of conventional risk factors such as smoking, obesity, hyperlipidaemia, diabetes and hypertension. Also conclusively demonstrated is the adverse effect of depression in patients following myocardial infarction (MI), which materially increases mortality. The mechanism of increased cardiac risk attributable to depressive illness is at present uncertain but activation of the sympathetic nervous system, exaggerated platelet reactivity and-or altered baroreflex function are likely to be of prime importance. Preliminary data from our laboratory indicates that whole body and cardiac sympathetic nervous activity and cardiac baroreflex sensitivity are modified following antidepressant therapy. Identifying the underlying neurochemical mechanisms responsible for alterations in affective behaviour, and quantifying cardiac and whole body sympathetic activity directly and indirectly, and testing whether therapeutic and behavioural interventions can influence brain neurotransmitter turnover and modify cardiac sympathetic tone, platelet reactivity, and baroreflex function in a fashion likely to reduce cardiac risk, will be an important step forward in alleviating the burden of depressive illness on the community.Read moreRead less