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
Longitudinal Brain Changes In First-episode Psychosis: A 10 Year Follow-up MRI Study
Funder
National Health and Medical Research Council
Funding Amount
$165,250.00
Summary
It is now widely accepted that schizophrenia is associated with changes in the structure of the brain. Until recently these structural changes were considered to predate the onset of illness and to remain static. However, our own work has suggested an alternative model, which relates schizophrenia to brain changes at specific life stages. In order to demonstrate this, we intend to acquire repeat brain images on 100 patients who were initially scanned 10 years ago at the start of their psychotic ....It is now widely accepted that schizophrenia is associated with changes in the structure of the brain. Until recently these structural changes were considered to predate the onset of illness and to remain static. However, our own work has suggested an alternative model, which relates schizophrenia to brain changes at specific life stages. In order to demonstrate this, we intend to acquire repeat brain images on 100 patients who were initially scanned 10 years ago at the start of their psychotic illness. This would be the largest follow-up study of first episode psychosis in the world, with the longest interval between the first and second brain scan. Further, for a proportion of patients we will have 3 MRI scans, at illness onset, 2-4 years post-onset, followed by a third scan at 10 years, thereby providing unique follow-up brain imaging data. Based on our own and other research, we intend to explore the relationship between progressive brain change over a ten year period and: (i) the diagnosis of the patient (schizophrenia or other disorder), (ii) the clinical and functional outcome of the patient (still chronically ill or with no further episode of psychosis), and (iii) the cognitive state of the patient (their ability to perform well on tests of memory, planning and so on). We are able to conduct this study because of the existence of an infrastructure developed to follow-up patients, with a recontact rate of 70% of those patients admitted in 1992 and 1993. In this study we seek to implement these strategies for the patients identified after 1994. The results of this study will test our ideas derived from our model of the major psychotic illnesses and may identify the structural brain changes which are associated with the development of chronic schizophrenia and other psychoses. A further novel outcome will be the inclusion of patients who have remained well and identiifying the structural correlates of a good prognosis.Read moreRead less
Developmental Influences On Brain Structure And Connectivity: Implications For Emerging Borderline Personality Disorder
Funder
National Health and Medical Research Council
Funding Amount
$147,611.00
Summary
Borderline personality disorder (BPD) is a severe, debilitating mental illness that has usual onset in adolescence. Research has highlighted the importance of adolescent brain development, particularly the maturation of brain connections, in onset of mental illness. Brain mapping techniques will be applied to gain a better understanding of BPD onset and progression within an approach that integrates neurobiology and psychosocial context. This is critical for understanding development of BPD.
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
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
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
Clinical Correlates Of The Wish To Hasten Death Among The Terminally Ill
Funder
National Health and Medical Research Council
Funding Amount
$131,360.00
Summary
There is little research that has directly examined the role of the health professional in a patient's wish to die and the implications of this for the support and development of services to provide care to a dying patient. The aim of this study is to examine factors in the health service, clinical care and social environment that influence the wish to hasten death among terminally ill patients. This is an issue of increasing importance in our community as legislative change is undertaken to ena ....There is little research that has directly examined the role of the health professional in a patient's wish to die and the implications of this for the support and development of services to provide care to a dying patient. The aim of this study is to examine factors in the health service, clinical care and social environment that influence the wish to hasten death among terminally ill patients. This is an issue of increasing importance in our community as legislative change is undertaken to enable assisted suicide in the terminally ill. In particular, there is very limited published research on these issues which have accessed a subject pool of patients who are based in services that specifically provide care for the terminally ill. A specific focus of this study is to examine the factors within the doctor-patient relationship that may influence a patient's wish to hasten death. The doctor's experience of subjective burden in caring for a dying patient, level of confidence in patient management and features of the doctor-patient relationhip will be assessed. This will essentially be an exploratory study which will attempt to establish methodologies that will help to increase an understanding of why some patients request euthanasia, thus leading to the establishment of sound management strategies, as well as contribute empirical data to the euthanasia debate.Read moreRead less
Intervention For Tobacco Dependence Among People With A Psychotic Illness
Funder
National Health and Medical Research Council
Funding Amount
$387,625.00
Summary
The prevalence of smoking among people with a psychiatric illness, especially schizophrenia, is greater than that in the general population. Exposure to tobacco smoke has been identified as a cause of 32 different diseases as well as a cause of fire injuries. Tobacco smoke is known to contain carcinogens, as well as nicotine and numerous other poisonous substances. An extensive body of scientific evidence shows that active cigarette smoking increases the risk of many different cancers. Smoking r ....The prevalence of smoking among people with a psychiatric illness, especially schizophrenia, is greater than that in the general population. Exposure to tobacco smoke has been identified as a cause of 32 different diseases as well as a cause of fire injuries. Tobacco smoke is known to contain carcinogens, as well as nicotine and numerous other poisonous substances. An extensive body of scientific evidence shows that active cigarette smoking increases the risk of many different cancers. Smoking related diseases rate second in frequency to suicide as the greatest contributor to early mortality in schizophrenia. Popular opinion holds that people with mental illness are lacking in motivation to change their behaviour due to the effects of their mental illness. However, a recent survey of inpatients in a psychiatric hospital in Newcastle, NSW, revealed that over a quarter of smokers were either preparing to quit or cut down on their smoking or already had taken action to reduce their smoking. The present research proposal represents the first large randomised controlled trial of an intervention for tobacco dependence among people with a mental illness. This project will compare the effectiveness of nicotine replacement therapy combined with counselling with a self-help booklet on smoking. The proposed research follows a small clinical study of the feasibility of the intervention and a small randomised controlled trial supported by the Australian Rotary Health Research Fund. The proposed study brings together the expertise of several people across Australia who have experience in treating people with mental illness and drug dependence, including tobacco dependence. The results will inform future clinical interventions for smokers with a mental illness.Read moreRead less