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
THE NATURAL HISTORY OF COGNITIVE IMPAIRMENT AND DEMENTIA IN A STROKE COHORT
Funder
National Health and Medical Research Council
Funding Amount
$290,747.00
Summary
In a current NHMRC-funded study, we have examined 200 stroke patients (and 100 control subjects) at 3 months after a stroke and one year later, and identified those who have impairment in memory and other cognitive functions. We have also studied these subjects in detail from a psychiatric perspective and performed brain scans on them using magentic resonance imaging. We find that many stroke patients have problems with their cognitive functioning which has a major impact on their lives. A large ....In a current NHMRC-funded study, we have examined 200 stroke patients (and 100 control subjects) at 3 months after a stroke and one year later, and identified those who have impairment in memory and other cognitive functions. We have also studied these subjects in detail from a psychiatric perspective and performed brain scans on them using magentic resonance imaging. We find that many stroke patients have problems with their cognitive functioning which has a major impact on their lives. A large number also become depressed. These consequences of stroke are not given sufficient importance by clinicians. The fact that stroke is a common problem in the elderly, and our society is aging, makes this a problem of major public health significance. In the new proposal, we plan to study these subjects up to 3 years with repeat neuropsychiatric assessments and brain scans to investigate the natural history of stroke-related cognitive impairment. We will determine whether further new cases of dementia develop in the period 1-3 years, what happens to the brain lesions picked up on brain scans, and how these deficiencies affect the patients' living status and their longevity. We will be able to determine the factors that lead to a good outcome, and suggest strategies that may be applicable to improve the functioning of these individuals.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 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 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.
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
An Extended Follow-up Of Stroke Patients For Cognitive Impairment And Neuropsychiatric Disorders: Sydney Stroke Study
Funder
National Health and Medical Research Council
Funding Amount
$321,800.00
Summary
Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not bee ....Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not been studied. There have been few studies of the progressive changes in MRI in patients with cerebrovascular disease. The overlap of VaD and Alzheimer's disease (AD) remains a problem for taxonomists and clinicians. One approach to the study of VaD is to examine a high risk group of subjects longitudinally to determine the early features, the risk factors and progressive changes. With this in mind, we began studying a cohort of stroke patients who are at high risk of VaD, in 1997-1999, and are following them longitudinally. The follow-up is now in its third year, and three neuropsychological assessments and two MRI-MRS scans have been performed. We propose to extend the follow-up to 5 years, with repeat neuropsychiatric, neuropsychological and MRI-MRS investigations, and wherever possible to necropsy, to determine the nature of vascular pathology that underlies cognitive impairment. Our cohort of stroke patients is arguably the most comprehensively assessed such cohorts internationally, and presents an excellent opportunity for a long-term follow-up study.Read moreRead less
Magnetic Seizure Therapy:The Neural Correlates And Neurocognitive Outcomes Of A Novel Therapeutic Approach To Depression
Funder
National Health and Medical Research Council
Funding Amount
$231,147.00
Summary
Depression is a substantial clinical problem for which ECT is the most efficacious treatment. However, ECT has cognitive side-effects which limit its applicability and acceptance by patients. The development of a new treatment with similar efficacy but which minimizes these side effects would have great clinical value. One promising possibility is magnetic seizure therapy (MST). This project will investigate the neurological outcomes of MST in depression, focusing on the cognitive outcomes.
Promotion Of Self-help Strategies For Sub-threshold Depression Via The Internet: Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$91,573.00
Summary
Depressive symptoms are common, impair individual functioning, and may develop into a full depressive disorder. Self-help for depressive symptoms is well-liked and often used, but some strategies are not as effective as others. This project will test the feasibility of promoting helpful self-help strategies to those with a high level of depressive symptoms, using the internet. The aim is to reduce the overall level of depressive symptoms and the number developing a full depressive disorder.