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
Application Of Intelligent Conducting Polymers For Treating Schizophrenia And Allied Disorders Focusing On Neuronal Outgrowth, Myelination And Synaptogenesis
Funder
National Health and Medical Research Council
Funding Amount
$698,314.00
Summary
This project involves cross-disciplinary collaboration between researchers at the forefront of materials engineering, nanotechnology, neural pathology, human stem cell biology and mental health disciplines. We will use a nanodevice to apply electrical stimuli and growth factors to improve brain function in schizophrenia and allied disorders.
RISK AND PROTECTION FACTORS FOR NORMAL AND ABNORMAL BRAIN AGEING: A LONGITUDINAL EPIDEMIOLOGICAL MRI STUDY
Funder
National Health and Medical Research Council
Funding Amount
$153,020.00
Summary
Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed u ....Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century. In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups - 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being assessed in 1999-2001, and will be followed up at 4-yearly intervals for 20 years. The focus of the study is on neuropsychiatric disorders (anxiety, depression, substance use and cognitive disorders). In this application, we propose to perform MRI scans and blood tests on a quarter (n-500) of the 60-64 sample to obtain an epidemiological sample for brain morphology. Not only will we be able to study changes in brain morphology over time, and relate it with cognitive function and psychiatric disorder, we will also be able to assess the role of risk and protection factors. We are particularly interested in brain reserve, dietary factors (anti-oxidants, omega 3, wine and folate) and drugs (anti-inflammatory drugs, hormone replacement and vitamin supplements) as protection factors, and hypertension, homocysteine levels, white matter lesions on MRI and low hippocampal volumes as risk factors for cognitive impairment and dementia. We also want to study the brain morphological correlates of Depression in a community sample. The study will enhance our understanding of the ageing brain, both in health and disease, and identify factors that increase or decrease the risk of cognitive impairment and psychiatric disorder in old age.Read moreRead less
Does Caffeine Affect The Development Of The Very Immature Brain: Dose Response Relationship?
Funder
National Health and Medical Research Council
Funding Amount
$668,386.00
Summary
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity (AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses of caffeine on the developing brain in a long-gestation species.
A Selective Prevention Trial Using Novel Pharmacotherapies In An Older Age Cohort At Risk For Depression
Funder
National Health and Medical Research Council
Funding Amount
$975,259.00
Summary
The study will examine whether omega-3 fatty acids or antidepressants prevent the onset of depression in a group of older community participants who have previously been identified as being "at risk" of depression. The study will incorporate sophisticated brain scanning methods, as well as tests of brain functioning to determine acute brain changes, reduction in cognitive decline and prevention of depression over a one-year period.
New And Improved Treatment Strategies For Neonatal Seizures
Funder
National Health and Medical Research Council
Funding Amount
$883,209.00
Summary
Around 10% of neonates in Australia are diagnosed with seizures each year. Seizures worsen neurodevelopmental outcome following hypoxic brain injury. Despite evidence of the limited effectiveness and potential neurotoxicity of current anti-seizure medication, treatment has not changed for many decades. The objective of this study is to optimise treatment of neonatal seizures with a compound that is effective and does not cause harm, or indeed provides neuroprotection for the compromised brain.
A Randomised Controlled Trial Of Low-dose Ketamine In Youth With Severe Depression And Elevated Suicide Risk
Funder
National Health and Medical Research Council
Funding Amount
$2,232,757.00
Summary
Recent research has shown that a single injection of low-dose ketamine has powerful, though short-lived, antidepressant effects. Effective treatments are urgently needed for young people with severe depression. This will be the first controlled study to test whether repeated doses of ketamine, given over 4 weeks, is effective for young patients.
The Burden Of Late Preterm Birth On Brain Development And 2 Year Outcomes – A Prospective, Longitudinal Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$838,690.00
Summary
80% of preterm babies are born from 32-36 weeks’ gestation, and are late preterm (LPT). LPT children have more learning problems, but why this occurs is unknown. This study aims to understand the effect of LPT birth on brain development. We will do brain scans at term and assess development at 2 years of age of 200 LPT and 200 full-term children. We expect LPT babies will have subtle alterations in brain development compared with term controls which will be associated with delayed development.
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
Neuroactive Steroids In The Developing Brain: Potential For Preventing Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown tha ....Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown that protective neuroactive steroids are present in very large amounts in the fetal brain. Steroids produced by the placenta are converted to these neuroactive products by enzymes in the brain leading to the high levels that are seen during fetal life. Certain adverse conditions during pregnancy as well as preterm birth may cause marked changes in the balance of steroids that could increase susceptibility to brain injury. We have found that areas of the brain, where damage most often occurs, normally contain the highest amount of protective steroids, but only in late pregnancy. This suggests that disturbances that lower steroid production in these areas could contribute to the death of cells, particularly in mid-pregnancy and after premature birth. In the proposed studies, we will examine whether a toxic balance of steroids develops following adverse events in pregnancy as well as the areas of the brain where this is most pronounced. We will examine the changes in the expression of enzymes that can potentially cause the accumulation of protective steroids in the brain. We will then examine treatments that can raise the concentration of steroids and determine which combination of steroids best reduces cell death and brain injury following complications during pregnancy. The findings of this work will indicate the best therapeutic approach that may be adopted to modify the concentration of certain steroids so as to reduce the risk of brain damage in the fetus and neonate.Read moreRead less