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Stress And HPA Axis Function In First-episode Psychosis: Relationship With Clinical Features And Dynamic Brain Changes
Funder
National Health and Medical Research Council
Funding Amount
$182,378.00
Summary
This research examines the role of stress in the progression of psychotic disorders- a group of severe mental illnesses that include schizophrenia. We will investigate whether patients with psychosis who have an abnormal response to stress experience more severe and distressing symptoms as well as brain volume changes during the initial phase of illness. The results of this research could have important implications for the development of more effective treatments for these disorders.
THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
Neuroendocrine Responses To Psychological Stress: Unmasking The Protective Role Of The Prefrontal Cortex.
Funder
National Health and Medical Research Council
Funding Amount
$346,153.00
Summary
This project seeks to build up a picture of one of the mechanisms that the brain uses to protect our bodies from the potentially harmful effects of psychological stress. When we are subjected to psychological stress one of the consequences is the release of a hormone, corticosterone, into the blood-stream. This can be beneficial in the short-term as it helps our body redistribute its pattern of energy utilization in a way that helps in coping with an unexpected challenge. However, excessive secr ....This project seeks to build up a picture of one of the mechanisms that the brain uses to protect our bodies from the potentially harmful effects of psychological stress. When we are subjected to psychological stress one of the consequences is the release of a hormone, corticosterone, into the blood-stream. This can be beneficial in the short-term as it helps our body redistribute its pattern of energy utilization in a way that helps in coping with an unexpected challenge. However, excessive secretion of corticosterone due to excessive exposure to psychological stress can damage your health. For example, it can make you more susceptible to infection and also accelerate the rate at which your brain ages. The brain possesses certain mechanisms which try to limit the release of corticosterone when you are subjected to psychological stress. Unfortunately these mechanisms are not quite up to doing the necessary job under the conditions in which we live today, i.e. a very high level of psychological stress is a common feature of modern life. Nevertheless we believe that if we can properly understand these protective mechanisms in the brain, it may be possible to develop drugs which can boost their efficiency. In the long term this could greatly reduce ill-health in our society.Read moreRead less
The Impact Of Severe Asthma During Pregnancy On Placental Function And Fetal Hypothalamic-pituitary-adrenal Function
Funder
National Health and Medical Research Council
Funding Amount
$209,242.00
Summary
This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased ....This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased intake of glucocorticoids for the treatment of asthma during pregnancy changes how the placenta functions and allows the fetus to be exposed to maternal glucocorticoids causing changes in fetal development. We will examine placental blood flow and measure some placental enzymes that may be involved in the control of blood flow in placentas collected from women with mild, moderate and severe asthma and compare them to non-asthmatic women. We will look at placental blood flow in utero using Doppler ultrasound and also in vitro after the placenta is delivered. We want to see if the fetus is affected by increased intake of glucocorticoids by the mother by measuring a hormone estriol, which originates from the fetus. We will measure estriol throughout pregnancy as it can easily be detected in the mothers' urine. These studies will tell us if glucocorticoid intake for the treatment of asthma can exert effects on the placenta and baby during pregnancy. These studies will make a significant contribution both scientifically and clinically. At a scientific level we will be able to examine how increased maternal glucocorticoid intake during pregnancy affects placental mechanisms and whether these changes affect the fetus and clinically the outcome of this study will allow us to optimize asthma therapy during pregnancy so that we can improve the outcome for the baby.Read moreRead less
Increased Vulnerability To Stress During Opiate Dependence: Molecular, Anatomical, And Behavioural Correlates
Funder
National Health and Medical Research Council
Funding Amount
$272,640.00
Summary
Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, s ....Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, stress increases the pleasurable effects of heroin and stress increases the aversive effects of heroin withdrawal. These effects will encourage addiction and discourage addicts from seeking treatment. Stress can also cause an otherwise drug-free individual to relapse to heroin addiction despite having been drug-free for some time. In this project we will study why stress has such a large impact on heroin addicts and heroin addiction. We will test the hypothesis that heroin use actually produces profound alterations in the neural network in the brain which controls responses to stress. This project uses a simple animal model of heroin addiction whereby rats are injected with morphine to study the regulation of several genes which are important in responding to stress. We will also study how this exposure and changes in gene expression alter neurobiological, cardiovascular, and behavioural responses to stress. This project will identify parts of the brain that are altered during heroin addiction, and will also identify why heroin addicts are more vulnerable to stress than the general population. Therefore, this project will help us to identify targets for therapeutic intervention (both psychological and pharmacological) and possibly disrupt the addictive cycle.Read moreRead less
Investigating A Novel Agent To Limit Brain Injury And Post-stroke Complications
Funder
National Health and Medical Research Council
Funding Amount
$412,429.00
Summary
Stroke is a leading cause of morbidity and mortality worldwide, but treatment options remain limited. The goal of this research project will be to examine the potential of new agent to protect the brain against stroke and to also treat complications that typically occur after stroke including infection and weight loss. It is anticipated that this project will ultimately lead to the development of an effective stroke therapy.
Early Life Stress, Adolescent Brain Development And Risk For Adverse Cognitive And Psychosocial Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$640,595.00
Summary
This project aims to study pre and postnatal childhood factors and examine their association with HPA-functioning, cognition, and mental health during adolescence in the Western Australian Pregnancy Cohort Study (Raine Study). Childhood exposures include not only trajectories of stressful life events, family functioning and mental health status during childhood, but also effects of intrauterine and postnatal growth patterns, and a comprehensive range of psychosocial, familial and environmental f ....This project aims to study pre and postnatal childhood factors and examine their association with HPA-functioning, cognition, and mental health during adolescence in the Western Australian Pregnancy Cohort Study (Raine Study). Childhood exposures include not only trajectories of stressful life events, family functioning and mental health status during childhood, but also effects of intrauterine and postnatal growth patterns, and a comprehensive range of psychosocial, familial and environmental factors. It is our objective to characterise functional polymorphisms for genes related to stress regulation and examine their interactions with early life exposures and their neurobiological consequences. We will also test 16 year old Raine subjects for cognitive ability, and in some we will image their brain activity while performing these tests. We anticipate to enhance the already comprehensive phenotypic Raine Study data base with neurobiological information for future neuroscience studies as the Raine cohort matures. We hypothesise that increased and sustained trajectories of early life stress, family dysfunction or poor mental health during childhood will increase the risk of Raine Study adolescents experiencing: (i) - increased stress sensitivity with higher baseline cortisol levels during adolescence; (ii) - increased adolescent stress sensitivity, if they are carriers of specific haplotypes of the glucocorticoid and mineralocorticoid receptor genes.;(iii) - depression during adolescence, if they are homozygous or heterozygous for the short allele of the serotonin transporter (5-HTT) gene; (iv) - poorer cognitive performance and increased atypical non-prefrontal cortex (PFC) brain activity during cognitive testing as measured by fMRI; and (v) -more mental health problems during adolescence.Read moreRead less
How Commonly Used Psychoactive Drugs Affect The Hypothalamo-pituitary-adrenal Axis
Funder
National Health and Medical Research Council
Funding Amount
$411,448.00
Summary
The body makes a number of responses when it is subjected to stress, and these include the secretion of hormones from the adrenal gland, including cortisol. It is not surprising that cortisol has effects upon the way the brain operates, nor is it surprising that diseases that are associated with stress (e.g. depression, alcoholism and other psychiatric complaints) create abnormal cortisol secretion. The drugs that are known to be successful in treating conditions such as depression and anxiety h ....The body makes a number of responses when it is subjected to stress, and these include the secretion of hormones from the adrenal gland, including cortisol. It is not surprising that cortisol has effects upon the way the brain operates, nor is it surprising that diseases that are associated with stress (e.g. depression, alcoholism and other psychiatric complaints) create abnormal cortisol secretion. The drugs that are known to be successful in treating conditions such as depression and anxiety have been shown to affect the secretion of cortisol, but, somewhat paradoxically, we do not precisely know how they operate. The aim of this research is to examine how drugs that are commonly used for the treatment of a number of psychiatric conditions (e.g. Prozac, Tofranil, Xanax, morphine and naltrexone) affect the secretion of hormones from the brain that ulitmately regulate the secretion of cortisol. We propose that the effects of these drugs is related to how they operate, and for how long they have been given. The findings generated by this research may help us determine new ways of diagnosing and treating a range of conditions.Read moreRead less
Epigenetic Programming Of The Hypothalmo-Pituitary-Adrenal Axis
Funder
National Health and Medical Research Council
Funding Amount
$550,951.00
Summary
It has been shown that the pattern of nutrition in early pregnancy is important in determining the subsequent health of the fetus and newborn. Interestingly, the nutritional environment of the early embryo, when nutrient demands are minimal has been shown to be important in determining the development of the capacity of the fetus to respond to stress in the womb and the timing of delivery. This proposal seeks to understand the mechanisms that underlie these responses.
Central Control Of Stress-induced Changes In Immune Function.
Funder
National Health and Medical Research Council
Funding Amount
$411,724.00
Summary
LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol ....LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol in our body is beneficial because it can prevent the infection from taking hold in our body and spreading. However if we are chronically stressed our brains tell the adrenal glands to secrete excessive amounts of cortisol over long periods of time and this imbalance can actually hinder the ability of one's immune system to fight an infection. The unfortunate consequence is that the infection is more likely to win the battle and spread to cause further havoc. The present study will identify which areas of the brain are important in driving the secretion of cortisol during infection and how long-term stress can influence those areas. Because we might be exposed to long-term psychological stress that is repeated regularly or irregularly we will determine which pattern of stress has the greatest effect. An investigation into how the brain operates during long-term stress and infection will help us develop ways to prevent stress from disrupting our immune systems.Read moreRead less