Understanding The Role Of Muscarinic Receptors In The Pathophysiology Of Depression And Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$480,074.00
Summary
The causes of bipolar disorder and major depressive disorder, which effect many Australians, remain unknown. We have recently shown decreases in muscarinic receptors in the brain of people with bipolar disorder and major depressive disorder. Muscarinic receptors are important in maintaining the functions of the brain that seem to be affected in people with bipolar disorder and major depressive disorder. Here we seek to understand how changes in muscarinic receptors occur in both disorders.
THE NEUROBIOLOGICAL BASIS OF INDIVIDUAL DIFFERENCES IN SUSCEPTIBILITY TO THE CONSEQUENCES OF STRESS
Funder
National Health and Medical Research Council
Funding Amount
$583,875.00
Summary
Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those t ....Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those that tend towards active coping strategies, such as attempting to take control of the situation. Previous studies have provided findings that suggest that passive coping is more common amongst sufferers of depression, post-traumatic stress disorder, and chronic pain syndrome than is active coping. But is this cause, or effect? And what are the intervening brain mechanisms? We attempt to address such questions in the present project using an animal model in which social conflict has been shown to trigger depression-like symptoms. In particular we wish to: (i) determine whether the patterns of brain activity triggered by social conflict are different for active vs. passive copers; (ii) determine whether the depression-like consequences of social conflict are more severe in passive than in active copers; (iii) determine whether differences in coping style and vulnerability to social conflict stress are due to the actions of a particular neurotransmitter, dopamine, in the prefrontal cortex of the brain; (iv) determine whether the actions of antidepressants might be attributable changes in prefrontal cortex dopamine function which in turn promote active coping in preference to passive coping. These studies will provide exciting new information about the neurobiological basis of individual differences in vulnerability to the harmful effects of stress, and thus will offer the hope of developing new ways of preventing devastating illnesses such as depression.Read moreRead less
Long-term Physical Exercise Improves Cognitive Performance Through Neuroimmune Modulation
Funder
National Health and Medical Research Council
Funding Amount
$493,586.00
Summary
This research investigates for how long exercise needs to carried out in order to be beneficial for cognitive function. We choose an animal model which simulates chronic brain inflammation as seen during aging processes of humans and during many inflammatory diseases affecting brain function. This research will unravel the long-term immunomodulatory and protective effects of exercise on brain function as well as the short-term anti-inflammatory effects on brain function.
Electrical Stimulation With A “Random Noise” Pattern: A New Approach For The Treatment Of Depression
Funder
National Health and Medical Research Council
Funding Amount
$523,160.00
Summary
This study is a world first, examining the use of a novel technology to treat depression by stimulating the brain mildly and non invasively. The study will examine the effectiveness of a 4-week course of Transcranial “Random Noise” Stimulation to treat depression, and will also measure whether improvement in mood is accompanied by a restoration of brain plasticity or adaptability.
Motivational drive and reward are survival processes that underpin the maintenance of homeostasis. In humans, dysregulation of these brain circuits manifests in disorders such as depression and addictions. Our projects is focused on a key subgroup of neurons in the hypothalamus that modulates reward and motivation. We aim to understand how potent reward experience (e.g. drugs) or stress modifies these circuits and to identify potential entry points for therapeutic interventions.
Defining The Role Of Inflammation In Depression During Aging
Funder
National Health and Medical Research Council
Funding Amount
$736,820.00
Summary
This proposed research investigates the bidirectional relationship between inflammation in the central nervous system (CNS) and depression during normal aging processes. It is assumed that inflammatory processes in the CNS will induce the development of depression and vice versa, that depression will lead to increased inflammation in the body. In addition, the research will study the genetic background and gene expression of inflammation contributing to both aging processes and the onset of depr ....This proposed research investigates the bidirectional relationship between inflammation in the central nervous system (CNS) and depression during normal aging processes. It is assumed that inflammatory processes in the CNS will induce the development of depression and vice versa, that depression will lead to increased inflammation in the body. In addition, the research will study the genetic background and gene expression of inflammation contributing to both aging processes and the onset of depression during aging.Read moreRead less
Transgenerational Impacts Of Paternal Stress On Offspring Mental Health: Epigenetic Mechanisms And Therapeutic Interventions
Funder
National Health and Medical Research Council
Funding Amount
$572,941.00
Summary
We are following up the extraordinary, almost ‘Lamarckian’, discovery that environmental influences on fathers can affect their offspring via ‘epigenetic’ changes to the sperm. We will explore mechanisms whereby increased levels of paternal stress can cause behavioural changes in the offspring, which are relevant to depression and anxiety disorders, and how positive environmental factors, including physical activity, may induce beneficial effects. This will have major public health implications.
Validating Novel Biomarkers Relevant To Major Depression
Funder
National Health and Medical Research Council
Funding Amount
$515,550.00
Summary
Depression prevention and treatment are public health priorities; therefore, it is critical to improve and personalise treatments, which can only be achieved by advancing knowledge of its underlying biology. This research project will contribute to validating potentially relevant genes for MDD risk or antidepressant response and to provide the scientific foundation for future strategies to test their products as MDD biomarkers in the clinical setting.
The Retina As A Chemogenetic Target For The Treatment Of Depression
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Treatments for depression are often poor because they lack selectivity. By inserting receptors that respond to an inert drug, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) can turn on-or-off very specific classes of cells, providing an exciting treatment direction for depression and other neuropsychiatric diseases. The long term goal of this project is to create a highly effective DREADD-based treatment for depression, which is activated by either eye drops or a pill.
The Orexin System: A Link Between Addiction And Depression
Funder
National Health and Medical Research Council
Funding Amount
$378,426.00
Summary
Relapse represents the most significant barrier to the successful treatment of addiction Interestingly, relapse rates are significantly higher amongst addicts with a concurrent mood disorder such as depression. This fellowship will use a number of cutting-edge techniques to explore the role of a hypothalamic peptide called 'orexin' in both relapse and depression and will thereby guide translational research aimed at developing pharmacotherapies designed to treat these disorders.