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
Defining The Function Of Two Discrete Precursor Cell Populations In The Adult Hippocampus: Potential For The Treatment Of Cognitive And Mood Disorders
Funder
National Health and Medical Research Council
Funding Amount
$578,985.00
Summary
Adult hippocampal neurogenesis plays a crucial role in fundamental cognitive processes such as learning and memory formation and mood regulation. Our laboratory has identified two discrete pools of quiescent stem and precursor cells in the adult hippocampus that can be activated by distinct mechanisms. This study will examine the functional properties of new neurons generated from these discrete pools and their role in improving behavioural outcomes associated with cognition and mood regulation
A Breakdown Of Cortical Homeostasis In Depression: A Focus On The Anterior Cingulate
Funder
National Health and Medical Research Council
Funding Amount
$625,629.00
Summary
Major depressive disorders affect 20% of the Australian population. Some symptoms of major depressive disorders arise because of a dysfunction of the human brain, particularly the cortex. Our studies show there are biochemical changes in the anterior cingulate cortex in people with mood disorders. We will now extend our studies to show there is a breakdown in the balance between neurotransmitter and neuroinflammation pathways in the anterior cingulate cortex in major depressive disorders.
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.
CRE In Traumatic Brain Injury Psychosocial Rehabilitation: Breaking Down Barriers For Social Reintegration
Funder
National Health and Medical Research Council
Funding Amount
$2,678,530.00
Summary
Severe traumatic brain injury (TBI) from motor vehicle accidents, assaults and accidents will surpass many diseases as the major cause of disability in the Western world by 2020. It causes cognitive and emotional disorders that result in unemployment, loss of relationships, social isolation and depression in adults and children. This CRE is a world first, tackling deficits in fatigue, mood, self-awareness and self-regulation and social competency, i.e. speech, social skills and communication.
Neurodevelopmental Mechanisms And Early Intervention In Psychiatric Illness
Funder
National Health and Medical Research Council
Funding Amount
$652,765.00
Summary
Schizophrenia and depression are devastating mental illnesses and a huge burden to society. Drug treatments can be beneficial, but many patients are either treatment-resistant or show severe side-effects. There is an urgent need for truly novel treatment strategies which should ideally prevent symptoms. The main aim of this project is to elucidate brain mechanisms involved in schizophrenia and depression development to inform clinical research about improved preventative treatment strategies.
Modeling Early Intervention In Schizophrenia: Role Of BDNF
Funder
National Health and Medical Research Council
Funding Amount
$467,371.00
Summary
Schizophrenia is a major burden on sufferers and society at large. Currently available treatments are only partially effective and often associated with significant side effects. This project will explore the neurobiological mechanisms of early preventative treatments in schizophrenia using a 'two hit' developmental mouse model. The results could have important clinical implcations for preventative treatment options.
Neurobiology Of Relaxin-3/RXFP3 Systems: Anatomical And Functional Studies In Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$94,242.00
Summary
Mental illness is an economic and health burden worldwide, with huge costs in medical spending, lost productivity, poor quality of life for sufferers and mortality. Relaxin-3 is a peptide that acts widely within neural circuits to modulate brain activity that is altered in conditions such as anxiety and mood/sleep disorders. Our research assessing the effect of genetic removal of relaxin-3 signaling on behaviour will add to our knowledge of brain function and improve mental health outcomes.