Understanding The Pathophysiology Of Schizophrenia, Major Depressive Disorder And Bipolar Disorder As A Basis For Improving Treatments
Funder
National Health and Medical Research Council
Funding Amount
$804,106.00
Summary
The Applicant seeks to understand the causes of the schizophrenia, bipolar disorder and major depressive disorder, which affect over 20% of the Australian population. This research is important as drug design, based on chemical remodelling, has not significantly advanced initial breakthroughs in treating psychiatric disorders and there is now a widespread belief that new drugs will only come from understand their causes.
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.
Differential Changes In Cortical Tumour Necrosis Factor Signalling In Mood Disorders And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$642,078.00
Summary
Changes in inflammation-related pathways contribute to the symptoms of psychiatric disorders and tumour necrosis factor ? (TNF) is a protein central to regulating theses pathways. We have now shown that changes in pathways regulated by TNF are present in the brains of people with schizophrenia and mood disorders. This means that the symptoms experienced by those with the different disorders may be linked to differential changes in TNF-regulated pathways in the brain.
An inability to resist a temptation or repeated failures of self-regulation can lead to 'impulsive' and 'compulsive' behaviours that relate to a host of personal and social problems (eg., excessive eating, gambling, and substance use). Despite this, very little research has studied the neural and psychological underpinnings of these behaviours. My research will take advantage of recent innovations and approaches to fill this void and have implications for diagnosis and treatment.
Is The Eye A Window To The Brain In Sanfilippo Syndrome?
Funder
National Health and Medical Research Council
Funding Amount
$852,967.00
Summary
Study of the retina and optic nerve permits evaluation of central nervous system – these structures contain both neurons and glia and are outgrowths of the developing brain. Therefore, eye examination may allow us to study the brain and monitor brain disease and the effect of therapy. This project will determine whether brain disease in a childhood-onset disorder (Sanfilippo syndrome) and treatment of it, can be monitored in this way.
Harnessing The Human Postmortem Brain To Elucidate Changes In FK506 Binding Protein (FKBP5) In The Neuropathology Of Severe Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$392,052.00
Summary
The postmortem human brain is a unique source to search for the pathological basis of severe psychiatric disorders including major depression, bipolar disorder and schizophrenia. Postmortem tissues are however being underutilised. This project will apply a selection of powerful biochemical measuring techniques to postmortem human brain tissues to uncover the molecular pathways of severe psychiatric disorders, which is knowledge that can lead to better treatments, preventions and cures.
Psychosis contributes significantly to global disease burden, affecting more than 3% of the population when schizophrenia, schizoaffective disorder, and bipolar disorders are considered together. These conditions aggregate within families, and genetic risk factors do not conform to traditional diagnostic categories. My work employs brain-based classification techniques to derive subtypes of psychosis that dissect, and/or span the diagnostic categories, for investigation of modifiable genetic and ....Psychosis contributes significantly to global disease burden, affecting more than 3% of the population when schizophrenia, schizoaffective disorder, and bipolar disorders are considered together. These conditions aggregate within families, and genetic risk factors do not conform to traditional diagnostic categories. My work employs brain-based classification techniques to derive subtypes of psychosis that dissect, and/or span the diagnostic categories, for investigation of modifiable genetic and environmental risk factors for psychosis.Read moreRead less
Pathophysiological Decision-making In Children With Obsessive-compulsive Disorder And Tic Disorders: Action-selection And Imaging Correlates
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Why is it that a person with obsessive-compulsive disorder (OCD) has trouble deciding whether or not to wash their hands? We scanned the brains of teenagers with OCD while they made decisions and found that they had difficulty using cues in their environment to direct choices. This may be an early vulnerability for the development of the disorder that could guide prevention. We plan to check if that difficulty is present in younger children with OCD and their family members.
Developing A Pathophysiological Model For Attention Deficit Hyperactivity Disorder: A Path To Biomarker Discovery
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Despite the efficacy of stimulant medication in treating attention deficit hyperactivity disorder (ADHD), we lack mechanistic accounts of the neuropathology of ADHD. A major barrier is the lack of human disease models representing clinical symptoms. The derivation of a novel, cell-based ADHD model proposed in this project will shed new light on the physiological bases of ADHD and be a rich resource for biomarker discovery
The Role Of Reelin-signalling On Cortical Neuron Migration
Funder
National Health and Medical Research Council
Funding Amount
$716,196.00
Summary
Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of d ....Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of development neurons are generated in one part of the brain and migrate great distances to a final destination. It is therefore necessary during development to have a well-orchestrated, controlled series of events that lead to the correct positioning and association of neurons. The precise functions of many gene products involved in this process are not known. One major advancement in the development of the cortex is the discovery of the protein Reelin which is found in the outermost region of the developing cortex. Mutations in Reelin, in humans, have been implicated in the causation of schizophrenia and mood disorders. These disease states are the result of altered migration of neurons in the cortex. The research proposed in this application is designed to understand the precise process of how two types of neurons migrate and assemble in the cortex. Technology today allows us to visualize, in culture, neurons as they migrate in real-time. This is referred to real time-lapse imaging and allows the researcher the ability to examine how external factors, affect migration of cortical neurons. We will determine how Reelin is involved in this process and our research will elucidate the fundamental process of cortical brain development.Read moreRead less