Emerging Severe Mental Illness In Young People: Clinical Staging, Neurobiology, Prediction & Intervention From Vulnerabi
Funder
National Health and Medical Research Council
Funding Amount
$6,229,421.00
Summary
Mental disorders, such as psychotic and severe mood disorders, are the largest cause of disability in Australia. However, there is still little known about illness onset, relapse and progression. We have developed a clinical staging model with transition points from symptomfree to subthreshold status, to threshold disorder to chronic disability. We will investigate neurobiological and psychosocial factors which increase the risk of progression through these stages and use this model as a basis f ....Mental disorders, such as psychotic and severe mood disorders, are the largest cause of disability in Australia. However, there is still little known about illness onset, relapse and progression. We have developed a clinical staging model with transition points from symptomfree to subthreshold status, to threshold disorder to chronic disability. We will investigate neurobiological and psychosocial factors which increase the risk of progression through these stages and use this model as a basis for examining the effectiveness of interventions, for example to prevent, delay or ameliorate onset and relapse, and promote vocational recovery. Thus major clinical and public health benefits and an understanding of factors that contribute to the onset and progression of illness will result.Read moreRead less
Cerebral Palsy (CP) is a devastating, common developmental brain disorder once assumed to be due to lack of oxygen at birth. Using our unique Biobank with DNA and clinical data from families with a CP child, we are examining the genetic origins of CP and how genes and risk factors in pregnancy contribute. We will use computer modelling and testing in animals and brain cells, to understand causes of CP and devise predictive, preventative and therapeutic strategies.
Delayed Radial Glial Maturation Linked To NFI Deficiency As An Underlying Cause Of Cortical Defects In Humans And Mice
Funder
National Health and Medical Research Council
Funding Amount
$801,979.00
Summary
The timely generation of neurons and glia is important for brain development and consequently brain function throughout life. Nuclear factor I (NFI) genes are important for regulating the production of neurons and glia, and people with disrupted NFI genes have severe cognitive and motor deficits. Using human genetic data and mouse models, we will analyse how disrupting these genes affects brain development, and changes the overall structure and wiring of the cerebral cortex as well as behaviour.
Clinical Genetic Phenotyping Of Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$582,114.00
Summary
Individuals with autism spectrum disorders (ASD) have difficulty with communication, social interaction and intellectual disability. The cause is generally not known although most cases have a genetic basis involving multiple genes and possibly environmental factors. We will study families of children with ASD and carefully characterize features related to ASD in family members. This will help us to understand how ASD is inherited and serve as the basis for the discovery of autism genes.
Genetic And Functional Analysis Of Brain Malformations
Funder
National Health and Medical Research Council
Funding Amount
$105,327.00
Summary
Disorders of early brain development are recognised as a significant cause of illness and disability in children. Unfortunately, the causes of these conditions are poorly understood, and treatment options are limited. It has become apparent that many of these conditions have an underlying genetic basis. This project will identify genes that regulate brain development and aid the development of improved treatment programs for brain and mind disorders.
Cellular Mechanisms Controlling Neural Crest Cell Migration Along The Developing Gut
Funder
National Health and Medical Research Council
Funding Amount
$368,895.00
Summary
Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by ne ....Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by neuron precursors takes 5 days in mice and 6 weeks in humans. Studies of the mechanisms controlling the migration of neuron precursors along the gut have provided fundamental information about cell migration in general. Genetic studies in humans and mice have identified some of the genes that are necessary for the migration of neuron precursors along the gastrointestinal tract, but for some of the key genes, their precise role is unknown. We have recently developed a method for imaging living neuron precursors migrating through explants of embryonic mouse gut. In the current proposal we will meld imaging and genetic studies to understand how mutations in particular genes lead to migration defects. In particular, how do particular mutations affect the migratory behaviour of enteric neural precursors? We have also previously shown that neuron precursors migrate along the gut in close association with axons. We will examine the nature of these interactions - in particular, who is following whom, and what happens when cell migration and axon growth are uncoupled? These studies, which will investigate a number of critical aspects of the migration of neural precursors into and along the developing gut, are central to understanding how the enteric nervous system is established along the gastrointestinal tract.Read moreRead less
Ocular Motility In Autism And Asperger S Disorder: Dissociation Of Motor Deficits.
Funder
National Health and Medical Research Council
Funding Amount
$131,235.00
Summary
We will use ocular motor technology to investigate motor dysfunction in autism and Asperger's disorder, to advance our understanding of the neurobiological bases of these disorders. This will help clarify whether neural networks are differentially disrupted in these disorders, as our previous clinical research suggests. This dissociation and the subsequent development of an ocular motor clincal screen may improve diagnosis, and potentially treatment, of these devastating conditions.
Novel Epidemiological Methods To Infer The Causal Effects Of Risk Factors On Neuropsychiatric And Cardiovascular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$182,003.00
Summary
Epidemiological studies, which associate risk factors and disease, are central in informing public health policy. Because causality is difficult to ascertain from these associations, public health interventions based on these findings are at some risk of failure. We propose to develop, extend and apply an innovative epidemiological approach, Mendelian randomization (MR) to resolve the causal relationship between risk factors and neuropsychiatric and cardiovascular disorders.
NeuroSleep: The Centre For Translational Sleep And Circadian Neurobiology
Funder
National Health and Medical Research Council
Funding Amount
$2,659,061.00
Summary
NeuroSleep, the Centre for Translational Sleep and Circadian Neurobiology, will foster innovative clinical research and translation to develop national capacity in understanding how sleep disorders and dysfunction of the body clock impact on health. The Centre will focus its activities on the two-way relationship between disrupted sleep and body clock systems and brain disorders. Our goal is to improve brain performance, workplace safety and health outcomes in patients with sleep and circadian d ....NeuroSleep, the Centre for Translational Sleep and Circadian Neurobiology, will foster innovative clinical research and translation to develop national capacity in understanding how sleep disorders and dysfunction of the body clock impact on health. The Centre will focus its activities on the two-way relationship between disrupted sleep and body clock systems and brain disorders. Our goal is to improve brain performance, workplace safety and health outcomes in patients with sleep and circadian dysfunction and in the general community.Read moreRead less