Advanced Paternal Age: Behavioural, Neuroanatomical And Genomic Correlates In The Offspring Of Older Fathers
Funder
National Health and Medical Research Council
Funding Amount
$501,565.00
Summary
The offspring of older fathers have an increased risk of developing disorders such as autism and schizophrenia. This is thought to be due to mutations in the developing sperm. Our group has shown in a mouse model that the offspring of older fathers have changes in brain shape and in behaviour, similar to some findings in autism. In this grant we will refine this animal model and explore the brain, behavioural and genetic correlates of advanced paternal age.
Functional And Structural Imaging Of Auditory Infomation Processing Deficits In Recent-onset And Chronic Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$376,000.00
Summary
Abnormalities in the auditory system have long been suspected to be present among people who suffer from schizophrenia and other psychotic disorders, due in part to the high prevalence of auditory hallucinations amongst these patients. Over the last decade, a group of Australian researchers have identified an index of auditory information processing, recorded from scalp electrodes, that is abnormal in patients with schizophrenia, and their biological relatives. The present project will examine t ....Abnormalities in the auditory system have long been suspected to be present among people who suffer from schizophrenia and other psychotic disorders, due in part to the high prevalence of auditory hallucinations amongst these patients. Over the last decade, a group of Australian researchers have identified an index of auditory information processing, recorded from scalp electrodes, that is abnormal in patients with schizophrenia, and their biological relatives. The present project will examine the relationship between these electrophysiological findings, and a new non-invasive technique of functional brain imaging, looking at changes in blood flow, that can identify the specific brain regions that are active during auditory information processing, and link these to the sources of the scalp recorded measures. Both of these functional measures will be examined in relation to the volumes of brain tissue, measured from magnetic resonance imaging scans using new analysis tools, that enable the identification of subtle changes in brain anatomy. By examining patients who have recently developed schizophrenia, those who have suffered from the illness for longer periods of time, and their close relatives, this study will provide the opportunity to identify biological markers of increased vulnerability for the development of schizophrenia.Read moreRead less
Identifying Endophenotypes For Schizophrenia And Autism: A Support Vector Machine Learning Approach
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Schizophrenia and autism are mental health problems that often occur together. Despite this, little is known about the overlap between them and how to treat people who experience both. In this study, I will compare young adults with schizophrenia and autism using three measures of brain function. I plan to employ complex statistical analyses to better understand the similarities and differences between the disorders in order to improve diagnosis and treatment.
Neurexin And Neuroligin: A Code For Synaptic Development
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
As soon as we are born, we interpret our world through our senses, learn new information and lay down memory. These processes require molecules that connect neurons together. Mutations in genes encoding these molecules result in incorrect wiring of the brain and lead to mental disorders such as autism and schizophrenia. Using simple insect models, our project aims to unravel the fundamental mechanisms of how these molecules function in the brain and how their interaction controls behaviour.
Gene-environment Interactions And Synaptic Plasticity In The Developing And Dysfunctional Cerebral Cortex
Funder
National Health and Medical Research Council
Funding Amount
$526,026.00
Summary
The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing gene-environment interactions and mechanisms of pla ....The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing gene-environment interactions and mechanisms of plasticity in postnatal brain. Many brain disorders, including schizophrenia, autism, epilepsy, Alzheimer's and Huntington's disease, involve abnormal development or function of the cerebral cortex. Our group has recently demonstrated that onset and progression of Huntington's disease, previously considered the epitome of genetic determinism, can be modulated by environmental factors, suggesting that all brain disorders must involve gene-environment interactions. In this project we are focusing on a specific molecular pathway which processes information from the environment and induces experience-dependent changes in the structure and function of neurons in cerebral cortex. We know that the molecular pathway we are examining has been linked to schizophrenia, a disorder of brain development, and we are attempting to understand how disruption of these molecular pathways can lead to the abnormal brain development and plasticity seen in this disease. We hope to discover neurobiological mechanisms which provide integrative understanding at the level of molecules, networks of neurons, and behaviour, in mouse models of brain disorders with disruption of specific genes, receiving different types of environmental stimulation. Analysing normal mice in this project will also provide new information on mechanisms of plasticity in the healthy cerebral cortex, that may underlie higher brain functions such as learning, which occurs throughout postnatal life, and memory.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.
The Role Of The Neuronal Splicing Factor A2BP1 In Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$396,412.00
Summary
Autism spectrum disorders (ASD) are characterized by language deficits, social impairments and repetitive-restrictive behaviors. ASD is one of the most highly heritable neuropsychiatric conditions, and at the same time genetically very heterogeneous. We have recently shown that shared gene expression abnormalities can be identified in postmortem brain from ASD patients. We now propose to investigate the mechanisms and functional consequences of gene expression abnormalities in ASD.
Social Functioning And Autism Spectrum Disorder In Children With Neurofibromatosis Type 1: A Multimodal Study.
Funder
National Health and Medical Research Council
Funding Amount
$107,204.00
Summary
Social difficulties and symptoms of autism spectrum disorder (ASD) are frequently found in children with neurofibromatosis type 1 (NF1), a common genetic condition. The current study will examine (1) prevalence and characteristics of ASD and social impairment in children with NF1, (2) cognitive factors contributing to ASD symptoms and (3) associated compromise to brain structure. Findings are expected to guide development of treatments to improve social functioning in children with NF1.
Outcome Prediction, Stratification And Novel Treatments In Individuals At Ultra High Risk Of Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
The Ultra High Risk (UHR) criteria have been developed to identify people at high risk of psychotic disorders such as schizophrenia so that treatments can be provided early to reduce risk and disability. However the some UHR people are at risk of other difficulties and disorders and others are not at risk of all. We need to improve our ability to distinguish between these groups so that treatment can be tailored according to risk, and develop new treatments that target underlying problems.
Pathogenesis And Therapeutic Modulation Of Aggressive Behaviour In A Mouse Model Of Autism Spectrum Disorder
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
This project focuses on understanding the causes of aggressive behaviour in mice that have a human gene mutation found in autism. Aggressive behaviour is common in autism patients and can have severe consequences on education and employment opportunities. These mice also show excess dampening of brain function (inhibition). This project will test if aggression in these mice is caused by altered inhibition.