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Prevalence report by the Australian Advisory Board on Autism Spectrum Disorders (ASD) estimated that 1 child in every 160 children in the 6-12 year-old age group is affected by ASD. There is no cure for ASD and the causes are not understood. We propose that sex hormones may play a role in the development of these disorders. We will test this hypothesis using knockout and transgenic mouse models which have social interaction deficits and brain structure reminiscent of these disorders.
FETAL ORIGIN OF ADULT DISEASE? A POPULATION-BASED STUDY OF THE OFFSPRING OF WOMEN WITH SEVERE MENTAL DISORDERS
Funder
National Health and Medical Research Council
Funding Amount
$442,875.00
Summary
Fetal origin of adult disease is a currently influential paradigm in epidemiological research into common diseases (ischaemic heart disease, hypertension, diabetes) and behaviour problems (suicide, criminal offending). It postulates an early pathophysiological programming of outcomes that become manifest in adult life. In the proposed research we aim to examine key aspects of this model by conducting a population-based study on the developmental outcomes, antecedent and concomitant risk factors, ....Fetal origin of adult disease is a currently influential paradigm in epidemiological research into common diseases (ischaemic heart disease, hypertension, diabetes) and behaviour problems (suicide, criminal offending). It postulates an early pathophysiological programming of outcomes that become manifest in adult life. In the proposed research we aim to examine key aspects of this model by conducting a population-based study on the developmental outcomes, antecedent and concomitant risk factors, and a spectrum of neuropsychiatric morbidity in all children (N-5150) born in Western Australia in 1980-2001 to women diagnosed with schizophrenia, bipolar affective disorder or unipolar depression, as compared to children (N-504,553) born to women without a diagnosed psychiatric illness. The study will be based on record linkage, utilising the unique resource of multiple, comprehensive population databases in Western Australia. Specifically, this research will identify the range of developmental outcomes and morbidity in four consecutive birth cohorts (1980-84; 1985-89; 1990-94; and 1995-2001) of children at high genetic and environmental risk and examine their relationship to specific risk factors, including familial genetic load, obstetric complications, severity of maternal illness, and psychosocial adversity. The study will be the first of its kind and its findings will inform aetiological research into the major mental disorders, as well as clinical and public health practice. It will provide novel data on fundamental issues, such as the interaction between genetic risk and environmental factors in the causation of schizophrenia, as well as on the extent to which the risk of developing severe mental illness is immutably embedded in its fetal origin, or is modifiable by subsequent mitigating factors and appropriate intervention.Read moreRead less
A Brain-Based Measure Of Anxiety Sensitivity: Validation Of A Novel Intermediate Phenotype With Psychophysiologically-Informed Neuroimaging
Funder
National Health and Medical Research Council
Funding Amount
$271,930.00
Summary
Excessive anxiety is disabling, such that people who suffer from a clinical anxiety disorder are often crippled by overwhelming emotional and physical symptoms. We will use sophisticated brain imaging technology to understand how certain brain areas produce feelings of anxiety, including a common fear of arousal related bodily sensations. This work is expected to enhance our basic understanding of the brain basis of anxiety symptoms and may inform new treatment options with biological rationale.
Epigenetic Mechanisms Of Brain Dysfunction In Psychotic And Mood Disorders
Funder
National Health and Medical Research Council
Funding Amount
$617,836.00
Summary
This project investigates the role of epigenetic processes (i.e., functional changes to the genome affecting gene expression) in mediating the long-term effects of childhood trauma in schizophrenia and bipolar-I disorder. We specifically aim to distinguish the effects of trauma-related epigenetic effects on brain structure and function, and on the immune and stress-response systems, and the potential moderation of these effects by structural genetic variants associated with psychosis risk.
The Developmental Vitamin D Model (DVD) As An Animal Model For Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$258,075.00
Summary
Most Australians have the opportunity to enjoy the natural benefits of sunlight, however many Australians lack vitamin D. We have shown that even in Queensland, the so-called Sunshine State, vitamin D levels in the middle of winter are below World Health Organisation recommended levels. We are exploring low maternal vitamin D as a biological explanation for the universal phenomena worldwide of a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year. ....Most Australians have the opportunity to enjoy the natural benefits of sunlight, however many Australians lack vitamin D. We have shown that even in Queensland, the so-called Sunshine State, vitamin D levels in the middle of winter are below World Health Organisation recommended levels. We are exploring low maternal vitamin D as a biological explanation for the universal phenomena worldwide of a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year. Schizophrenia is a developmental disease that presents in adolescence and affects about 1% of the world's population. To date we have shown increased amounts of schizophrenia in offspring from mothers that had low blood vitamin D levels during pregnancy or who had inadequate vitamin D intake. Early signs therefore appear promising but obviously more research is required to confirm this idea. Our studies in animals have revealed that by restricting vitamin D intake in pregnant rats, newborns have brains that develop differently. Most notably lateral ventricle volume is increased, a key anatomical finding in patients with schizophrenia. When these animals become adults the increase in lateral ventricles persists. Also when we explore the behaviour of these animals we find a deficit in learning and memory similar to that seen in many schizophrenic patients. Furthermore when we expose these animals to agents that induce psychosis or agents that block psychosis in patients we see a heightened sensitivity in animals that were deprived of this vitamin in utero particularly in locomotion. These behavioural findings are consistent with the best animal models for schizophrenia. At a mechanistic level they indicate an abnormality in the two major neurotransmitters in the brain that have been consistently linked with this disease, dopamine and glutamate. The experiments outlined in this application will attempt to establish the neurochemical basis for these altered behaviours.Read moreRead less
Motor Functioning In Autism And Asperger's Disorder: Furthering Current Neurobehavioural And Clinical Definitions
Funder
National Health and Medical Research Council
Funding Amount
$354,932.00
Summary
While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isol ....While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isolated and rejected from the peer group. Also, hand writing problems have a significant impact on children's academic performance. Our previous research has suggested that there may be particular patterns of motor problems that characterise individuals with autism and Asperger's disorder. Our proposed research aims to use the kinds of 3D motion analysis technology used in the movie industry to capture exactly how people affected by these conditions move and respond to the environment. This study will enable us to highlight particular parts of the brain-motor circuitry that are affected by these disorders and will also enable us to more clearly distinguish how autism is different from Asperger's disorder. Ultimately, it is hoped that our motor investigations will lead to improved assessment and interventions for these disorders.Read moreRead less
Improving Clinical Diagnosis Of Mild Neurocogntive Disorders Using Neuropsychological Assessment
Funder
National Health and Medical Research Council
Funding Amount
$155,932.00
Summary
A major proportion of neuropsychiatric disability in old age is due to dementia or milder cognitive disorders. However, these disorders can be challenging to diagnose because of the subtlety of cognitive deficits and a lack of appropriate normative reference groups. By developing comprehensive, representative Australian normative data for key diagnostic measures and refining clinical diagnostic methods, the study will have a major impact on the accuracy of neuropsychological assessment practice.
Mood and anxiety disorders represent a tremendous cause of disability and morbidity. This research will use cutting-edge brain imaging technologies to understand why these disorders typically emerge in young people and whether brain imaging can reliably predict the effectiveness of different treatments for individual patients.
Personalised Brain Stimulation For Treatment Of Obsessive-Compulsive Disorder
Funder
National Health and Medical Research Council
Funding Amount
$666,128.00
Summary
Obsessive-Compulsive Disorder (OCD) affects more than 230,000 Australians, 25% of whom attempt suicide. This project will use a novel method to profile people with OCD based on patterns of brain activity and symptoms, and assess if such profiling can improve the efficacy of brain stimulation interventions for OCD. Results from this study will provide evidence supporting the use of personalised brain stimulation as a viable therapy for OCD.
Cognitive Control And Brain Connectivity Disturbances In Schizophrenia And Obsessive-compulsive: Clarifying Their Nature, Specificity, And Consequences
Funder
National Health and Medical Research Council
Funding Amount
$498,337.00
Summary
Deficits of behavioural control are chronic and debilitating features of both schizophrenia and OCD. As behavioural control depends on activity within many key regions of the brain, these deficits may result not only from dysfunction within one or more region, but also from abnormal interactions between them. By studying how the activity in one region depends on another, and comparing findings between disorders, a better understanding of brain function in schizophrenia and OCD can be established