Developmental Vitamin D Deficiency And Prefrontal Cortical Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$355,570.00
Summary
The cause of schizophrenia is unknown but is believed to be due to abnormal brain development. Dopamine abnormalities are central to schizophrenia. We have developed a model of maternal vitamin D deficiency in rats, based on disease epidemiology that shows individuals that have low levels of vitamin D at birth have an increased risk of developing schizophrenia later in life. We now also show dopamine systems in regions associated with cognition may develop abnormally in our animal model.
The Developmental Vitamin D-deficiency Animal Model Of Schizophrenia:- Critical Window For Intervention And Optimal Dose
Funder
National Health and Medical Research Council
Funding Amount
$365,811.00
Summary
We have established that low levels of vitamin D at birth increase the risk of children developing schizophrenia in later life. Our studies indicate this risk is dose-dependent and may be enhanced if developmental vitamin D (DVD) deficiency is extended into postnatal life implying there may be an early critical vitamin D threshold and a critical window of exposure required to avert schizophrenia. This project will examine this and the effects of supplements using our DVD-deficiency animal model.
Maternal Vitamin D Supplementation In A Maternal Immune Activation Model Of Schizophrenia: Mechanisms Of Prevention
Funder
National Health and Medical Research Council
Funding Amount
$523,364.00
Summary
Maternal infection and vitamin D deficiency during pregnancy increase the risk of children developing schizophrenia. We model these risk factors in pregnant mice. Offspring produce schizophrenia-like behaviours. When pregnant mice with experimental inflammation are treated with the hormonally active form of vitamin D this completely abolished all schizophrenia-like behaviours in offspring. We want to a) understand this mechanism, b) replicate using a form of vitamin D safe-to-use in humans.
Multiple Sclerosis (MS) is an autoimmune disease often diagnosed in early adulthood. Outcomes very enormously, from mild to disabling. This fellowship supports research to improve outcome prediction using genetics and to examine different strategies to optimise treatment outcomes and safety. The main data source is MSBase, which tracks over 31000 people with MS globally and is based in the University of Melbourne's brain Centre at the Royal Melbourne Hospital.
Early Pharmacological Intervention In An Animal Model Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$438,857.00
Summary
The symptoms of schizophrenia do not appear until late adolescence/early adulthood. Some adolescents may be at “high risk” of progressing to clinical psychosis. There is now intense interest in using antipsychotic drugs (APDs) to delay symptoms in these patients. APD use in adolescents however is controversial. This project seeks to clarify the structural, neurochemical and functional implications of APD use in a well described animal model of schizophrenia, developmental vitamin D deficiency.
Do The Developmental Vitamin D-deficiency And Maternal Immune Activation Animal Models Of Schizophrenia Have Convergent Early Pathways ?
Funder
National Health and Medical Research Council
Funding Amount
$669,580.00
Summary
The etiology of schizophrenia is unknown but it is generally considered to have a neurodevelopmental basis and involve altered dopamine signaling. Using two distinct developmental animal models of schizophrenia we have shown convergent gestational abnormalities in how dopamine systems develop. This is possibly a convergent early etiological mechanism in schizophrenia.
Developmental Vitamin D-deficiency And Autism; Exploration Of Potential Mechanisms And Refining Phenotype In An Animal Model
Funder
National Health and Medical Research Council
Funding Amount
$442,249.00
Summary
We have now shown in a large cross-sectional study that low levels of vitamin D during gestation increase the incidence of autism in children. When we model this risk-relationship in animals we show changes in important developmental processes and behaviours previously linked to autism in children. We now want to understand both the exact downstream molecular pathways affected in the developing brain along with the precise brain structural and behavioural abnormalities produced in offspring.
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