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.