DEVELOPMENTAL NEUROBIOLOGY PROJECT DESCRIPTIONS

Is Developmental Vitamin D deficiency a risk factor for Schizophrenia and Autism?

NHMRC funding in 2007-2008 allowed us to become the first researchers to make the connection between low maternal vitamin D and schizophrenia in offspring in later life. This clinical research continues throughout 2012 -2013 in a much larger patient cohort funded by an NHMRC Project Grant.

We have just broken the codes on our Danish sample cohort and have replicated our earlier data. This study represents a four-fold increase in cohort size. This clearly establishes that very low levels of vitamin D during pregnancy is a risk-modifying factor for schizophrenia. Another replication will be conducted using Scottish samples. These studies and the technology we have developed have led to a number of national and international collaborations also investigating neonatal levels of vitamin D and risk of autism in offspring

Does Developmental Vitamin D deficiency impair cognition in adult offspring?

We are also interested in understanding how a known risk factor for schizophrenia “Maternal Vitamin D Deficiency” changes brain function and ultimately behaviour. Impairments in cognition remain the most debilitating and least treatable symptom within this disease. An ongoing NHMRC Project Grant allows us to dissect the exact neural pathways involved in cognitive impairments.

To date we have shown that maternal vitamin D deficiency leads to impaired behaviour in adult offspring on tasks that assess attention and vigilance, which are analagous to human continuous performance studies. These results may provide specific targets to further investigate the influence of low pre-natal vitamin D on brain function. This work is leading to the development and validation of novel cognitive tasks to explore cognition in laboratory animals.

Does prenatal vitamin D deficiency lead to altered brain function in adulthood?

We have amassed considerable data to indicate that prenatal vitamin D deficiency may also change the way the brain functions in adulthood, in particular an area of the brain called the prefrontal cortex. An ongoing NHMRC Project Grant allows us to dissect the exact neural pathways altered by vitamin D deficiency during embryogenesis.

To date we have discovered a link between dopamine release in the prefrontal cortex and sensitivity to NMDA antagonists. This work may help unravel crucial neural pathways in schizophrenia.

How does Foetal Alcohol syndrome lead to impaired brain function?

Exposure to environmental insults during pregnancy can harm a developing foetus and have life-long effects on health and well-being. A well-known example is foetal alcohol syndrome (FAS) which is associated with excessive maternal alcohol consumption during pregnancy. We are now using an animal model of foetal alcohol syndrome to explore the epigenetic mechanisms that may lead to impaired brain function in the offspring. We are exploring the hypothesis that alcohol exposure in utero compromises epigenetic silencing leading to genetic and transcriptional variation in the brain and ultimately altered behaviour in adulthood. This work is an ongoing collaboration with Dr Suyinn Chong at the Mater Medical Research Institute.

Does adult vitamin D deficiency lead to altered brain function?

Animal experiments have demonstrated that a wide range of prenatal exposures, including low vitamin D levels, can impact on the behaviour of the offspring. We have now shown that low vitamin D levels during adulthood has an impact on behaviour and brain neurochemistry in rodents. These results provide the first evidence in mice to show that adult vitamin D deficiency impacts on neurotransmitter systems that are affected in a number of neuropsychiatric conditions, including autism, schizophrenia and depression. Development of this animal model will provide a platform for future investigations into the effects of vitamin D deficiency on the adult brain.

Developmental Vitamin D deficiency induces impairments in Dopamine signalling; What are the mechanisms behind this?

Dysfunction in dopamine signaling remains the cornerstone of all therapeutic approaches to treating schizophrenia. We have discovered that maternal vitamin D deficiency alters the way dopamine neurons develop. This exciting finding may bring together two of the most important hypotheses in schizophrenia, namely the “dopamine hypothesis” and the “neurodevelopmental hypothesis.”

We continue to explore this risk in the DVD-deficiency model but are now broadening our approach to incorporate other developmental animal models for this disease such as maternal infection. It is hoped such an approach will lead to uncovering convergent pathways in many disparate risk factors for this disease.

Can early intervention with antipsychotic drugs avert the onset of phenotypes important to schizophrenia in animal models?

We are intensely interested in early intervention to prevent schizophrenia. The neurobiological basis for such treatment strategies however is sadly lacking. We have received NHMRC funding to investigate both the therapeutic and adverse effects of early Intervention strategies in preventing schizophrenia like phenotypes in animal models..