QBI Neuroscience Seminar: 'Convergent evidence implicates vitamin D deficiency and voltage-gated calcium channel function in schizophrenia”
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- Professor John McGrath - Queensland Brain Institute, University of Queensland, Australia, and Niels Bohr Professor, Aarhus University, Denmark
Title: 'Convergent evidence implicates vitamin D deficiency and voltage-gated calcium channel function in schizophrenia”
Abstract:
Variants in voltage-gated calcium channels (VGCCs) have been linked to risk of schizophrenia, as has prenatal vitamin D deficiency, known to be important in calcium homeostasis. In this talk I will provide a summary of recent research done in collaboration with colleagues at QBI and in Denmark that has investigated a mechanism that links these independent observations. We measured 25 hydroxyvitamin D in neonatal dried blood spots (n = 2602), and found that those in the lowest quintile of 25OHD concentration had a relative risk of schizophrenia of 1.44 (95%CI: 1.12-1.85) compared to the reference quintile. Using molecular, functional imaging and electrophysiological approaches, we demonstrate that the active form of vitamin D (1,25 dihydroxyvitamin D) induces rapid, non-genomic effects on calcium regulation in developing cortical neurons and brain.
These include increased surface expression of L-type VGCCs in primary cortical neurons, and rapid-onset enhanced calcium influx in a subset of prefrontal cortex cortical neurons. Our findings provide convergent evidence that these epidemiological and genetic risk factors may operate via shared biological pathways.
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