The role of prenatal and neonatal testosterone in early brain development
University of North Carolina
Autism occurs significantly more often in males than in females, yet research on potential causes of the biased sex ratio is extremely limited. Multiple clues suggest that alterations in testosterone levels during development may contribute to this sex difference. However, there is a currently a major gap in research relevant to this hypothesis: no studies have directly examined whether testosterone is related to individual differences in brain development in human beings. The proposed study will fill this crucial gap by measuring early testosterone levels early in development using both salivary testosterone and the length of the fingers from 2 weeks to 2 years of life. These findings will be related to structural brain development assessed via high-resolution MRI on a 3T magnet at 2 weeks after birth, with follow-up scans and comprehensive neurocognitive assessments at 1 and 2 yr. Finally, in order examine a genetic predisposition for changes in testosterone level, the number of CAG triplets in the androgen receptor gene will also be assessed. Significance: Despite compelling evidence that testosterone plays a major role in brain development in animal models, almost nothing is know about its affect on brain development in humans. The proposed study will fill this crucial gap in our present knowledge by measuring early testosterone exposure and receptor sensitivity in a large population sample and relating them to development of regions known to be sexually dimorphic in childhood: the cerebrum, amygdala, hippocampus, and caudate. The resulting data is essential to critically evaluate the testosterone hypothesis of autism.