PROJECT SUMMARY/ABSTRACTThe ability to promote and support remyelination has wide-ranging implications for a number ofneuropsychiatric conditions from multiple sclerosis to major depression. Pre-clinical evidence hasdemonstrated that thyroid hormone treatment, in the form of triiodothyronine (T3) or tetraiodothyronine (T4),can promote and support remyelination by increasing myelin basic protein mRNA and protein, oligodendrocyteproliferation and maturation, and fractional anisotropy (a diffusion imaging measure of white matter integrity).Pilot data from our own studies suggest that baseline thyroid status is correlated with the integrity of whitematter tracts associated with major depression. To date, the impact of thyroid hormone administration on whitematter tracts has not been studied in vivo in adult humans. The purpose of the proposed pilot study is toexamine changes in white matter tract integrity using high angular diffusion imaging and multi-componentrelaxometry in a population of subjects clinically indicated to receive thyroid hormone for hypothyroidism. Wewill scan patients with hypothyroidism at the initiation of treatment and at three and six months after startingthyroid hormone treatment. We will also administer scales assessing mood and cognition which have beenshown to correlate with white matter integrity. We hypothesize that thyroid hormone treatment will beassociated with an increase in fractional anisotropy, a decrease in radial diffusivity, and an increase in themyelin water fraction (markers of improved myelination) that will correlate with improvements in cognition andmood ratings. If successful, this will be the first demonstration of improved white matter integrity with thyroidhormone replacement and pave the way for therapies designed to restore structural brain connectivity.
|Effective start/end date||8/1/16 → 7/31/18|
- National Institutes of Health: $239,850.00
Myelin Basic Protein