? Thyroid disease is estimated to affect 13 million Americans. The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are critical for the development of the brain, and altered T3 and T4 status can cause a variety of neuropsychological symptoms, including impaired attention. The majority of patients with the rare genetic syndrome Resistance to Thyroid Hormone (RTH) meet the diagnostic criteria for Attention Deficit-Hyperactivity Disorder. RTH is caused by a dominant negative mutation in the thyroid receptor beta (TRbeta) gene and is characterized by elevated concentrations of T3 and T4 in the presence of inappropriately normal or elevated concentrations of thyroid stimulating hormone. The TRbetaPV knock-in mice have elevated concentrations of T3 and T4 and inappropriately elevated concentrations of TSH. In addition, the TRbetaPV knock-in mice are hyperactive, show a deficit on a measure of sustained attention, and have a paradoxical response to methylphenidate (MPH) on the same test. The impaired attention and abnormal response to MPH suggest changes in the catecholaminergic systems. The goal of this proposal is to test the hypothesis that the TRbetaPV knock-in mice have alterations in the catecholaminergic systems. ? ?
