Kyle Williams, MD

Fellow
Child Psychiatry

Thesis Advisor

Christopher Pittenger

Thesis Project

Molecular Modeling of Childhood Neuropsychiatric Disorders: An Animal Model of Tourette Syndrome

Tourette Syndrome (TS) is a severe developmental disorder, which current estimates place at a prevalence of 6 in every 1,000 children. Tourette syndrome is characterized by both motor and phonic tics that wax and wane throughout childhood, and are known to lead to substantial morbidity. Current treatments include pharmacotherapy with neuroleptic drugs and cognitive-behavioral therapy; however, these therapies are frequently inadequate to alleviate symptoms in severe cases of TS. It is well established that the basal ganglia, and their input nucleus, the striatum, are dysfunctional in TS. Post-mortem analyses of neuronal tissue from three severe TS cases have revealed that a specific interneuronal population, the parvalbumin-positive fast-spiking interneurons (PS+FS-interneurons) may be abnormally distributed in TS patients. Our current research is aimed at understanding the role of these interneurons in the pathophysiology of TS. We are investigating novel ways of ablating this neuronal population in developmentally normal mice through combining transgenic mouse lines with an adeno-associated viral (AAV) gene delivery system. These mice will be investigated to evaluate their potential as an animal model for TS.