Investigating Circadian Rhythms in Youth with Persistent Tic Disorders

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Abstract   Persistent Tic Disorders (PTD), including Tourette's Disorder (TD) are neuropsychiatric conditions marked by movements and/or vocalizations present for longer than one year, and associated with impairments in quality of life. Many individuals do not significantly benefit from existing behavioral and pharmacological treatments. Enhanced knowledge of the pathophysiological mechanisms implicated in PTDs may aid identification of new targets for treatment development. Circadian rhythm disruption frequently presents in psychiatric and neurological disorders and may be implicated in PTDs. Case studies show morning exposure to light therapy, known to advance circadian phase is associated with modest to large tic reductions suggesting the presence of circadian abnormalities (i.e., phase delay) in select individuals with PTDs, which may contribute to tic symptom onset, course, and treatment response, and be linked to underlying PTD pathophysiology. Circadian phase is commonly assessed through dim light melatonin onset, as it is the most reliable marker. The strongest phase shifting agent is light therapy, which is associated with circadian phase shifts in circadian rhythm sleep disorders, mood disorders, and other psychiatric and neurological disorders. Moreover, light therapy is associated with improvements in the core psychiatric and neurological symptoms. Light therapy historically has involved administration of bright white light via a light box. However, adherence may be reduced by adverse side effects from bright light, and burden due to limited mobility and time constraints. A viable alternative is wearable short wavelength blue light therapy – shown to be more effective at phase shifting circadian rhythms at lower intensities and shorter durations relative to white light. Therefore, the present project utilizes a translational approach to identify and test a new mechanism for target engagement in PTDs. This study will assess circadian phase and phenotype in 35 youth ages 13 to 17 relative to 35 sex- and pubertal stage- matched healthy control subjects, and assess the degree to which wearable short wavelength light therapy targets this putative circadian mechanism, and is associated with improvements in tic symptoms. Drawing on the expertise of project co-mentors: Christopher Colwell, Ph.D. and John Piacentini, Ph.D.; and consultants: Meredith Coles, Ph.D., Dana McMakin, Ph.D., Helen Burgess, Ph.D., and Catherine Sugar, Ph.D. the proposed project will provide comprehensive training in circadian physiology; circadian measurement and treatment; experimental therapeutic frameworks as they pertain to pediatric psychopathology, including tic disorders and sleep; and biostatistics. Findings will enhance our understanding of the role of circadian rhythms in Persistent Tic Disorders and may provide new targets for future treatment development.