Sleep Disturbance in Tourette's Disorder: Potential Underlying Mechanisms.

Purpose of Review: Sleep disturbance is common in TD. However, our understanding of the pathophysiological mechanisms involved is preliminary. This review summarizes findings from neuroimaging, genetic, and animal studies to elucidate potential underlying mechanisms of sleep disruption in TD.
Recent Findings: Preliminary neuroimaging research indicates increased activity in the premotor cortex, and decreased activity in the prefrontal cortex is associated with NREM sleep in TD. Striatal dopamine exhibits a circadian rhythm; and is influenced by the suprachiasmatic nucleus via multiple molecular mechanisms. Conversely, dopamine receptors regulate circadian function and striatal expression of circadian genes. The association of TD with restless legs syndrome and periodic limb movements indicates shared pathophysiology, including iron deficiency, and variants in the BTDB9 gene. A mutations in the L-Histidine Decarboxylase gene in TD, suggests the involvement of the histaminergic system, implicated in arousal, in TD.
Summary: These biological markers have implications for application of novel, targeted interventions, including noninvasive neuromodulation, iron supplementation, histamine receptor antagonists, and circadian-based therapies for tic symptoms and/or sleep and circadian rhythms in TD.
Competing Interests: Dr. Ricketts reports grants from the Tourette Association of America, National Institute of Mental Health, and Brain and Behavior Research Foundation, relevant to the submitted work. She also reports grants and personal fees from the Tourette Association of America, grants from National Heart, Lung, and Blood Institute: Programs to Increase Diversity among Individuals in Health-Related Research; personal fees from Centers for Disease Control and Prevention, personal fees from Springer Nature, and service on the Tourette Association of America Diversity Committee, outside the submitted work. Ms. Swisher, Dr. Greene, and Dr. Silverman have nothing to disclose. Dr. Nofzinger reports being the Founder, Inventor, and Chief Medical Office of Ebb Therapeutics (formerly known as Cerêve, Inc.), a company that manufactured devices to administer frontal cerebral thermal therapy for insomnia, relevant to the submitted work and outside the submitted work. In addition, Dr. Nofzinger has multiple patents related to the frontal cerebral thermal therapy device, with royalties received on University of Pittsburgh license to Ebb Therapeutics. Dr. Colwell reports unpaid consulting for RealSleep™, outside the submitted work.