Ricketts Emily J, Swisher Valerie, Greene Deanna J, Silverman Daniel, Nofzinger Eric A, Colwell Christopher S
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Department of Cognitive Science, University of California, San Diego.
Curr Sleep Med Rep. 2023 Mar;9(1):10-22. doi: 10.1007/s40675-022-00242-5. Epub 2023 Jan 23.
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.
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 gene. A mutations in the gene in TD, suggests the involvement of the histaminergic system, implicated in arousal, in TD.
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.
睡眠障碍在抽动秽语综合征(TD)中很常见。然而,我们对其中涉及的病理生理机制的理解尚处于初步阶段。本综述总结了神经影像学、遗传学和动物研究的结果,以阐明TD中睡眠中断的潜在机制。
初步的神经影像学研究表明,TD患者运动前皮质活动增加,前额叶皮质活动减少与非快速眼动睡眠有关。纹状体多巴胺呈现昼夜节律;并通过多种分子机制受视交叉上核影响。相反,多巴胺受体调节昼夜节律功能和昼夜节律基因的纹状体表达。TD与不宁腿综合征和周期性肢体运动的关联表明存在共同的病理生理学,包括缺铁以及该基因的变异。TD中该基因突变表明组胺能系统参与其中,而组胺能系统与觉醒有关。
这些生物学标志物对新型靶向干预措施的应用具有启示意义,包括非侵入性神经调节、铁补充、组胺受体拮抗剂以及针对TD中的抽动症状和/或睡眠及昼夜节律的基于昼夜节律的疗法。