Laboratory of Neuroscience, VA Boston Healthcare System and Harvard Medical School, Dept. of Psychiatry, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
Mental Health Service, VA Boston Healthcare System, West Roxbury, MA, 02312, USA; Departments of Psychiatry and Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA.
Brain Res Bull. 2022 Jul;185:140-161. doi: 10.1016/j.brainresbull.2022.05.002. Epub 2022 May 10.
Sleep disorders are widespread in society and are prevalent in military personnel and in Veterans. Disturbances of sleep and arousal mechanisms are common in neuropsychiatric disorders such as schizophrenia, post-traumatic stress disorder, anxiety and affective disorders, traumatic brain injury, dementia, and substance use disorders. Sleep disturbances exacerbate suicidal ideation, a major concern for Veterans and in the general population. These disturbances impair quality of life, affect interpersonal relationships, reduce work productivity, exacerbate clinical features of other disorders, and impair recovery. Thus, approaches to improve sleep and modulate arousal are needed. Basic science research on the brain circuitry controlling sleep and arousal led to the recent approval of new drugs targeting the orexin/hypocretin and histamine systems, complementing existing drugs which affect GABA receptors and monoaminergic systems. Non-invasive brain stimulation techniques to modulate sleep and arousal are safe and show potential but require further development to be widely applicable. Invasive viral vector and deep brain stimulation approaches are also in their infancy but may be used to modulate sleep and arousal in severe neurological and psychiatric conditions. Behavioral, pharmacological, non-invasive brain stimulation and cell-specific invasive approaches covered here suggest the potential to selectively influence arousal, sleep initiation, sleep maintenance or sleep-stage specific phenomena such as sleep spindles or slow wave activity. These manipulations can positively impact the treatment of a wide range of neurological and psychiatric disorders by promoting the restorative effects of sleep on memory consolidation, clearance of toxic metabolites, metabolism, and immune function and by decreasing hyperarousal.
睡眠障碍在社会中普遍存在，在军人和退伍军人中更为常见。睡眠和觉醒机制的紊乱在神经精神障碍中很常见，如精神分裂症、创伤后应激障碍、焦虑和情感障碍、创伤性脑损伤、痴呆和物质使用障碍。睡眠障碍加剧了自杀意念，这是退伍军人和普通人群的主要关注点。这些障碍会降低生活质量、影响人际关系、降低工作效率、加重其他疾病的临床特征，并妨碍康复。因此，需要采取措施来改善睡眠和调节觉醒。控制睡眠和觉醒的大脑回路的基础科学研究导致了最近批准了针对食欲素/下丘脑分泌素和组胺系统的新药，补充了影响 GABA 受体和单胺能系统的现有药物。调节睡眠和觉醒的非侵入性脑刺激技术是安全的，具有潜力，但需要进一步发展才能广泛应用。侵入性病毒载体和深部脑刺激方法也处于起步阶段，但可能用于调节严重神经和精神疾病中的睡眠和觉醒。这里介绍的行为、药理学、非侵入性脑刺激和细胞特异性侵入性方法表明，有可能选择性地影响觉醒、睡眠起始、睡眠维持或睡眠阶段特定现象，如睡眠纺锤波或慢波活动。这些操作可以通过促进睡眠对记忆巩固、有毒代谢物清除、代谢和免疫功能的恢复作用，并通过降低过度觉醒，积极影响广泛的神经和精神疾病的治疗。
