Ji Qi, Li Si-Jia, Zhao Jun-Bo, Xiong Yun, Du Xiao-Hui, Wang Chun-Xiang, Lu Li-Ming, Tan Jing-Yao, Zhu Zhi-Ru
Department of Psychology, Army Medical University, Chongqing, China.
College of Basic Medicine, Army Medical University, Chongqing, China.
Front Psychiatry. 2023 May 2;14:1079683. doi: 10.3389/fpsyt.2023.1079683. eCollection 2023.
The incidence of sleep disorders in children with autism spectrum disorder (ASD) is very high. Sleep disorders can exacerbate the development of ASD and impose a heavy burden on families and society. The pathological mechanism of sleep disorders in autism is complex, but gene mutations and neural abnormalities may be involved.
In this review, we examined literature addressing the genetic and neural mechanisms of sleep disorders in children with ASD. The databases PubMed and Scopus were searched for eligible studies published between 2013 and 2023.
Prolonged awakenings of children with ASD may be caused by the following processes. Mutations in the and genes can decrease GABA inhibition on neurons in the locus coeruleus, leading to hyperactivity of noradrenergic neurons and prolonged awakenings in children with ASD. Mutations in the , and genes heighten the expression of histamine receptors in the posterior hypothalamus, potentially intensifying histamine's ability to promote arousal. Mutations in the and genes cause atypical modulation of amygdala impact on orexinergic neurons, potentially causing hyperexcitability of the hypothalamic orexin system. Mutations in the , , , and genes affect dopamine synthesis, catabolism, and reuptake processes, which can elevate dopamine concentrations in the midbrain. Secondly, non-rapid eye movement sleep disorder is closely related to the lack of butyric acid, iron deficiency and dysfunction of the thalamic reticular nucleus induced by gene alterations. Thirdly, mutations in the , , , , and genes induce structural and functional abnormalities of the dorsal raphe nucleus (DRN) and amygdala, which may disturb REM sleep. In addition, the decrease in melatonin levels caused by , , and gene mutations, along with functional abnormalities of basal forebrain cholinergic neurons, may lead to abnormal sleep-wake rhythm transitions.
Our review revealed that the functional and structural abnormalities of sleep-wake related neural circuits induced by gene mutations are strongly correlated with sleep disorders in children with ASD. Exploring the neural mechanisms of sleep disorders and the underlying genetic pathology in children with ASD is significant for further studies of therapy.
自闭症谱系障碍（ASD）儿童睡眠障碍的发生率非常高。睡眠障碍会加剧ASD的发展，并给家庭和社会带来沉重负担。自闭症睡眠障碍的病理机制复杂，但可能涉及基因突变和神经异常。
在本综述中，我们研究了关于ASD儿童睡眠障碍的遗传和神经机制的文献。检索了PubMed和Scopus数据库中2013年至2023年发表的符合条件的研究。
ASD儿童长时间觉醒可能由以下过程引起。 和 基因的突变可降低蓝斑中神经元的GABA抑制作用，导致去甲肾上腺素能神经元活动亢进，从而使ASD儿童长时间觉醒。 、 和 基因的突变会提高下丘脑后部组胺受体的表达，可能增强组胺促进觉醒的能力。 和 基因的突变导致杏仁核对食欲素能神经元的影响出现非典型调节，可能导致下丘脑食欲素系统过度兴奋。 、 、 和 基因的突变影响多巴胺的合成、分解代谢和再摄取过程，可提高中脑多巴胺浓度。其次，非快速眼动睡眠障碍与丁酸缺乏、铁缺乏以及 基因改变引起的丘脑网状核功能障碍密切相关。第三， 、 、 、 、 和 基因的突变会导致中缝背核（DRN）和杏仁核的结构和功能异常，这可能会干扰快速眼动睡眠。此外， 、 和 基因突变导致褪黑素水平降低，以及基底前脑胆碱能神经元功能异常，可能导致睡眠-觉醒节律转换异常。
我们的综述表明，基因突变引起的睡眠-觉醒相关神经回路的功能和结构异常与ASD儿童的睡眠障碍密切相关。探索ASD儿童睡眠障碍的神经机制和潜在的遗传病理学对于进一步的治疗研究具有重要意义。
