Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review

Abstract

BackgroundThe 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.MethodsIn 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.ResultsProlonged awakenings of children with ASD may be caused by the following processes. Mutations in the MECP2, VGAT and SLC6A1 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 HRH1, HRH2, and HRH3 genes heighten the expression of histamine receptors in the posterior hypothalamus, potentially intensifying histamine’s ability to promote arousal. Mutations in the KCNQ3 and PCDH10 genes cause atypical modulation of amygdala impact on orexinergic neurons, potentially causing hyperexcitability of the hypothalamic orexin system. Mutations in the AHI1, ARHGEF10, UBE3A, and SLC6A3 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 PTCHD1 gene alterations. Thirdly, mutations in the HTR2A, SLC6A4, MAOA, MAOB, TPH2, VMATs, SHANK3, and CADPS2 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 ASMT, MTNR1A, and MTNR1B gene mutations, along with functional abnormalities of basal forebrain cholinergic neurons, may lead to abnormal sleep–wake rhythm transitions.ConclusionOur 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.

PTCHD1 gene mutation/deletion: the cognitive-behavioral phenotyping of four case reports

“…Previous studies ( 1–3 , 35 ) have already documented ID, ASD, global developmental delay, infantile hypotonia, and motor incoordination in individuals with PTCHD1 microdeletions or mutations. Some patients may also exhibit aggressive behavior, sleep disorders, ADHD, and other psychiatric issues ( 1 , 36 , 37 ) suggesting PTCHD1 ’s possible involvement in overlapping phenotypes in the spectrum of intellectual, neurodevelopmental, and autism disorders. With the aim to further contribute to the cognitive – behavioral phenotyping of PTCHD1 disorders, in this study, we report the neuropsychological and psychopathological profiles of four patients, providing quantitative data from standardized evaluations.…”

The genome of African manatee Trichechus senegalensis reveals secondary adaptation to the aquatic environment

“…The CADPS2 -null mice showed defects in sleep/wake regulation and circadian rhythm. 24 To sum up, all of these aforementioned genes were associated with the adaptive phenotypes in fully aquatic mammals.…”

“…Among these, CADPS2 -null mice showed defects in sleep/wake regulation and circadian rhythm; meanwhile, mutations in the CADPS2 gene induce structural and functional abnormalities of the dorsal raphe nucleus and amygdala, which may lead to REM sleep disorder. 24 The convergent AA substitution located in the CADPS2 may play an important role in limiting REM sleep for fully aquatic mammals, although validation requires functional experiments.…”

Exploring the mechanism of agarwood moxa smoke in treating sleep disorders based on GC–MS and network pharmacology

“…Among them, dopaminergic synapses are chemical synapses that play a crucial role in emotional disorders and can affect the connections of all members of the axonal protein superfamily of transmembrane molecules that play essential roles in neuropsychiatric disorders and excitatory cells. Excessive activation of the renin-angiotensin system pathway can lead to disturbances in the internal environment, increased reabsorption of Na + by the renal tubules, and elevated levels of renin and angiotensin, leading to elevated blood pressure, insomnia, anxiety, depression, and inflammation ( 45 , 46 ). When insomnia occurs in the human body, the transmission of excitation signaling pathways is enhanced, and the content of molecules related to this pathway also increases.…”