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Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances
Journal of Pineal Research ( IF 8.3 ) Pub Date : 2021-01-09 , DOI: 10.1111/jpi.12715
Sanseray da Silveira Cruz-Machado 1 , Leila Maria Guissoni Campos 2 , Cintia Cristina Fadini 3 , George Anderson 4 , Regina P Markus 1 , Luciana Pinato 3
Affiliation  

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6‐sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin‐6 (IL‐6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night‐time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P < .05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL‐6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night‐time aMT6s excretion (r = −.28, P < .05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r = −.31, P < .05) and positively associated with TNF level (r = .42, P < .01). Overall such data indicate immune‐pineal axis activation, with elevated TNF but not IL‐6 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune‐inflammatory activity. Such two‐way interactions of the immune‐pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.

中文翻译:

自闭症患者夜间褪黑激素紊乱:与肿瘤坏死因子和睡眠障碍的关联

睡眠障碍、褪黑激素分泌异常和炎症增加是自闭症谱系障碍 (ASD) 病理生理学的一个方面。本研究评估了 20 名对照组和 20 名 ASD 参与者的每日尿 6-磺基褪黑激素 (aMT6s) 排泄情况以及肿瘤坏死因子 (TNF) 和白细胞介素-6 (IL-6) 的唾液水平,并将这些测量与睡眠障碍。尽管 60% 的 ASD 参与者夜间 aMT6s 排泄量显着上升,但与对照组相比,这种上升显着减弱(P < .05)。其余 40% 的 ASD 个体夜间 aMT6s 没有显着增加。ASD 个体夜间唾液 TNF 水平较高,但没有 IL-6。睡眠开始和维持功能障碍,如儿童睡眠障碍量表所示,与夜间 aMT6s 排泄相关 ( r  = -.28, P  < .05)。睡眠呼吸功能障碍与 aMT6s 呈负相关 ( r  = -.31, P  < .05) 并与 TNF 水平呈正相关 ( r  = .42, P < .01)。总体而言,这些数据表明免疫松果体轴激活,TNF 升高但 IL-6 水平与 ASD 中松果体褪黑激素释放中断和睡眠功能障碍相关。有人提出,ASD 的昼夜节律失调与免疫炎症活动的增强密切相关。免疫松果体轴的这种双向相互作用可能支持 ASD 病理生理学的许多方面,包括睡眠障碍以及认知和行为改变。
更新日期:2021-01-09
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