Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances
Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances
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DOI：
10.1111/jpi.12715
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发表时间：
2021-01-26
影响因子：
10.3
通讯作者：
Pinato, Luciana
中科院分区：
文献类型：
--
作者：
da Silveira Cruz-Machado, Sanseray;Guissoni Campos, Leila Maria;Pinato, Luciana
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-亚硫代褪黑素（aMT6s）排泄情况以及唾液中肿瘤坏死因子（TNF）和白细胞介素-6 （IL-6）水平，并将这些指标与睡眠障碍进行了关联。尽管60%的ASD参与者夜间aMT6s排泄明显上升，但与对照组相比，这种上升明显减弱（P < 0.05）。其余40%的ASD患者夜间amt6没有明显增加。ASD个体夜间唾液TNF水平较高，但IL-6水平不高。儿童睡眠障碍量表显示，睡眠开始和维持功能障碍与夜间aMT6s排泄相关（r = - 0.28, P < 0.05）。睡眠呼吸功能障碍与aMT6s呈负相关（r = - 0.31, P < 0.05），与TNF水平呈正相关（r = 0.42, P < 0.01）。总的来说，这些数据表明免疫-松果体轴激活，TNF升高而非IL-6水平与ASD中松果体褪黑激素释放中断和睡眠障碍相关。有人提出，ASD的昼夜节律失调与免疫炎症活性升高密切相关。这种免疫-松果体轴的双向相互作用可能是ASD病理生理学的许多方面的基础，包括睡眠障碍，以及认知和行为改变。
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.