Nyström Pär, Gredebäck Gustaf, Bölte Sven, Falck-Ytter Terje
Uppsala Child & Babylab, Department of Psychology, Uppsala University, Uppsala, Sweden.
Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Pediatric Neuropsychiatry Unit, Department of Women's & Children's Health, Karolinska Institutet, Stockholm, Sweden ; Division of Child and Adolescent Psychiatry, Stockholm County Council, Stockholm, Sweden.
Mol Autism. 2015 Mar 3;6:10. doi: 10.1186/s13229-015-0011-6. eCollection 2015.
Post mortem brain tissue data and animal modeling work indicate cholinergic disruptions in autism. Moreover, the cholinergic system plays a key role in the early neurodevelopmental processes believed to be derailed early in life in individuals with the disorder. Yet, there is no data from human infants supporting a developmentally important role of this neurotransmitter system. Because the pupillary light reflex depends largely on cholinergic synaptic transmission, we assessed this reflex in a sample of infants at risk for autism as well as infants at low (average) risk.
Ten-month-old infants with an older sibling with autism (n = 29, 16 females), and thus a genetic predisposition to developing the disorder themselves, were presented with white flashes on a computer monitor, and pupillary responses were captured using eye tracking. A control group matched on age and developmental level (n = 15, seven females) was also tested.
The siblings of children with autism had a faster and stronger pupillary light reflex compared to control infants. Baseline pupil diameter was equal in the two groups, ruling out tonic autonomic imbalance as an explanation for these differences.
This study establishes that infant siblings of children with autism have hypersensitive pupillary light reflexes, a result which supports the view that altered sensory processing in infancy is associated with elevated autism risk. Moreover, the study indicates that individual differences in autism susceptibility are linked to differences in the cholinergic system during an early developmental period.
尸检脑组织数据和动物模型研究表明，自闭症存在胆碱能功能紊乱。此外，胆碱能系统在早期神经发育过程中起关键作用，而这一过程在自闭症患者生命早期就出现异常。然而，尚无来自人类婴儿的数据支持该神经递质系统在发育过程中的重要作用。由于瞳孔对光反射很大程度上依赖胆碱能突触传递，我们对一组自闭症高危婴儿以及低（平均）风险婴儿的该反射进行了评估。
选取29名（16名女性）有自闭症同胞兄弟姐妹的10月龄婴儿，这些婴儿因此具有患自闭症的遗传易感性，在电脑屏幕上向他们展示白色闪光，并使用眼动追踪技术记录瞳孔反应。同时对一组年龄和发育水平匹配的对照组婴儿（15名，7名女性）进行测试。
与对照组婴儿相比，自闭症患儿的兄弟姐妹具有更快更强的瞳孔对光反射。两组的基线瞳孔直径相等，排除了紧张性自主神经失衡作为这些差异的解释。
本研究证实，自闭症患儿的同胞兄弟姐妹婴儿具有超敏瞳孔对光反射，这一结果支持了婴儿期感觉加工改变与自闭症风险升高相关的观点。此外，该研究表明，自闭症易感性的个体差异与早期发育阶段胆碱能系统的差异有关。
