Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor α autoimmune disorder

内分泌学 内科学 甲状腺 反三碘甲状腺原氨酸 自闭症谱系障碍 三碘甲状腺素 激素 先天性甲状腺功能减退 易怒 医学 下丘脑-垂体-甲状腺轴 TRH刺激试验 自闭症 促甲状腺素释放激素 精神科 更年期
作者
Richard E. Frye,Rebecca Wynne,Shannon Rose,John C. Slattery,Leanna Delhey,Marie Tippett,Stephen G. Kahler,Sirish C. Bennuri,Stepan Melnyk,Jeffrey M. Sequeira,Edward V. Quadros
出处
期刊:Journal of Neuroendocrinology [Wiley]
卷期号:29 (3) 被引量:35
标识
DOI:10.1111/jne.12461
摘要

Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid-stimulating hormone (TSH), free thyroxine (T4) (FT4), total triiodothyronine (T3) (TT3), reverse T3 (rT3), thyroid-releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behaviour and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points. To better understand the significance of the FRα in relation to thyroid development, we examined FRα expression on prenatal and postnatal thyroid. TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT4 was rarely outside the normal range. TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titres. On repeated measurements, changes in TSH and FT4/TSH ratio were found to correspond to changes in blocking FRAA titres. TSH and the FT4/TSH, TT3/TSH and rT3/TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale (SRS), whereas TT3 was associated with SRS subscales and TRH was related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FRα expression during the early prenatal period, although expression decreased significantly in later gestation and postnatal thyroid tissue. The results of the present study suggest that thyroid dysfunction in ASD may be related to blocking FRAA. The high expression of FRα in the early foetal thyroid suggests that foetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD.
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