Lurie Family Foundations MEG Imaging Center, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Dev Neurosci. 2019;41(1-2):123-131. doi: 10.1159/000500799. Epub 2019 Jul 5.
47,XYY syndrome (XYY) is one of the common forms of sex chromosome aneuploidy in males. XYY males tend to have tall stature, early speech, motor delays, social and behavioral challenges, and a high rate of language impairment. Recent studies indicate that 20-40% of males with XYY meet diagnostic criteria for autism spectrum disorder (ASD; the rate in the general population is 1-2%). Although many studies have examined the neural correlates of language impairment in ASD, few similar studies have been conducted on individuals with XYY. Studies using magnetoencephalography (MEG) in idiopathic ASD (ASD-I) have demonstrated delayed neurophysiological responses to changes in the auditory stream, revealed in the mismatch negativity or its magnetic counterpart, the mismatch field (MMF). This study investigated whether similar findings are observed in XYY-associated ASD and whether delayed processing is also present in individuals with XYY without ASD. MEG measured MMFs arising from the left and the right superior temporal gyrus during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in children/adolescents with XYY both with and without a diagnosis of ASD, as well as in those with ASD-I and in typically developing controls (TD). Ninety male participants (6-17 years old) were included in the final analyses (TD, n = 38, 11.50 ± 2.88 years; ASD-I, n = 21, 13.83 ± 3.25 years; XYY without ASD, n = 15, 12.65 ± 3.91 years; XYY with ASD, n = 16, 12.62 ± 3.19 years). The groups did not differ significantly in age (p > 0.05). There was a main effect of group on MMF latency (p < 0.001). Delayed MMF latencies were found in participants with XYY both with and without an ASD diagnosis, as well as in the ASD-I group compared to the TD group (ps < 0.001). Furthermore, participants with XYY (with and without ASD) showed a longer MMF latency than the ASD-I group (ps < 0.001). There was, however, no significant difference in MMF latency between individuals with XYY with ASD and those with XYY without ASD. Delayed MMF latencies were associated with severity of language impairment. Our findings suggest that auditory MMF latency delays are pronounced in this specific Y chromosome aneuploidy disorder, both with and without an ASD diagnosis, and thus may implicate the genes of the Y chromosome in mediating atypical MMF activity.
47,XYY 综合征（XYY）是男性中常见的性染色体非整倍体形式之一。XYY 男性往往身材高大、语言发育较早、运动发育迟缓、存在社交和行为挑战，以及语言障碍发生率较高。最近的研究表明，20-40%的 XYY 男性符合自闭症谱系障碍（ASD；一般人群的发病率为 1-2%）的诊断标准。尽管许多研究都检查了 ASD 中语言障碍的神经相关性，但对 XYY 个体进行类似研究的却很少。使用磁共振脑磁图（MEG）对特发性 ASD（ASD-I）进行的研究表明，听觉流中存在神经生理反应延迟，表现在失匹配负波或其磁对应物失匹配场（MMF）中。本研究旨在探讨在 XYY 相关 ASD 中是否也存在类似的发现，以及在没有 ASD 的 XYY 个体中是否也存在延迟处理。MEG 测量了左侧和右侧上颞回在听觉Oddball 范式中产生的 MMF，刺激为元音 (/a/ 和 /u/)，参与者为 XYY 儿童/青少年，他们既有 ASD 也没有 ASD，以及 ASD-I 和典型发育对照组（TD）。最终分析包括 90 名男性参与者（6-17 岁）（TD，n=38，11.50±2.88 岁；ASD-I，n=21，13.83±3.25 岁；XYY 无 ASD，n=15，12.65±3.91 岁；XYY 有 ASD，n=16，12.62±3.19 岁）。组间年龄无显著差异（p＞0.05）。组间 MMF 潜伏期存在主效应（p＜0.001）。XYY 既有 ASD 也没有 ASD 的参与者，以及 ASD-I 组的 MMF 潜伏期均延迟，与 TD 组相比（p＜0.001）。此外，XYY 个体（有和没有 ASD）的 MMF 潜伏期长于 ASD-I 组（p＜0.001）。然而，XYY 有 ASD 和 XYY 无 ASD 的个体之间的 MMF 潜伏期无显著差异。延迟的 MMF 潜伏期与语言障碍的严重程度相关。我们的研究结果表明，这种特定的 Y 染色体非整倍体疾病，无论是有还是没有 ASD 诊断，听觉 MMF 潜伏期均延迟，因此 Y 染色体的基因可能介导了异常 MMF 活性。
