Schneider A, Johnston C, Tassone F, Sansone S, Hagerman R J, Ferrer E, Rivera S M, Hessl D
a MIND Institute, UC Davis Medical Center , Sacramento , CA , USA.
c Department of Pediatrics , UC Davis School of Medicine , Sacramento , CA , USA.
Clin Neuropsychol. 2016 Aug;30(6):929-43. doi: 10.1080/13854046.2016.1189536. Epub 2016 Jun 29.
Clinical observations and a limited number of research studies provide evidence that the fragile X premutation may confer risk for autism, executive dysfunction, and psychopathology. The link to autism spectrum symptoms and social cognition deficits with the premutation remains uncertain, and thus was the focus of the present investigation.
Our sample included 131 individuals, 42 men/22 women with the FMR1 premutation (mean age = 31.83 ± 8.59 years) with a normal neurological exam, and 48 men/19 women healthy age-matched controls (mean age = 29.48 ± 7.29 years). Individuals completed a comprehensive neuropsychological battery with additional assessments for social cognition, broad autism spectrum, and obsessive-compulsive (OC) symptoms.
Premutation carriers self-reported higher rates of autism-related symptoms (Autism Quotient; p = .001). Among males only, premutation carriers showed more atypical social interaction (p < .001) and stereotyped behavior (p = .014) during standardized clinical examination on the Autism Diagnostic Observation Schedule (ADOS) relative to controls. Female premutation carriers reported significantly higher rates of OC symptoms compared to control females (p = .012). Molecular measures defining the expanded premutation (FMR1 CGG repeat length and/or mRNA) were significantly associated with a measure of theory of mind (Reading the Mind in the Eyes Task).
The results of this study indicate a higher rate of broad autism spectrum symptoms in some males with the premutation and provide evidence for an obsessive-compulsive subtype in female premutation carriers.
临床观察和有限数量的研究表明，脆性X前突变可能会增加患自闭症、执行功能障碍和精神病理学的风险。前突变与自闭症谱系症状和社会认知缺陷之间的联系仍不确定，因此是本研究的重点。
我们的样本包括131名个体，其中42名男性/22名女性携带FMR1前突变（平均年龄 = 31.83 ± 8.59岁），神经学检查正常，以及48名男性/19名女性年龄匹配的健康对照（平均年龄 = 29.48 ± 7.29岁）。个体完成了一套全面的神经心理学测试，并对社会认知、广泛自闭症谱系和强迫症状进行了额外评估。
前突变携带者自我报告的自闭症相关症状发生率较高（自闭症商数；p = 0.001）。仅在男性中，与对照组相比，前突变携带者在自闭症诊断观察量表（ADOS）的标准化临床检查中表现出更多非典型社交互动（p < 0.001）和刻板行为（p = 0.014）。与对照女性相比，女性前突变携带者报告的强迫症状发生率显著更高（p = 0.012）。定义扩展前突变的分子指标（FMR1 CGG重复长度和/或mRNA）与心理理论指标（读心术任务）显著相关。
本研究结果表明，一些携带前突变的男性中广泛自闭症谱系症状的发生率较高，并为女性前突变携带者中的强迫亚型提供了证据。
