Hernandez R Nick, Feinberg Rachel L, Vaurio Rebecca, Passanante Natalie M, Thompson Richard E, Kaufmann Walter E
Kennedy Krieger Institute, Baltimore, MD 21211, USA.
Am J Med Genet A. 2009 Jun;149A(6):1125-37. doi: 10.1002/ajmg.a.32848.
The present study extends our previous work on characterizing the autistic behavior profile of boys with fragile X syndrome (FXS) who meet Diagnostic and Statistical Manual for Mental Disorders, 4th Edition criteria for autism spectrum disorder (ASD) into a longitudinal evaluation of ASD in FXS (FXS + ASD). Specifically, we aimed to determine the stability of the diagnosis and profile of ASD in FXS over time. Through regression models, we also evaluated which autistic and social behaviors and skills were correlates of diagnosis and autistic behavior severity (i.e., Autism Diagnostic Interview-Revised total scores). Finally, we assessed the evolution of cognitive parameters in FXS + ASD. A population of 56 boys (30-88 months at baseline) with FXS was evaluated using measures of autistic, social, and cognitive behaviors and skills at three yearly evaluations. We found that the diagnosis of ASD in FXS was relatively stable over time. Further emphasizing this stability, we found a set of behaviors and skills, particularly those related to peer relationships and adaptive socialization, that differentiated FXS + ASD from the rest of the FXS cohort (FXS + None) and contributed to autistic severity at all time points. Nevertheless, the general improvement in autistic behavior observed in FXS + ASD coupled with the concurrent worsening in FXS + None resulted in less differentiation between the groups over time. Surprisingly, FXS + ASD IQ scores were stable while FXS + None non-verbal IQ scores declined. Our findings indicate that ASD is a distinctive subphenotype in FXS characterized by deficits in complex social interaction, with similarities to ASD in the general population.
本研究扩展了我们之前的工作，即对符合《精神疾病诊断与统计手册》第四版自闭症谱系障碍（ASD）标准的脆性X综合征（FXS）男孩的自闭症行为特征进行研究，将其扩展为对FXS合并ASD（FXS+ASD）患者的ASD纵向评估。具体而言，我们旨在确定FXS患者中ASD诊断和特征随时间的稳定性。通过回归模型，我们还评估了哪些自闭症和社交行为及技能与诊断和自闭症行为严重程度（即《自闭症诊断访谈修订版》总分）相关。最后，我们评估了FXS+ASD患者认知参数的演变。对56名患有FXS的男孩（基线时年龄为30-88个月）进行了评估，在三次年度评估中使用了自闭症、社交和认知行为及技能的测量方法。我们发现，FXS患者中ASD的诊断随时间相对稳定。进一步强调这种稳定性，我们发现了一组行为和技能，特别是那些与同伴关系和适应性社交相关的行为和技能，这些行为和技能将FXS+ASD与其余FXS队列（FXS+无ASD）区分开来，并在所有时间点都对自闭症严重程度有影响。然而，FXS+ASD患者中观察到的自闭症行为总体改善，加上FXS+无ASD患者同时出现的恶化，导致随着时间的推移两组之间的差异减小。令人惊讶的是，FXS+ASD患者的智商分数稳定，而FXS+无ASD患者的非言语智商分数下降。我们的研究结果表明，ASD是FXS中一种独特的亚表型，其特征是复杂社会互动存在缺陷，与普通人群中的ASD相似。
