MIND Institute, University of California, Davis , Sacramento, CA, USA ; Department of Psychiatry and Behavioral Sciences, University of California, Davis , Sacramento, CA, USA.
Front Genet. 2014 Oct 16;5:355. doi: 10.3389/fgene.2014.00355. eCollection 2014.
Autism spectrum disorder (ASD) is a common comorbid condition in people with fragile X syndrome (FXS). It has been assumed that ASD symptoms reflect the same underlying psychological and neurobiological impairments in both FXS and non-syndromic ASD, which has led to the claim that targeted pharmaceutical treatments that are efficacious for core symptoms of FXS are likely to be beneficial for non-syndromic ASD as well. In contrast, we present evidence from a variety of sources suggesting that there are important differences in ASD symptoms, behavioral and psychiatric correlates, and developmental trajectories between individuals with comorbid FXS and ASD and those with non-syndromic ASD. We also present evidence suggesting that social impairments may not distinguish individuals with FXS with and without ASD. Finally, we present data that demonstrate that the neurobiological substrates of the behavioral impairments, including those reflecting core ASD symptoms, are different in FXS and non-syndromic ASD. Together, these data suggest that there are clinically important differences between FXS and non-syndromic ASD that are masked by reliance on the categorical diagnosis of ASD. We argue for use of a symptom-based approach in future research, including studies designed to evaluate treatment efficacy.
自闭症谱系障碍（ASD）是脆性 X 综合征（FXS）患者常见的共患病。人们认为 ASD 症状反映了 FXS 和非综合征性 ASD 中相同的潜在心理和神经生物学损伤，这导致了一种说法，即对 FXS 的核心症状有效的靶向药物治疗也可能对非综合征性 ASD 有益。相比之下，我们从各种来源提供的证据表明，患有共病 FXS 和 ASD 的个体与患有非综合征性 ASD 的个体之间存在 ASD 症状、行为和精神相关症状以及发育轨迹方面的重要差异。我们还提供了证据表明，社交障碍可能无法区分患有和不患有 ASD 的 FXS 个体。最后，我们提供的数据表明，行为障碍的神经生物学基础，包括反映核心 ASD 症状的障碍，在 FXS 和非综合征性 ASD 中是不同的。综上所述，这些数据表明 FXS 和非综合征性 ASD 之间存在临床重要差异，而这些差异被对 ASD 的分类诊断所掩盖。我们主张在未来的研究中采用基于症状的方法，包括旨在评估治疗效果的研究。
