Objective:

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is associated with significant difficulties in adaptive behavior and variation in clinical outcomes across the life span. Some individuals with ASD improve, whereas others may not change significantly, or regress. Hence, the development of “personalized medicine” approaches is essential. However, this requires an understanding of the biological processes underpinning differences in clinical outcome, at both the individual and subgroup levels, across the lifespan.

Methods:

The authors conducted a longitudinal follow-up study of 483 individuals (204 with ASD and 279 neurotypical individuals, ages 6–30 years), with assessment time points separated by ∼12–24 months. Data collected included behavioral data (Vineland Adaptive Behavior Scale–II), neuroanatomical data (structural MRI), and genetic data (DNA). Individuals with ASD were grouped into clinically meaningful “increasers,” “no-changers,” and “decreasers” in adaptive behavior. First, the authors compared neuroanatomy between outcome groups. Next, they examined whether deviations from the neurotypical neuroanatomical profile were associated with outcome at the individual level. Finally, they explored the observed neuroanatomical differences’ potential genetic underpinnings.

Results:

Outcome groups differed in neuroanatomical features (cortical volume and thickness, surface area), including in “social brain” regions previously implicated in ASD. Also, deviations of neuroanatomical features from the neurotypical profile predicted outcome at the individual level. Moreover, neuroanatomical differences were associated with genetic processes relevant to neuroanatomical phenotypes (e.g., synaptic development).

Conclusions:

This study demonstrates, for the first time, that variation in clinical (adaptive) outcome is associated with both group- and individual-level variation in anatomy of brain regions enriched for genes relevant to ASD. This may facilitate the move toward better targeted/precision medicine approaches.

中文翻译：

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自闭症适应行为变化的神经生物学相关性

客观的：

自闭症谱系障碍 (ASD) 是一种终生的神经发育疾病，与适应行为的显着困难和终生临床结果的变化有关。一些患有 ASD 的人有所改善，而其他人可能没有显着变化或退化。因此，发展“个性化医疗”方法至关重要。然而，这需要了解在整个生命周期中个体和亚组水平上临床结果差异的生物学过程。

方法：

作者对 483 名个体（204 名患有 ASD 和 279 名神经典型个体，年龄 6-30 岁）进行了纵向跟踪研究，评估时间点相隔 12-24 个月。收集的数据包括行为数据（Vineland Adaptive Behavior Scale-II）、神经解剖学数据（结构 MRI）和遗传数据（DNA）。患有 ASD 的个体被分为适应行为有临床意义的“增加者”、“不变者”和“降低者”。首先，作者比较了结果组之间的神经解剖学。接下来，他们检查了与神经典型神经解剖学特征的偏差是否与个体水平的结果相关。最后，他们探索了观察到的神经解剖学差异的潜在遗传基础。

结果：

结果组在神经解剖学特征（皮质体积和厚度、表面积）方面存在差异，包括先前与 ASD 相关的“社交大脑”区域。此外，神经解剖学特征与神经典型特征的偏差预测了个体水平的结果。此外，神经解剖学差异与与神经解剖学表型相关的遗传过程（例如，突触发育）有关。

结论：

这项研究首次证明，临床（适应性）结果的变化与富含 ASD 相关基因的大脑区域解剖结构的群体和个体水平变化有关。这可能有助于向更好的靶向/精准医学方法迈进。