Centre for Brain and Cognitive Development, Birkbeck, University of London, WC1E 7HX, London, UK.
Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
Sci Transl Med. 2022 Aug 17;14(658):eabf8987. doi: 10.1126/scitranslmed.abf8987.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication, but also great heterogeneity. To offer individualized medicine approaches, we need to better target interventions by stratifying autistic people into subgroups with different biological profiles and/or prognoses. We sought to validate neural responses to faces as a potential stratification factor in ASD by measuring neural (electroencephalography) responses to faces (critical in social interaction) in = 436 children and adults with and without ASD. The speed of early-stage face processing (N170 latency) was on average slower in ASD than in age-matched controls. In addition, N170 latency was associated with responses to faces in the fusiform gyrus, measured with functional magnetic resonance imaging, and polygenic scores for ASD. Within the ASD group, N170 latency predicted change in adaptive socialization skills over an 18-month follow-up period; data-driven clustering identified a subgroup with slower brain responses and poor social prognosis. Use of a distributional data-driven cutoff was associated with predicted improvements of power in simulated clinical trials targeting social functioning. Together, the data provide converging evidence for the utility of the N170 as a stratification factor to identify biologically and prognostically defined subgroups in ASD.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交沟通困难，但也存在很大的异质性。为了提供个体化的医学方法，我们需要通过将自闭症患者分为具有不同生物学特征和/或预后的亚组来更好地确定干预措施的目标。我们试图通过测量 = 436 名患有和不患有 ASD 的儿童和成人对人脸的神经（脑电图）反应来验证将神经反应作为 ASD 潜在分层因素的有效性，因为这些反应对面部识别至关重要，而面部识别在社交互动中非常重要。与年龄匹配的对照组相比，ASD 患者的早期面部处理（N170 潜伏期）速度平均较慢。此外，N170 潜伏期与使用功能磁共振成像测量的梭状回中的面孔反应以及 ASD 的多基因评分有关。在 ASD 组中，N170 潜伏期可以预测 18 个月随访期间适应性社交技能的变化；基于数据的聚类确定了一个具有较慢大脑反应和较差社交预后的亚组。使用基于分布的数据驱动截止值与针对社交功能的模拟临床试验中预测的功效提高相关。综上所述，这些数据为 N170 作为分层因素的有效性提供了有力的证据，可以用于识别具有生物学和预后定义的 ASD 亚组。
