From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands (Bussu, Llera, Buitelaar, Beckmann); the Centre for Brain and Cognitive Development, Birkbeck College, University of London, London, UK (Jones, Johnson); the Department of Child & Adolescent Psychiatry and MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK (Tye); and the Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; South London and Maudsley NHS Foundation Trust (SLaM), London, UK (Charman).
J Psychiatry Neurosci. 2021 Jan 4;46(1):E34-E43. doi: 10.1503/jpn.190148.
Autism spectrum disorder (ASD) is highly heterogeneous in its etiology and manifestation. The neurobiological processes underlying ASD development are reflected in multiple features, from behaviour and cognition to brain functioning. An integrated analysis of these features may optimize the identification of these processes.
We examined cognitive and adaptive functioning and ASD symptoms between 8 and 36 months in 161 infants at familial high risk for ASD and 71 low-risk controls; we also examined neural sensitivity to eye gaze at 8 months in a subsample of 140 high-risk and 61 low-risk infants. We used linked independent component analysis to extract patterns of variation across domains and development, and we selected the patterns significantly associated with clinical classification at 36 months.
An early process at 8 months, indicating high levels of functioning and low levels of symptoms linked to higher attention to gaze shifts, was reduced in infants who developed ASD. A longitudinal process of increasing functioning and low levels of symptoms was reduced in infants who developed ASD, and another process suggesting a stagnation in cognitive functioning at 24 months was increased in infants who developed ASD.
Although the results showed a clear significant trend relating to clinical classification, we found substantial overlap between groups.
We uncovered underlying processes that acted together early in development and were associated with clinical outcomes. Our results highlighted the complexity of emerging ASD, which goes beyond the borders of clinical categories. Future work should integrate genetic data to investigate the specific genetic risks linked to these processes.
自闭症谱系障碍（ASD）在病因和表现上高度异质。ASD 发展的神经生物学过程反映在多个特征上，从行为和认知到大脑功能。对这些特征进行综合分析可能会优化这些过程的识别。
我们在 161 名有 ASD 家族高风险的婴儿和 71 名低风险对照婴儿中，在 8 至 36 个月时检查了认知和适应功能以及 ASD 症状；我们还在 140 名高风险和 61 名低风险婴儿的子样本中，在 8 个月时检查了对眼神注视的神经敏感性。我们使用链接独立成分分析来提取跨领域和发展的变化模式，并选择与 36 个月时临床分类显著相关的模式。
8 个月时的早期过程表明，与高注意力转移注视相关的高水平功能和低水平症状的过程减少了，这与发展为 ASD 的婴儿有关。功能逐渐增加和症状水平较低的纵向过程在发展为 ASD 的婴儿中减少了，而在发展为 ASD 的婴儿中，认知功能在 24 个月时停滞不前的另一个过程增加了。
尽管结果显示出与临床分类相关的明确显著趋势，但我们发现组间存在大量重叠。
我们发现了在发育早期起作用并与临床结果相关的潜在过程。我们的结果强调了新兴 ASD 的复杂性，这超出了临床分类的界限。未来的工作应该整合遗传数据，以研究与这些过程相关的特定遗传风险。
