Early brain development in infants at high risk for autism spectrum disorder

Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development1, 2. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life3, 4. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6–12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

自闭症谱系障碍（autism spectrum disorder，ASD）患儿已被观察到存在脑体积增大的现象，但该现象的发生时序，以及ASD与行为症状出现之间的关联仍尚不明确。针对两岁儿童的回顾性头围测量与纵向脑容量研究（后续随访至四岁）已提供证据表明，脑容量增加可能在发育早期便已出现¹,²。针对具有自闭症高家族风险的婴儿开展的研究，可助力阐明自闭症的早期发育进程，相关研究已证实ASD的特征性社交缺陷会在出生后第一年的后半段及第二年显现³,⁴。上述观察结果提示，针对ASD高家族风险婴儿开展的前瞻性脑成像研究，或可识别出ASD确诊前就已出现的产后早期脑容量变化。在这项针对106名ASD高家族风险婴儿与42名低风险婴儿的前瞻性神经成像研究中，我们发现，在24个月时被确诊为自闭症的15名高风险婴儿中，6至12月龄期间的皮层表面积过度扩张，先于12至24月龄期间观察到的脑容量过度增长。脑容量过度增长与自闭症社交缺陷的出现及严重程度相关。一种主要基于6至12月龄个体脑部磁共振成像（magnetic resonance imaging）的表面积信息的深度学习算法，可在24个月时预测高风险儿童的自闭症诊断（阳性预测值为81%，灵敏度为88%）。上述研究结果表明，早期脑部变化发生在自闭症行为首次显现的时期。