Department of Neuroscience, NIH-UCSD Autism Center of Excellence, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
JAMA. 2011 Nov 9;306(18):2001-10. doi: 10.1001/jama.2011.1638.
Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.
To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES: Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006.
Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed.
Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, -8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children.
In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.
自闭症通常涉及早期大脑过度生长，包括前额叶皮层（PFC）。尽管前额叶异常被认为是一些自闭症症状的基础，但导致过度生长的细胞缺陷仍不清楚。
研究自闭症儿童的早期大脑过度生长是否涉及 PFC 中神经元数量过多。
设计、环境和案例：由经验丰富的解剖学家对来自 7 名自闭症和 6 名年龄在 2 至 16 岁的男性对照组儿童的死后前额叶组织进行检查，这些解剖学家对诊断状况一无所知。使用立体学方法在前额叶外侧（DL-PFC）和内侧（M-PFC）分区内定量测量神经元的数量和大小。这些病例来自美国东部和东南部，死亡时间在 2000 年至 2006 年之间。
比较自闭症和对照组死后病例的 DL-PFC 和 M-PFC 中平均神经元数量和大小。还进行了神经元数量与脑重偏离年龄正常值的相关性分析。
自闭症儿童的 PFC 神经元数量比对照组多 67%（平均，19.4 亿个；95%置信区间，15.71-23.11 个），包括 DL-PFC 多 79%（15.71 亿个；95%置信区间，12.00-19.44 个），M-PFC 多 29%（3.60 亿个；95%置信区间，3.30-4.00 个）。自闭症病例的脑重与年龄正常均值相差 17.6%（95%置信区间，10.2%-25.0%；P =.001），而对照组相差 0.2%（95%置信区间，-8.7%至 9.1%；P =.96）。按重量绘制的计数图显示，自闭症儿童的总前额叶神经元计数和脑重均高于对照组儿童。
在这项小型初步研究中，自闭症男性的大脑过度生长涉及 PFC 中异常过多的神经元。
