Increased neuron number and head size in autism.
Increased neuron number and head size in autism.
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DOI：
10.1001/jama.2011.1633
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
J. Lainhart;N. Lange
中科院分区：
文献类型：
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作者：
J. Lainhart;N. Lange
在这一期的《美国医学会杂志》上，库切斯内及其同事的报告1记录了自闭症患者神经元数量intheprefrontalcortex(PFC)inmalechildrenandadolescents的增加。这些发现建立在利奥·坎纳1943年的原始观察和20年来对自闭症大头症的研究的基础上。平均20%的自闭症患者会发生巨头畸形，通常是由于大脑--儿童时期大脑异常增大所致。3头在出生后18个月内加速生长时的enlargementisrarelypresentatbirth；itdevelopsduringearlychildhood。4平均总大脑、脑叶、白质和灰质体积，包括皮质体积，与典型的发育迟缓和非自闭症发育迟缓的人相比，是significantlyincreasedby2to3yearsofageinchildrenwith自闭症。5-7头部和大脑的过度生长发生在大多数疾病的临床表现之前，这增加了导致过度生长的机制在自闭症的初级发育性神经病理中也发挥作用的可能性。Courchesne等人的这项研究的目的是在细胞水平上调查自闭症患者大脑过度生长的神经基础。在这项尸检组织研究中，研究人员专注于皮质灰质，特别是前额叶，这是与这种疾病高度相关的大脑区域之一，andsoughttoansweracriticalquestioninautismresearch：大脑过度生长是否与神经元、神经胶质细胞的大小和数量增加有关，还是两者兼而有之？研究人员发现，与正常发育儿童(对照组)的6个大脑相比，自闭症男孩的7个大脑中，背外侧PFC(DL-PFC)和内侧PFC(M-PFC)的神经元分别增加了79%和29%。在神经元大小或神经胶质细胞计数方面没有明显的组间差异。对照组前额叶神经元数量与脑重量显著相关，而孤独症组无相关性。作者推测，后一项发现可能表明，一些自闭症患者的大脑相对于他们的前额叶皮质神经元数量来说偏小。同样可能的是由Courchesne等人进行的研究中的increaseofprefrontalcorticalneuronnumberanddensityrelativetotypicalbrainweight.Thebrainsofautismcases3and 4是这种替代解释的具体例子，具有增加的PFC中神经元的数量(22.1亿和21.8亿；文章1中的表5)，并且权重在控制脑重的范围内。自闭症研究中的死后脑组织研究，通常很难进行，因为大脑样本的可获得性有限，样本没有代表性，死亡原因可变，死亡间隔可能很长，以及脑提取、切片和tissueprocessingprotocolsandcellcountingmethods.方面的差异。8大多数(如果不是全部)病例对照组织样本量很小，并且不存在具有代表性的基于人群的死后参考数据，类似于目前从大的儿科活体脑成像标准样本中获得的数据。
N THIS ISSUE OF JAMA, THE REPORT BY COURCHESNE AND colleagues 1 documents an increase in neuron number intheprefrontalcortex(PFC)inmalechildrenandadolescents with autism. Those findings build on Leo Kanner’s original observations 2 in 1943 and 2 decades of recent research investigating macrocephaly in autism. Macrocephaly occurs in 20% of individuals with autism on average and is usually due to megalencephaly—abnormal enlargement of the brain during childhood. 3 The enlargementisrarelypresentatbirth;itdevelopsduringearlychildhood when head growth accelerates during the first 18 months of life. 4 Mean total brain, lobar, white matter, and gray matter volumes, including volume of the cortex, are significantlyincreasedby2to3yearsofageinchildrenwith autism when compared with typically developing and also nonautistic developmentally delayed individuals. 5-7 The excessive head growth and brain growth occur prior to most clinical manifestations of the disorder, raising the possibility that the mechanisms that cause excessive growth also play a role in the primary developmental neuropathology of autism. The purpose of the study by Courchesne et al 1 was to investigate the neural underpinnings of brain overgrowth in autismat the cellular level. In this postmortemtissue study, the investigators focused on cortical gray matter, specifically the PFC, which is one of the brain regions highly implicatedinthedisorder,andsoughttoansweracriticalquestioninautismresearch: is brain overgrowthassociated with increased size and number of neurons, glial cells, or both? The investigators found 79% more neurons in the dorsolateral PFC (DL-PFC) and 29% more neurons in the mesial PFC (M-PFC) in 7 brains from boys with autism compared with 6 brains of typically developing children (controls). There were no apparent group differences in neuron size or in glial cell counts. Prefrontal neuron number and brain weight were significantly correlated in the control group but not in the autism group. The authors speculated that the latter finding may indicate that the brains of some individuals with autism are undersized relative to their prefrontal cortical neuron count. Equally possible is an increaseofprefrontalcorticalneuronnumberanddensityrelativetotypicalbrainweight.Thebrainsofautismcases3and 4 in the study by Courchesne et al 1 are specific examples of such an alternative explanation, having increased numbers of neurons in the PFC (2.21 and 2.18 billion; eTable 5 in the article 1 ) and weights within the range of control brain weights. Postmortem brain tissue studies in autism research, and in general, are difficult to conduct due to limited availability of brain samples, non-representativeness of the samples, variable causes of death, potentially long postmortem intervals, and differences in brain extraction, sectioning and tissueprocessingprotocolsandcellcountingmethods. 8 Most if not all case-control tissue sample sizes are small, and representative population-based postmortem reference data, similar to those currently available from large normative samples of in vivo pediatric brain imaging, 9 do not exist.