自闭症谱系障碍中变异对皮质结构改变的转化探索。
A translational exploration of the effects of variants on altered cortical structures in autism spectrum disorder.
机构信息
From the Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan (Chien, Chen, Chiu, Tsai, Gau); and the Graduate Institute of Clinical Medicine, and Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan (Chen, Gau).
From the Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan (Chien, Chen, Chiu, Tsai, Gau); and the Graduate Institute of Clinical Medicine, and Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan (Chen, Gau)
出版信息
J Psychiatry Neurosci. 2021 Dec 3;46(6):E647-E658. doi: 10.1503/jpn.210022. Print 2021 Nov-Dec.
BACKGROUND
Evidence suggests that cortical anatomy may be aytpical in autism spectrum disorder. The wingless-type MMTV integration site family, member 2 ), a candidate gene for autism spectrum disorder, may regulate cortical development. However, it is unclear whether variants are associated with altered cortical thickness in autism spectrum disorder.
METHODS
In a sample of 118 people with autism spectrum disorder and 122 typically developing controls, we investigated cortical thickness using FreeSurfer software. We then examined the main effects of the variants and the interactions of group × SNP and age × SNP for each hemisphere and brain region that was altered in people with autism spectrum disorder.
RESULTS
Compared to neurotypical controls, people with autism spectrum disorder showed reduced mean cortical thickness in both hemispheres and 9 cortical regions after false discovery rate correction, including the right cingulate gyrus, the orbital gyrus, the insula, the inferior frontal gyrus (orbital part and triangular part), the lateral occipitotemporal gyrus, the posterior transverse collateral sulcus, the lateral sulcus and the superior temporal sulcus. In the full sample, 2 SNPs of (rs6950765 and rs2896218) showed age × SNP interactions for the mean cortical thickness of both hemispheres, the middle-posterior cingulate cortex and the superior temporal cortex.
LIMITATIONS
We examined the genetic effect for each hemisphere and the 9 regions that were altered in autism spectrum disorder. The age effect we found in this cross-sectional study needs to be examined in longitudinal studies.
CONCLUSION
Based on neuroimaging and genetic data, our findings suggest that variants might be associated with altered cortical thickness in autism spectrum disorder. Whether and how these variants might involve cortical thinning requires further investigation.
TRIAL REGISTRATION
ClinicalTrials.gov no. NCT01582256.
PROTOCOL REGISTRATION
National Institutes of Health no. NCT00494754.
背景
有证据表明，皮质解剖结构在自闭症谱系障碍中可能存在异常。Wingless 型 MMTV 整合位点家族成员 2（WNT2）是自闭症谱系障碍的候选基因，可能调节皮质发育。然而，目前尚不清楚 变异是否与自闭症谱系障碍患者的皮质厚度改变有关。
方法
在 118 名自闭症谱系障碍患者和 122 名典型发育对照者样本中，我们使用 FreeSurfer 软件研究皮质厚度。然后，我们检查了 变体的主要效应以及组×SNP 和年龄×SNP 的相互作用，每个脑区都是自闭症谱系障碍患者改变的。
结果
与神经典型对照组相比，经假发现率校正后，自闭症谱系障碍患者双侧半球和 9 个皮质区域的平均皮质厚度均降低，包括右侧扣带回、眶额回、岛叶、下额回（眶部和三角部）、外侧枕颞回、后横 collateral 沟、外侧裂和颞上回。在全样本中，2 个 （rs6950765 和 rs2896218）的 SNP 显示出双侧半球、中后扣带皮层和颞上皮层平均皮质厚度的年龄×SNP 相互作用。
局限性
我们检查了每个半球和自闭症谱系障碍中改变的 9 个区域的遗传效应。我们在横断面研究中发现的年龄效应需要在纵向研究中进行检查。
结论
基于神经影像学和遗传学数据，我们的发现表明， 变异可能与自闭症谱系障碍患者的皮质厚度改变有关。这些 变异是否以及如何涉及皮质变薄需要进一步研究。
试验注册
ClinicalTrials.gov 编号：NCT01582256。
方案注册
美国国立卫生研究院编号：NCT00494754。
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