Center of Neurodevelopmental Disorders (KIND), Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
Mol Psychiatry. 2018 Jul;23(7):1659-1665. doi: 10.1038/mp.2017.160. Epub 2017 Aug 1.
Autism spectrum disorder (ASD) has been found to be associated with alterations in resting state (RS) functional connectivity, including areas forming the default mode network (DMN) and salience network (SN). However, insufficient control for confounding genetic and environmental influences and other methodological issues limit the generalizability of previous findings. Moreover, it has been hypothesized that ASD might be marked by early hyper-connectivity followed by later hypo-connectivity. To date, only a few studies have explicitly tested age-related influences on RS connectivity alterations in ASD. Using a within-twin pair design (N=150 twins; 8-23 years), we examined altered RS connectivity between core regions of the DMN and SN in relation to autistic trait severity and age in a sample of monozygotic (MZ) and dizygotic (DZ) twins showing typical development, ASD or other neurodevelopmental conditions. Connectivity between core regions of the SN was stronger in twins with higher autistic traits compared to their co-twins. This effect was significant both in the total sample and in MZ twins alone, highlighting the effect of non-shared environmental factors on the link between SN-connectivity and autistic traits. While this link was strongest in children, we did not identify differences between age groups for the SN. In contrast, connectivity between core hubs of the DMN was negatively correlated with autistic traits in adolescents and showed a similar trend in adults but not in children. The results support hypotheses of age-dependent altered RS connectivity in ASD, making altered SN and DMN connectivity promising candidate biomarkers for ASD.
自闭症谱系障碍 (ASD) 与静息状态 (RS) 功能连接的改变有关，包括形成默认模式网络 (DMN) 和突显网络 (SN) 的区域。然而，由于混杂的遗传和环境影响以及其他方法学问题的控制不足，限制了先前发现的普遍性。此外，有人假设 ASD 可能以早期的过度连接为特征，随后是后期的连接不足。迄今为止，只有少数研究明确测试了 ASD 中 RS 连接改变与年龄的关系。我们使用双胞胎内对设计（N=150 对双胞胎；8-23 岁），在一组表现出典型发育、ASD 或其他神经发育状况的同卵（MZ）和异卵（DZ）双胞胎中，检查了 DMN 和 SN 的核心区域之间与自闭症特征严重程度和年龄相关的改变的 RS 连接。与同卵双胞胎相比，具有较高自闭症特征的双胞胎之间的 SN 核心区域之间的连接更强。这一效应在总样本和 MZ 双胞胎中均显著，突出了非共享环境因素对 SN 连接与自闭症特征之间联系的影响。虽然这一联系在儿童中最强，但我们没有发现 SN 在年龄组之间的差异。相比之下，DMN 核心枢纽之间的连接与青少年的自闭症特征呈负相关，在成人中也表现出类似的趋势，但在儿童中没有。研究结果支持 ASD 中 RS 连接随年龄变化的假设，使改变的 SN 和 DMN 连接成为 ASD 的有前途的候选生物标志物。
