Billeci Lucia, Calderoni Sara, Conti Eugenia, Lagomarsini Alessia, Narzisi Antonio, Gesi Camilla, Carmassi Claudia, Dell'Osso Liliana, Cioni Giovanni, Muratori Filippo, Guzzetta Andrea
Institute of Clinical Physiology, National Research Council of Italy, 56124, Pisa, Italy.
IRCCS Stella Maris Foundation, 56128, Pisa, Italy.
J Clin Med. 2019 Apr 10;8(4):487. doi: 10.3390/jcm8040487.
Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders that is characterized by an altered brain connectivity organization. Autistic traits below the clinical threshold (i.e., the broad autism phenotype; BAP) are frequent among first-degree relatives of subjects with ASD; however, little is known regarding whether subthreshold behavioral manifestations of ASD mirror also at the neuroanatomical level in parents of ASD probands. To this aim, we applied advanced diffusion network analysis to MRI of 16 dyads consisting of a child with ASD and his father in order to investigate: (i) the correlation between structural network organization and autistic features in preschoolers with ASD (all males; age range 1.5-5.2 years); (ii) the correlation between structural network organization and BAP features in the fathers of individuals with ASD (fath-ASD). Local network measures significantly correlated with autism severity in ASD children and with BAP traits in fath-ASD, while no significant association emerged when considering the global measures of brain connectivity. Notably, an overlap of some brain regions that are crucial for social functioning (cingulum, superior temporal gyrus, inferior temporal gyrus, middle frontal gyrus, frontal pole, and amygdala) in patients with ASD and fath-ASD was detected, suggesting an intergenerational transmission of these neural substrates. Overall, the results of this study may help in elucidating the neurostructural endophenotype of ASD, paving the way for bridging connections between underlying genetic and ASD symptomatology.
自闭症谱系障碍（ASD）是一组神经发育障碍，其特征是大脑连接组织改变。在ASD患者的一级亲属中，低于临床阈值的自闭症特征（即广泛自闭症表型；BAP）很常见；然而，关于ASD先证者父母的亚阈值行为表现在神经解剖学水平上是否也有体现，我们知之甚少。为了实现这一目标，我们对由一名患有ASD的儿童及其父亲组成的16对亲子进行了MRI的高级扩散网络分析，以研究：（i）患有ASD的学龄前儿童（均为男性；年龄范围1.5 - 5.2岁）的结构网络组织与自闭症特征之间的相关性；（ii）ASD患者父亲（fath - ASD）的结构网络组织与BAP特征之间的相关性。局部网络测量值与ASD儿童的自闭症严重程度以及fath - ASD中的BAP特征显著相关，而在考虑大脑连接的全局测量值时未发现显著关联。值得注意的是，在ASD患者和fath - ASD中检测到一些对社交功能至关重要的脑区（扣带、颞上回、颞下回、额中回、额极和杏仁核）存在重叠，这表明这些神经基质存在代际传递。总体而言，本研究结果可能有助于阐明ASD的神经结构内表型，为连接潜在基因与ASD症状学之间的联系铺平道路。
