探讨孤独症中重复和限制性行为和兴趣的多维本质：神经解剖学关联和临床意义

作者：

Aline Lefebvre, Nicolas Traut, Amandine Pedoux, Anna Maruani, Anita Beggiato, Monique Elmaleh, David Germanaud, Anouck Amestoy, Myriam Ly‑Le Moal, Christopher Chatham, Lorraine Murtagh, Manuel Bouvard, Marianne Alisson, Marion Leboyer, Thomas Bourgeron, Roberto Toro, Guillaume Dumas, Clara Moreau and Richard Delorme

摘要：

Background： Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into ‘motor‑driven’ and ‘cognitively driven’. RRBI symptomatology depends on the individual’s clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures—involving cortical and subcortical areas.

Method： A sample of 792 individuals composed of 267 autistic subjects, their 370 first‑degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale‑Revised and the Yale‑Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n = 152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI‑derived factors with brain volumes using linear regression models.

Results ：We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the ‘motor‑driven’ RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y‑BOCS related items and represented the ‘cognitively driven’ RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p < 0.05). FA1 was negatively associated with the left amygdala (uncorrected p < 0.05), and FA2 was positively associated with the left parietal structure (uncorrected p = 0.001).

背景：重复受限的行为和兴趣( RRBI )是自闭症的核心症状，是一个复杂的整体，通常分为”运动驱动”和”认知驱动”。RRBI的症状学取决于个体的临床环境，限制了对RRBI生理学，特别是其相关的神经解剖结构的理解。复杂的RRBI异质性需要通过整合临床背景[自闭症个体及其亲属和典型发育( TD )个体来探索整个RRBI谱系。我们假设，通过探索RRBI的整个频谱，会出现不同的RRBI维度，并且这些维度与神经解剖学特征相关- -涉及皮层和皮层下区域。

方法：本研究共招募了792名被试，包括267名自闭症被试及其370名一级亲属和155名TD被试。我们使用重复行为量表( Repetitive Behavior Scale‐Revised )和耶鲁-布朗强迫量表( Yale‐Brown Obsessive Compulsive Scale )评估每个个体的RRBI整体模式。我们使用MRI扫描仪对受试者( n = 152 , ASD42例,亲属89例, TD13例)的子样本进行了脑体积估计。我们首先通过对这些量表的所有项目进行主成分分析来调查RRBI的维度，并将所有抽样人群包括在内。然后，我们使用线性回归模型探讨了RRBI衍生因子与大脑体积之间的关系。

结论：我们确定了3个主要因子(具有30.3 %的RRBI累积方差)：因子1 ( FA1为12.7 %)主要反映”运动驱动型” RRBI症状；因子2和3 ( 8 %和7 . 9 %)主要聚集了Y‐BOCS相关条目，代表了”认知驱动”的RRBI症状。这3个因子与右壳核/左壳核体积显著相关，但作用相反：FA1与右壳核/左壳核体积增加呈负相关，FA2和FA3与(所有未校正p < 0.05)呈负相关。FA1与左侧杏仁核(未校正p < 0.05)呈负相关，FA2与左侧顶叶结构(未校正p = 0.001)呈正相关。