Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD + ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD—but not for ADHD-related genes. Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N = 25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression.

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自闭症和多动症的神经解剖学基础及其与假定的基因组基础的联系

自闭症谱系障碍 (ASD) 是一种伴有大脑发育差异的神经发育疾病。自闭症的神经解剖学差异在个体之间存在差异，并且可能支撑不同的临床表型。为了解析异质性，有必要确定自闭症谱系障碍的神经生物学如何受到与同时发生的疾病（例如注意力缺陷/多动障碍（ADHD））相关的差异的调节。本研究的目的是（1）调查患有和不患有多动症的自闭症个体的组间差异，以及（2）将这些差异与假定的基因组基础联系起来。我们检查了来自欧洲纵向自闭症项目的 533 名个体样本中皮质厚度 (CT) 和表面积 (SA) 的差异及其基因组关联。使用包括自闭症和 ADHD 的主要影响以及 ASD 与 ADHD 相互作用的一般线性模型，我们检查了 ADHD 在多大程度上调节自闭症相关的神经解剖学。此外，利用艾伦人脑图谱的空间基因表达数据，我们确定了其空间表达模式与我们的神经影像学发现相似的基因。除了额颞叶、边缘和枕叶区域 ASD 和 ADHD 的显着主效应外，我们还分别在 CT 和 SA 测量中观察到左侧中央前回和右侧额回显着的 ASD 与 ADHD 相互作用。此外，患有自闭症谱系障碍 (ASD) + 多动症 (ADHD) 的个体在 CT 上的表现与非自闭症谱系障碍 (ASD) + 多动症 (ADHD) 的个体不同。ASD 的主效应和相互作用都得到了丰富，但 ADHD 相关基因却没有。尽管我们采用多中心设计来克服单中心招募限制，但与其他亚组相比，仅 ADHD 组中 N = 25 人的样本量相对较小，这限制了结果的普遍性。此外，我们根据 DSM-5 评分量表将受试者分为 ADHD 阳性分组。虽然这足以获得多动症的研究诊断，但我们的方法没有考虑症状出现的时间，而这通常是在临床环境中评估多动症时考虑的。因此，我们的研究结果表明，自闭症谱系障碍的神经解剖学受到 ADHD 的显着调节，并且同时患有 ADHD 的自闭症个体可能具有由非典型基因表达介导的特定神经解剖学基础。