Pecci-Terroba Clara, Lai Meng-Chuan, Lombardo Michael V, Chakrabarti Bhismadev, Ruigrok Amber N V, Suckling John, Anagnostou Evdokia, Lerch Jason P, Taylor Margot J, Nicolson Rob, Georgiades Stelios, Crosbie Jennifer, Schachar Russell, Kelley Elizabeth, Jones Jessica, Arnold Paul D, Seidlitz Jakob, Alexander-Bloch Aaron F, Bullmore Edward T, Baron-Cohen Simon, Bedford Saashi A, Bethlehem Richard A I
Department of Psychology, University of Cambridge, Cambridge, UK.
Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
Mol Autism. 2025 Jun 4;16(1):33. doi: 10.1186/s13229-025-00667-z.
Autism and attention deficit hyperactivity disorder (ADHD) are two highly heterogeneous neurodevelopmental conditions with variable underlying neurobiology. Imaging studies have yielded varied results, and it is now clear that there is unlikely to be one characteristic neuroanatomical profile of either condition. Parsing this heterogeneity could allow us to identify more homogeneous subgroups, either within or across conditions, which may be more clinically informative. This has been a pivotal goal for neurodevelopmental research using both clinical and neuroanatomical features, though results thus far have again been inconsistent with regards to the number and characteristics of subgroups.
Here, we use population modelling to cluster a multi-site dataset based on global and regional centile scores of cortical thickness, surface area and grey matter volume. We use HYDRA, a novel semi-supervised machine learning algorithm which clusters based on differences to controls and compare its performance to a traditional clustering approach.
We identified distinct subgroups within autism and ADHD, as well as across diagnosis, often with opposite neuroanatomical alterations relatively to controls. These subgroups were characterised by different combinations of increased or decreased patterns of morphometrics. We did not find significant clinical differences across subgroups.
Crucially, however, the number of subgroups and their membership differed vastly depending on chosen features and the algorithm used, highlighting the impact and importance of careful method selection.
We highlight the importance of examining heterogeneity in autism and ADHD and demonstrate that population modelling is a useful tool to study subgrouping in autism and ADHD. We identified subgroups with distinct patterns of alterations relative to controls but note that these results rely heavily on the algorithm used and encourage detailed reporting of methods and features used in future studies.
自闭症和注意力缺陷多动障碍(ADHD)是两种高度异质性的神经发育疾病,其潜在神经生物学各不相同。影像学研究结果各异,现在很清楚,这两种疾病不太可能存在单一特征性的神经解剖学特征。剖析这种异质性可以使我们识别出在疾病内部或跨疾病的更同质亚组,这可能在临床上更具指导意义。这一直是利用临床和神经解剖学特征进行神经发育研究的关键目标,尽管迄今为止关于亚组的数量和特征的结果再次不一致。
在这里,我们使用人群建模方法,根据皮质厚度、表面积和灰质体积的全局和区域百分位数分数对一个多站点数据集进行聚类。我们使用一种新颖的半监督机器学习算法HYDRA,该算法基于与对照组的差异进行聚类,并将其性能与传统聚类方法进行比较。
我们在自闭症和ADHD内部以及跨诊断识别出了不同的亚组,相对于对照组,这些亚组通常具有相反的神经解剖学改变。这些亚组的特征是形态测量学增加或减少模式的不同组合。我们没有发现亚组之间存在显著的临床差异。
然而,至关重要的是,亚组的数量及其成员组成因所选特征和使用的算法而有很大差异,这突出了仔细选择方法的影响和重要性。
我们强调了研究自闭症和ADHD异质性的重要性,并证明人群建模是研究自闭症和ADHD亚组划分的有用工具。我们识别出了相对于对照组具有不同改变模式的亚组,但请注意,这些结果严重依赖于所使用的算法,并鼓励在未来研究中详细报告所使用的方法和特征。