School of Medicine, National Taiwan University College of Medicine, and Department of Medical Education, National Taiwan University Hospital, Taipei (Tung); Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei (Tung, Lin, Shang, Gau); Azrieli Adult Neurodevelopmental Centre and Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto (Lin); Department of Psychiatry, University of Toronto, Toronto (Lin); Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei (Chen, Yang, Hsu, Tseng); Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei (Tseng, Gau); Molecular Imaging Center, National Taiwan University, Taipei (Tseng).
Am J Psychiatry. 2021 Aug 1;178(8):730-743. doi: 10.1176/appi.ajp.2020.20070999. Epub 2021 Mar 17.
The heterogeneity of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) preclude definitive identification of neurobiomarkers and biological risks. High clinical overlap suggests multifaceted circuit-level alterations across diagnoses, which remains elusive. This study investigated whether individuals with ADHD or ASD and their unaffected siblings constitute a spectrum of neurodevelopmental conditions in terms of white matter etiology.
Sex-specific white matter tract normative development was modeled from diffusion MRI of 626 typically developing control subjects (ages 5-40 years; 376 of them male). Individualized metrics estimating white matter tract deviation from the age norm were derived for 279 probands with ADHD, 175 probands with ASD, and their unaffected siblings (ADHD, N=121; ASD, N=72).
ASD and ADHD shared diffuse white matter tract deviations in the commissure and association tracts (rho=0.54; p<0.001), while prefrontal corpus callosum deviated more remarkably in ASD (effect size=-0.36; p<0.001). Highly correlated deviance patterns between probands and unaffected siblings were found in both ASD (rho=0.69; p<0.001) and ADHD (rho=0.51; p<0.001), but only unaffected sisters of ASD probands showed a potential endophenotype in long-range association fibers and projection fibers connecting prefrontal regions. ADHD and ASD shared significant white matter tract idiosyncrasy (rho=0.55; p<0.001), particularly in tracts connecting prefrontal regions, not identified in either sibling group. Canonical correlation analysis identified multiple dimensions of psychopathology/cognition across categorical entities; autistic, visual memory, intelligence/planning/inhibition, nonverbal-intelligence/attention, working memory/attention, and set-shifting/response-variability were associated with distinct sets of white matter tract deviations.
When conceptualizing neurodevelopmental disorders as white matter tract deviations from normative patterns, ASD and ADHD are more alike than different. The modest white matter tract alterations in siblings suggest potential endophenotypes in these at-risk populations. This study further delineates brain-driven dimensions of psychopathology/cognition, which may help clarify within-diagnosis heterogeneity and high between-diagnosis co-occurrence.
自闭症谱系障碍 (ASD) 和注意缺陷多动障碍 (ADHD) 的异质性排除了神经生物标志物和生物学风险的明确鉴定。高临床重叠表明跨诊断存在多方面的回路水平改变，但仍难以捉摸。本研究调查了 ADHD 或 ASD 患者及其未受影响的兄弟姐妹是否构成神经发育状况的谱系，从弥散 MRI 研究了 626 名正常发育的对照者（年龄 5-40 岁；其中 376 名为男性）。为 279 名 ADHD 患者、175 名 ASD 患者及其未受影响的兄弟姐妹（ADHD，N=121；ASD，N=72）个体计算了估计白质束偏离年龄规范的个体指标。
从 626 名正常发育的对照者（年龄 5-40 岁；其中 376 名为男性）的弥散 MRI 中对性别特异性白质束正常发育进行建模。为 279 名 ADHD 患者、175 名 ASD 患者及其未受影响的兄弟姐妹（ADHD，N=121；ASD，N=72）计算了估计白质束偏离年龄规范的个体指标。
ASD 和 ADHD 在联合和联合束中存在弥漫性白质束偏差（rho=0.54；p<0.001），而 ASD 中前额叶胼胝体的偏差更为明显（效应量=-0.36；p<0.001）。在 ASD（rho=0.69；p<0.001）和 ADHD（rho=0.51；p<0.001）中，均发现 ASD 患者及其未受影响的兄弟姐妹之间存在高度相关的偏差模式，但仅 ASD 患者的未受影响的姐妹在连接前额叶区域的长程联合纤维和投射纤维中显示出潜在的表型。ADHD 和 ASD 共享显著的白质束特质（rho=0.55；p<0.001），特别是在前额叶区域连接的束中，在任何一个兄弟姐妹组中都没有发现。典型相关分析确定了分类实体之间的多个精神病理学/认知维度；自闭症、视觉记忆、智力/计划/抑制、非语言智力/注意力、工作记忆/注意力和转换/反应变异性与不同的白质束偏差集相关。
当将神经发育障碍概念化为白质束偏离正常模式时，ASD 和 ADHD 比不同更相似。兄弟姐妹中轻微的白质束改变表明这些高危人群中存在潜在的表型。本研究进一步描述了与精神病理学/认知相关的大脑驱动维度，这可能有助于阐明诊断内异质性和高诊断间共病性。
