Levitis Elizabeth, Liu Siyuan, Whitman Ethan T, Warling Allysa, Torres Erin, Clasen Liv S, Lalonde François M, Sarlls Joelle, Alexander Daniel C, Raznahan Armin
Section on Developmental Neurogenomics, National Institute of Mental Health, Bethesda, Maryland; Center for Medical Image Computing, Department of Computer Science, UCL, London, UK.
Section on Developmental Neurogenomics, National Institute of Mental Health, Bethesda, Maryland.
Biol Psychiatry. 2024 Jan 15;95(2):136-146. doi: 10.1016/j.biopsych.2023.07.008. Epub 2023 Jul 20.
Diverse gene dosage disorders (GDDs) increase risk for psychiatric impairment, but characterization of GDD effects on the human brain has so far been piecemeal, with few simultaneous analyses of multiple brain features across different GDDs.
Here, through multimodal neuroimaging of 3 aneuploidy syndromes (XXY [total n = 191, 92 control participants], XYY [total n = 81, 47 control participants], and trisomy 21 [total n = 69, 41 control participants]), we systematically mapped the effects of supernumerary X, Y, and chromosome 21 dosage across a breadth of 15 different macrostructural, microstructural, and functional imaging-derived phenotypes (IDPs).
The results revealed considerable diversity in cortical changes across GDDs and IDPs. This variegation of IDP change underlines the limitations of studying GDD effects unimodally. Integration across all IDP change maps revealed highly distinct architectures of cortical change in each GDD along with partial coalescence onto a common spatial axis of cortical vulnerability that is evident in all 3 GDDs. This common axis shows strong alignment with shared cortical changes in behaviorally defined psychiatric disorders and is enriched for specific molecular and cellular signatures.
Use of multimodal neuroimaging data in 3 aneuploidies indicates that different GDDs impose unique fingerprints of change in the human brain that differ widely depending on the imaging modality that is being considered. Embedded in this variegation is a spatial axis of shared multimodal change that aligns with shared brain changes across psychiatric disorders and therefore represents a major high-priority target for future translational research in neuroscience.
多种基因剂量紊乱（GDDs）会增加精神障碍的风险，但迄今为止，GDDs对人类大脑影响的特征描述还很零散，很少对不同GDDs的多种脑特征进行同步分析。
在此，通过对3种非整倍体综合征（XXY[共191例，92例对照参与者]、XYY[共81例，47例对照参与者]和21三体综合征[共69例，41例对照参与者]）进行多模态神经成像，我们系统地绘制了额外的X、Y和21号染色体剂量对15种不同的宏观结构、微观结构和功能成像衍生表型（IDPs）的影响。
结果显示，不同GDDs和IDPs的皮质变化存在很大差异。IDP变化的这种多样性突显了单模态研究GDDs效应的局限性。整合所有IDP变化图显示，每种GDD的皮质变化结构高度不同，同时部分合并到一个共同的皮质易损性空间轴上，这在所有3种GDD中都很明显。这个共同轴与行为定义的精神障碍中共享的皮质变化高度一致，并富含特定的分子和细胞特征。
对3种非整倍体使用多模态神经成像数据表明，不同的GDDs在人脑中施加了独特的变化指纹，这取决于所考虑的成像方式而有很大差异。在这种多样性中嵌入了一个共享多模态变化的空间轴，它与精神障碍中共享的脑变化一致，因此代表了未来神经科学转化研究的一个主要高优先级目标。
