Probing naturally-occurring, reciprocal genomic copy number variations (CNVs) may help us understand mechanisms that underlie deviations from typical brain development. Cross-sectional studies have identified prominent reductions in cortical surface area (SA) and increased cortical thickness (CT) in 22q11.2 deletion carriers (22qDel), with the opposite pattern in duplication carriers (22qDup), but the longitudinal trajectories of these anomalies—and their relationship to clinical symptomatology—are unknown. Here, we examined neuroanatomic changes within a longitudinal cohort of 261 22q11.2 CNV carriers and demographically-matched typically developing (TD) controls (84 22qDel, 34 22qDup, and 143 TD; mean age 18.35, ±10.67 years; 50.47% female). A total of 431 magnetic resonance imaging scans (164 22qDel, 59 22qDup, and 208 TD control scans; mean interscan interval = 20.27 months) were examined. Longitudinal FreeSurfer analysis pipelines were used to parcellate the cortex and calculate average CT and SA for each region. First, general additive mixed models (GAMMs) were used to identify regions with between-group differences in developmental trajectories. Secondly, we investigated whether these trajectories were associated with clinical outcomes. Developmental trajectories of CT were more protracted in 22qDel relative to TD and 22qDup. 22qDup failed to show normative age-related SA decreases. 22qDel individuals with psychosis spectrum symptoms showed two distinct periods of altered CT trajectories relative to 22qDel without psychotic symptoms. In contrast, 22q11.2 CNV carriers with autism spectrum diagnoses showed early alterations in SA trajectories. Collectively, these results provide new insights into altered neurodevelopment in 22q11.2 CNV carriers, which may shed light on neural mechanisms underlying distinct clinical outcomes.

探索自然发生的相互基因组拷贝数变异（CNV）可能有助于我们了解典型大脑发育偏差的机制。横断面研究发现，22q11.2 缺失携带者 (22qDel) 的皮质表面积 (SA) 显着减少，皮质厚度 (CT) 增加，而重复携带者 (22qDup) 的模式相反，但这些异常的纵向轨迹——以及它们与临床症状学的关系——尚不清楚。在这里，我们检查了 261 名 22q11.2 CNV 携带者和人口统计学匹配的典型发育 (TD) 对照的纵向队列中的神经解剖学变化（84 22qDel、34 22qDup 和 143 TD；平均年龄 18.35，±10.67 岁；50.47% 女性） 。总共检查了 431 次磁共振成像扫描（164 次 22qDel、59 次 22qDup 和 208 次 TD 对照扫描；平均扫描间隔 = 20.27 个月）。纵向 FreeSurfer 分析管道用于对皮质进行分区并计算每个区域的平均 CT 和 SA。首先，使用一般加性混合模型（GAMM）来识别发育轨迹中具有组间差异的区域。其次，我们研究了这些轨迹是否与临床结果相关。相对于 TD 和 22qDup，22qDel 的 CT 发育轨迹更为延长。 22qDup 未能显示与年龄相关的标准 SA 下降。与没有精神病症状的 22qDel 个体相比，具有精神病谱系症状的 22qDel 个体表现出两个不同时期的 CT 轨迹改变。相比之下，患有自闭症谱系诊断的 22q11.2 CNV 携带者表现出 SA 轨迹的早期改变。总的来说，这些结果为 22q11 神经发育的改变提供了新的见解。2 CNV 携带者，这可能有助于揭示不同临床结果背后的神经机制。