Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Feb;9(2):156-163. doi: 10.1016/j.bpsc.2023.09.001. Epub 2023 Sep 12.
The 22q11.2 deletion syndrome (22qDel) is a genetic copy number variant that strongly increases risk for schizophrenia and other neurodevelopmental disorders. Disrupted functional connectivity between the thalamus and the somatomotor/frontoparietal cortex has been implicated in cross-sectional studies of 22qDel, idiopathic schizophrenia, and youths at clinical high risk for psychosis. Here, we used a novel functional atlas approach to investigate longitudinal age-related changes in network-specific thalamocortical functional connectivity (TCC) in participants with 22qDel and typically developing (TD) control participants.
TCC was calculated for 9 functional networks derived from resting-state functional magnetic resonance imaging scans collected from 65 participants with 22qDel (63.1% female) and 69 demographically matched TD control participants (49.3% female) ages 6 to 23 years. Analyses included 86 longitudinal follow-up scans. Nonlinear age trajectories were characterized with generalized additive mixed models.
In participants with 22qDel, TCC in the frontoparietal network increased until approximately age 13, while somatomotor TCC and cingulo-opercular TCC decreased from age 6 to 23. In contrast, no significant relationships between TCC and age were found in TD control participants. Somatomotor connectivity was significantly higher in participants with 22qDel than in TD control participants in childhood, but lower in late adolescence. Frontoparietal TCC showed the opposite pattern.
22qDel is associated with aberrant development of functional network connectivity between the thalamus and cortex. Younger individuals with 22qDel have lower frontoparietal connectivity and higher somatomotor connectivity than control individuals, but this phenotype may normalize or partially reverse by early adulthood. Altered maturation of this circuitry may underlie elevated neuropsychiatric disease risk in this syndrome.
22q11.2 缺失综合征（22qDel）是一种遗传拷贝数变异，强烈增加了精神分裂症和其他神经发育障碍的风险。丘脑与躯体运动/额顶叶皮层之间功能连接的中断已在 22qDel、特发性精神分裂症和处于精神病临床高风险的青少年的横断面研究中被牵连。在这里，我们使用一种新的功能图谱方法来研究 22qDel 患者和典型发育（TD）对照组参与者中网络特异性丘脑皮质功能连接（TCC）的纵向年龄相关变化。
从 65 名 22qDel 患者（63.1%女性）和 69 名在人口统计学上匹配的 TD 对照组参与者（49.3%女性）的静息状态功能磁共振成像扫描中计算 TCC。参与者年龄在 6 至 23 岁之间。分析包括 86 次纵向随访扫描。使用广义加性混合模型来描述非线性年龄轨迹。
在 22qDel 患者中，额顶叶网络的 TCC 增加，直到大约 13 岁，而躯体运动 TCC 和扣带回-顶叶网络的 TCC 从 6 岁到 23 岁减少。相比之下，TD 对照组参与者的 TCC 与年龄之间没有显著关系。在童年时期，22qDel 患者的躯体运动连接明显高于 TD 对照组参与者，但在青春期晚期较低。额顶叶 TCC 则呈现相反的模式。
22qDel 与丘脑和皮层之间功能网络连接的异常发育有关。患有 22qDel 的年轻个体的额顶叶连接较低，躯体运动连接较高，而对照个体的连接较高，但这种表型可能在成年早期正常化或部分逆转。该电路的改变成熟可能是该综合征中神经精神疾病风险升高的基础。
