Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
Cardiff University's Brain Research Imaging Centre (CUBRIC), School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK.
Neuropsychopharmacology. 2024 Jan;49(2):368-376. doi: 10.1038/s41386-023-01628-x. Epub 2023 Jul 4.
Although many genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. In this study, magnetoencephalography (MEG) was used to investigate electrophysiological markers of local and global network function in 34 children with 22q11.2DS and 25 controls aged 10-17 years old. Resting-state oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, neurodevelopmental symptoms and IQ. Children with 22q11.2DS had altered network activity and connectivity in high and low frequency bands, reflecting modified local and long-range cortical circuitry. Alpha and theta band connectivity were negatively associated with ASD symptoms while frontal high frequency (gamma band) activity was positively associated with ASD symptoms. Alpha band activity was positively associated with cognitive ability. These findings suggest that haploinsufficiency at the 22q11.2 locus impacts short and long-range cortical circuits, which could be a mechanism underlying neurodevelopmental and psychiatric vulnerability in this high-risk group.
尽管已经确定了许多精神疾病和神经发育障碍的遗传风险因素，但从遗传风险到神经精神结果的神经生物学途径仍不清楚。22q11.2 缺失综合征（22q11.2DS）是一种拷贝数变异（CNV）综合征，与神经发育和精神障碍的高发病率相关，包括自闭症谱系障碍（ASD）、注意缺陷多动障碍（ADHD）和精神分裂症。神经整合和皮质连接的改变与 22q11.2DS 中所见的一系列神经精神障碍有关，并且可能是 CNV 增加风险的机制。在这项研究中，使用脑磁图（MEG）研究了 34 名患有 22q11.2DS 的儿童和 25 名年龄在 10-17 岁的对照者的局部和全局网络功能的电生理标志物。比较了两组之间的静息状态振荡活动和六个频带的功能连接。回归分析用于探索这些测量值、神经发育症状和智商之间的关系。患有 22q11.2DS 的儿童在高和低频率带中具有改变的网络活动和连接性，反映出皮质电路的局部和长程改变。α 和θ频段的连接与 ASD 症状呈负相关，而额部高频（γ 频段）活动与 ASD 症状呈正相关。α 频段活动与认知能力呈正相关。这些发现表明，22q11.2 基因座的杂合不足会影响短程和长程皮质回路，这可能是该高风险组神经发育和精神易感性的机制。
