Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Transl Psychiatry. 2023 Feb 18;13(1):61. doi: 10.1038/s41398-023-02358-w.
The 15q11.2 BP1-BP2 copy number variant (CNV) is associated with altered brain morphology and risk for atypical development, including increased risk for schizophrenia and learning difficulties for the deletion. However, it is still unclear whether differences in brain morphology are associated with neurodevelopmental or neurodegenerative processes. This study derived morphological brain MRI measures in 15q11.2 BP1-BP2 deletion (n = 124) and duplication carriers (n = 142), and matched deletion-controls (n = 496) and duplication-controls (n = 568) from the UK Biobank study to investigate the association with brain morphology and estimates of brain ageing. Further, we examined the ageing trajectory of age-affected measures (i.e., cortical thickness, surface area, subcortical volume, reaction time, hand grip strength, lung function, and blood pressure) in 15q11.2 BP1-BP2 CNV carriers compared to non-carriers. In this ageing population, the results from the machine learning models showed that the estimated brain age gaps did not differ between the 15q11.2 BP1-BP2 CNV carriers and non-carriers, despite deletion carriers displaying thicker cortex and lower subcortical volume compared to the deletion-controls and duplication carriers, and lower surface area compared to the deletion-controls. Likewise, the 15q11.2 BP1-BP2 CNV carriers did not deviate from the ageing trajectory on any of the age-affected measures examined compared to non-carriers. Despite altered brain morphology in 15q11.2 BP1-BP2 CNV carriers, the results did not show any clear signs of apparent altered ageing in brain structure, nor in motor, lung or heart function. The results do not indicate neurodegenerative effects in 15q11.2 BP1-BP2 CNV carriers.
15q11.2BP1-BP2 拷贝数变异 (CNV) 与改变的大脑形态和发育异常的风险相关，包括删除后增加精神分裂症和学习困难的风险。然而，目前尚不清楚大脑形态的差异是否与神经发育或神经退行性过程有关。本研究从英国生物银行研究中得出了 15q11.2BP1-BP2 缺失（n=124）和重复携带者（n=142）的形态学脑 MRI 测量值，以及缺失对照（n=496）和重复对照（n=568），以研究与大脑形态的关联和大脑老化的估计值。此外，我们还检查了 15q11.2BP1-BP2CNV 携带者与非携带者相比，受年龄影响的测量指标（即皮质厚度、表面积、皮质下体积、反应时间、手握力、肺功能和血压）的老化轨迹。在这个老龄化人群中，机器学习模型的结果表明，尽管与缺失对照相比，缺失携带者的皮质更厚，皮质下体积更低，与缺失对照相比，表面面积更低，与非携带者相比，15q11.2BP1-BP2CNV 携带者的估计脑龄差距没有差异。同样，与非携带者相比，15q11.2BP1-BP2CNV 携带者在受年龄影响的任何测量指标上都没有偏离衰老轨迹。尽管 15q11.2BP1-BP2CNV 携带者的大脑形态发生了改变，但结果并未显示出任何明显的大脑结构老化或运动、肺或心脏功能改变的迹象。这些结果表明，15q11.2BP1-BP2CNV 携带者没有神经退行性效应。
