Lin Bochao Danae, Li Yunzhi, Goula Anastasia A, Chang Xiao, Grasby Katrina L, Medland Sarah, Andreassen Ole A, Rutten Bart P F, Guloksuz Sinan, van der Meer Dennis, Luykx Jurjen J
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng, China.
Nat Ment Health. 2025 Jun;3(6):613-625. doi: 10.1038/s44220-025-00397-4. Epub 2025 May 19.
Brain cortical morphology, indexed by its surface area and thickness, is known to be highly heritable. Previous research has suggested a relationship of cortical morphology with several neuropsychiatric phenotypes. However, the multitude of potential confounders makes it difficult to establish causal relationships. Here, we employ Generalized Summary-data-based Mendelian Randomization and a series of sensitivity analyses to investigate causal links between 70 cortical morphology measures and 199 neuropsychiatric, behavioral, and metabolic phenotypes. We show that total brain cortical surface area (TSA) has significant positive causal effects on 18 phenotypes. The strongest effects include TSA positively influencing cognitive performance, while reverse analyses reveal small effects of cognitive performance on TSA. Global mean cortical thickness (MTH) exhibits significant causal effects on five phenotypes, including schizophrenia. MTH reduces schizophrenia risk and bidirectional causality is found between MTH and smoking initiation. Finally, in regional analyses we detect positive influences of the transverse temporal surface area on cognitive performance and negative influences of transverse temporal thickness on schizophrenia risk. Overall, our results highlight bidirectional associations between TSA, MTH, and neuropsychiatric traits. These insights offer potential avenues for intervention studies aimed at improving brain health.
以表面积和厚度为指标的大脑皮质形态学,已知具有高度遗传性。先前的研究表明皮质形态学与几种神经精神疾病表型之间存在关联。然而,众多潜在的混杂因素使得难以建立因果关系。在此,我们采用基于广义汇总数据的孟德尔随机化方法及一系列敏感性分析,来研究70种皮质形态学指标与199种神经精神、行为和代谢表型之间的因果联系。我们发现,全脑皮质表面积(TSA)对18种表型具有显著的正向因果效应。最强的效应包括TSA对认知能力有正向影响,而反向分析显示认知能力对TSA的影响较小。全球平均皮质厚度(MTH)对包括精神分裂症在内的5种表型具有显著的因果效应。MTH降低精神分裂症风险,并且在MTH与开始吸烟之间发现了双向因果关系。最后,在区域分析中,我们检测到颞横回表面积对认知能力有正向影响,而颞横回厚度对精神分裂症风险有负向影响。总体而言,我们的结果突出了TSA、MTH与神经精神特质之间的双向关联。这些见解为旨在改善大脑健康的干预研究提供了潜在途径。
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