Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland.
Department of Clinical Neurosciences, Laboratory for Research in Neuroimaging LREN, Centre for Research in Neuroscience, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Transl Psychiatry. 2022 Aug 5;12(1):316. doi: 10.1038/s41398-022-02091-w.
Given controversial findings of reduced depressive symptom severity and increased hippocampus volume in CYP2C19 poor metabolizers, we sought to provide empirical evidence from a large-scale single-center longitudinal cohort in the community-dwelling adult population-Colaus|PsyCoLaus in Lausanne, Switzerland (n = 4152). We looked for CYP2C19 genotype-related behavioral and brain anatomy patterns using a comprehensive set of psychometry, water diffusion- and relaxometry-based magnetic resonance imaging (MRI) data (BrainLaus, n = 1187). Our statistical models tested for differential associations between poor metabolizer and other metabolizer status with imaging-derived indices of brain volume and tissue properties that explain individuals' current and lifetime mood characteristics. The observed association between CYP2C19 genotype and lifetime affective status showing higher functioning scores in poor metabolizers, was mainly driven by female participants (ß = 3.9, p = 0.010). There was no difference in total hippocampus volume between poor metabolizer and other metabolizer, though there was higher subiculum volume in the right hippocampus of poor metabolizers (ß = 0.03, p = 0.036). Our study supports the notion of association between mood phenotype and CYP2C19 genotype, however, finds no evidence for concomitant hippocampus volume differences, with the exception of the right subiculum.
鉴于 CYP2C19 弱代谢者的抑郁症状严重程度降低和海马体体积增加的争议性发现，我们试图从瑞士洛桑的社区居住成年人群体中的一项大规模单中心纵向队列研究（Colaus|PsyCoLaus，n=4152）中提供实证证据。我们使用一套全面的心理测量学、基于水扩散和弛豫率的磁共振成像 (MRI) 数据（BrainLaus，n=1187），寻找与 CYP2C19 基因型相关的行为和大脑解剖结构模式。我们的统计模型测试了弱代谢者和其他代谢者状态与大脑体积和组织特性的成像衍生指数之间的差异关联，这些指数可以解释个体当前和终身的情绪特征。观察到 CYP2C19 基因型与终身情感状态之间的关联，表明弱代谢者的功能评分更高，这主要是由女性参与者驱动的（ß=3.9，p=0.010）。弱代谢者和其他代谢者之间的总海马体体积没有差异，但弱代谢者的右侧海马体的下托体积更大（ß=0.03，p=0.036）。我们的研究支持情绪表型与 CYP2C19 基因型之间存在关联的观点，但没有发现海马体体积差异的证据，除了右侧下托。
