Pharmacogenetic studies have shown involvement of cytochrome P450 enzymes in the metabolism of psychotropic drugs. However, expression and activity on endogenous substrates in the brain may underlie a constitutive role of these enzymes beyond drug metabolism. CYP2C19, which is expressed in the human fetal brain during neurodevelopment, shows affinity for endogenous compounds including monoaminergic neurotransmitters, steroid hormones, and endocannabinoids. In this study (N = 608), we looked at the genetic polymorphism of CYP2C19 and its potential associations with structural phenotypes of subcortical brain volume with structural imaging. Using two independent volume estimation techniques, we found converging evidence for a positive association between CYP2C19 activity scores, as inferred from the genotype, and basal ganglia and hippocampal volume. This association was present only in female individuals, raising the possibility that effects on brain morphology may arise through a mechanism involving the metabolism of estrogen steroids.

药物遗传学研究表明，细胞色素 P450 酶参与了精神药物的代谢。然而，大脑内源性底物的表达和活性可能是这些酶在药物代谢之外的组成性作用的基础。CYP2C19 在神经发育过程中在人类胎儿大脑中表达，对包括单胺能神经递质、类固醇激素和内源性大麻素在内的内源性化合物具有亲和力。在这项研究 ( N  = 608) 中，我们通过结构成像研究了 CYP2C19 的遗传多态性及其与皮质下脑容量结构表型的潜在关联。使用两种独立的体积估计技术，我们发现了CYP2C19之间正相关的趋同证据从基因型、基底神经节和海马体积推断出的活动评分。这种关联只存在于女性个体中，这增加了对大脑形态的影响可能通过涉及雌激素类固醇代谢的机制产生的可能性。