Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou 510170, China.
Schizophr Res. 2018 Sep;199:214-220. doi: 10.1016/j.schres.2018.04.023. Epub 2018 May 3.
Dopamine in the prefrontal cortex (PFC) plays an important role in cognitive performance and regulates by catechol-O-methyltransferase (COMT) expression. To clarify the effect of COMT genotype on cognitive function in patients with schizophrenia, we performed DNA genotyping, cognitive evaluations, and functional magnetic resonance imaging (fMRI) in antipsychotic-naïve patients with first-episode schizophrenia (FES) and matched healthy control subjects. We found that all cognitive domains were impaired in patients with FES compared with healthy subjects. Moreover, COMT genotype influenced the verbal learning performance in healthy subjects, but not in patients with FES. Resting-state fMRI data revealed that patients with FES exhibited higher functional connectivity degree centrality in the medial PFC and lower degree centrality in the parietal-occipital junction than healthy subjects. Furthermore, patients with FES who were COMT Met allele carriers had higher degree centrality in the medial PFC than those with the Val/Val genotype. In contrast, in healthy controls, Met allele carriers exhibited higher degree centrality than healthy controls with the Val/Val genotype in the left hippocampus and left amygdala. There was a negative correlation between the degree centrality value in medial PFC and score of the Hopkins Verbal Learning Test-Revised (HVLT-R) in FES patients with the Met allele. Our findings suggest that COMT genotype differentially influences pathways related to cognitive performance in patients with FES versus healthy individuals, providing an important insight into schizophrenia pathophysiology.
前额叶皮层（PFC）中的多巴胺在认知表现中发挥重要作用，并通过儿茶酚-O-甲基转移酶（COMT）表达进行调节。为了阐明 COMT 基因型对首发精神分裂症（FES）患者认知功能的影响，我们对未经抗精神病药物治疗的 FES 患者和匹配的健康对照进行了 DNA 基因分型、认知评估和功能磁共振成像（fMRI）。我们发现，与健康受试者相比，所有认知领域均在 FES 患者中受损。此外，COMT 基因型影响健康受试者的言语学习表现，但不影响 FES 患者。静息状态 fMRI 数据显示，与健康受试者相比，FES 患者内侧前额叶的功能连接度中心性较高，顶枕叶交界处的度中心性较低。此外，FES 患者中 COMT Met 等位基因携带者的内侧前额叶的度中心性高于 Val/Val 基因型的患者。相比之下，在健康对照组中，Met 等位基因携带者的左侧海马体和左侧杏仁核的度中心性高于 Val/Val 基因型的健康对照组。FES 患者中 Met 等位基因携带者的内侧前额叶的度中心性值与霍普金斯言语学习测试修订版（HVLT-R）的分数呈负相关。我们的研究结果表明，COMT 基因型在 FES 患者和健康个体的认知表现相关通路中存在差异，为精神分裂症的病理生理学提供了重要的见解。
