Institute of Mental Health, Jining Medical University, 16 Hehua Rd, Taibaihu New District, Jining, 272067, Shandong, China.
Department of Psychiatry, Jining Medical University, 16 Hehua Rd, Taibaihu New District, Jining, 272067, Shandong, China.
Eur Arch Psychiatry Clin Neurosci. 2020 Jun;270(4):443-449. doi: 10.1007/s00406-019-00985-3. Epub 2019 Jan 31.
Cognitive impairment is one of the core symptoms of schizophrenia. Multiple domains of cognition are affected in patients with schizophrenia, which has a major effect on the functional outcome. Recent studies indicate that SNPs in the gamma-aminobutyric acid type A receptor beta 2 subunit (GABRB2) gene are associated with the risk of schizophrenia, however, the effect of these SNPs on cognitive function in patients with schizophrenia has not been explored. In this study, we first performed a case-control analysis of three SNPs (rs187269 allele A vs. G, rs252944 allele C vs. G, and rs194072 allele A vs. G) in 100 patients and 90 controls, then conducted a meta-analysis and found the SNP rs194072 was associated with schizophrenia (OR = 0.86, P = 0.0119), and survived after Bonferroni correction. The haplotype analysis suggested that the haplotype ACA, comprising the three SNPs (rs187269, rs252944 and rs194072) was also significantly associated with schizophrenia (P = 0.049).Then, we performed an association analysis of three SNPs (rs187269, rs252944 and rs194072) in GABRB2 gene with cognitive performance in patients with first episode schizophrenia. We found that the allele G of rs187269 in the GABRB2 gene was significantly associated with better cognitive flexibility (P = 0.005), a major aspect of executive function, in patients with first episode schizophrenia. The haplotype ACA was significantly associated with cognitive flexibility in patients with schizophrenia (P = 0.023). Our study showed that SNPs in GABRB2 may have a significant effect on cognitive function in patients with schizophrenia, suggesting that modulating GABRB2 may have therapeutic potential to improve cognitive function of patients with schizophrenia.
认知障碍是精神分裂症的核心症状之一。精神分裂症患者的多个认知领域受到影响,这对其功能结果有重大影响。最近的研究表明,γ-氨基丁酸 A 型受体β 2 亚基(GABRB2)基因中的 SNP 与精神分裂症的风险相关,然而,这些 SNP 对精神分裂症患者认知功能的影响尚未得到探索。在这项研究中,我们首先对 100 例患者和 90 例对照进行了三个 SNP(rs187269 等位基因 A 与 G、rs252944 等位基因 C 与 G 和 rs194072 等位基因 A 与 G)的病例对照分析,然后进行了荟萃分析,发现 SNP rs194072 与精神分裂症相关(OR=0.86,P=0.0119),并且在经过 Bonferroni 校正后仍然存在。单体型分析表明,由三个 SNP(rs187269、rs252944 和 rs194072)组成的单体型 ACA 也与精神分裂症显著相关(P=0.049)。然后,我们在首发精神分裂症患者中进行了 GABRB2 基因中三个 SNP(rs187269、rs252944 和 rs194072)与认知表现的关联分析。我们发现,GABRB2 基因中的 rs187269 等位基因 G 与首发精神分裂症患者认知灵活性(执行功能的主要方面)显著相关(P=0.005)。单体型 ACA 与精神分裂症患者的认知灵活性显著相关(P=0.023)。我们的研究表明,GABRB2 中的 SNP 可能对精神分裂症患者的认知功能有显著影响,这表明调节 GABRB2 可能具有改善精神分裂症患者认知功能的治疗潜力。