Clinical Pharmacy Department, University of Michigan College of Pharmacy, Ann Arbor, Michigan.
Psychology Department, University of Michigan College of Literature, Science, and the Arts, Ann Arbor, Michigan.
Pharmacotherapy. 2017 Sep;37(9):1122-1130. doi: 10.1002/phar.1968. Epub 2017 Aug 2.
The authors sought to examine the impact of multiple risk alleles for cognitive dysfunction and cardiovascular disease risk on cognitive function and to determine if these relationships varied by cognitive reserve (CR) or concomitant medication use in patients with schizophrenia. They conducted a cross-sectional study in ambulatory mental health centers. A total of 122 adults with a schizophrenia spectrum diagnosis who were maintained on a stable antipsychotic regimen for at least 6 months before study enrollment were included. Patients were divided into three CR groups based on years of formal education: no high school completion or equivalent (low-education group [18 patients]), completion of high school or equivalent (moderate-education group [36 patients], or any degree of post-high school education (high-education group [68 patients]). The following pharmacogenomic variants were genotyped for each patient: AGT M268T (rs699), ACE insertion/deletion (or ACE I/D, rs1799752), and APOE ε2, ε3, and ε4 (rs429358 and rs7412). Risk allele carrier status (identified per gene as AGT M268 T carriers, ACE D carriers, and APOE ε4 carriers) was not significantly different among CR groups. The Brief Assessment of Cognition in Schizophrenia (BACS) scale was used to assess cognitive function. The mean ± SD patient age was 43.9 ± 11.6 years. Cardiovascular risk factors such as hypertension and hyperlipidemia diagnoses, and use of antihypertensive and lipid-lowering agents, did not significantly differ among CR groups. Mixed modeling revealed that risk allele carrier status was significantly associated with lower verbal memory scores for ACE D and APOE ε4 carriers, but AGT T carrier status was significantly associated with higher verbal memory scores (p=0.0188, p=0.0055, and p=0.0058, respectively). These results were only significant in the low-education group. In addition, medication-gene interactions were not significant predictors of BACS scores. ACE D and APOE ε4 carrier status, independent of medication use, was associated with lower verbal memory scores in patients with schizophrenia who had relatively lower CR, as identified by formal education. These results suggest that increasing CR may be protective against cognitive impairment that may be worsened by select cardiovascular risk alleles in patients with schizophrenia.
作者旨在研究认知功能障碍和心血管疾病风险的多个风险等位基因对认知功能的影响，并确定这些关系是否因认知储备（CR）或合并用药而在精神分裂症患者中有所不同。他们在门诊心理健康中心进行了一项横断面研究。共纳入 122 名符合精神分裂症谱系诊断标准的成年人，这些患者在研究入组前至少接受了 6 个月的稳定抗精神病药物治疗。根据受教育年限，患者被分为三组 CR：未完成高中学业或同等学历（低教育组[18 名患者]）、完成高中学业或同等学历（中等教育组[36 名患者]）或接受过高中以上教育（高教育组[68 名患者]）。对每位患者进行了以下药物基因组学变异的基因分型：AGT M268T（rs699）、ACE 插入/缺失（或 ACE I/D，rs1799752）和 APOE ε2、ε3 和 ε4（rs429358 和 rs7412）。CR 组之间的风险等位基因携带状态（按基因鉴定为 AGT M268 T 携带者、ACE D 携带者和 APOE ε4 携带者）没有显著差异。使用Brief Assessment of Cognition in Schizophrenia（BACS）量表评估认知功能。患者的平均年龄为 43.9±11.6 岁。CR 组之间的心血管危险因素，如高血压和高血脂的诊断，以及降压药和降脂药的使用，没有显著差异。混合模型显示，ACE D 和 APOE ε4 携带者的风险等位基因携带状态与言语记忆评分较低显著相关，而 AGT T 携带者的言语记忆评分较高（分别为 p=0.0188、p=0.0055 和 p=0.0058）。这些结果仅在低教育组中具有统计学意义。此外，药物-基因相互作用不是 BACS 评分的显著预测因素。ACE D 和 APOE ε4 携带状态，独立于药物使用，与认知储备相对较低的精神分裂症患者的言语记忆评分较低相关，这是通过正规教育来确定的。这些结果表明，增加 CR 可能对认知障碍有保护作用，而认知障碍可能会因精神分裂症患者中某些心血管风险等位基因而恶化。
