Cardiovascular Pharmacogenomics and Cognitive Function in Patients with Schizophrenia

Abstract

Study Objective

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.

Design

Cross-sectional study.

Setting

Ambulatory mental health centers.

Patients

A total of 122 adults with a schizophrenia spectrum diagnosis who were maintained on a stable antipsychotic regimen for at least 6 months prior to study enrollment; 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]).

Measurements and Main Results

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. Additionally, medication-gene interactions were not significant predictors of BACS scores.

Conclusion

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.

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