Low prevalence of lipid metabolism abnormalities in APOE ε2-genotype and male patients 60 years or older with schizophrenia

BACKGROUND Schizophrenia is a serious mental disorder largely manageable with atypical antipsychotics; however, these drugs have been associated with glucose/lipid metabolism issues such as diabetes and hyperlipidaemia. Apolipoprotein E (APOE) is the most abundant apolipoprotein, and APOE genotypes have been correlated with lipid metabolism phenotypes in an age-dependent manner. Studies examining the relationship between the APOE genotype and lipid abnormalities in patients with schizophrenia have been inconclusive, but primarily focused on adult patient populations. Therefore, we explored the correlations between the APOE genotype and glucose/lipid metabolism indicators and abnormalities in hospitalized patients 60 years or older with schizophrenia with a history of long-term antipsychotics use. METHODS We assessed APOE genotype, age, weight, height, blood glucose, triglycerides, cholesterol, high-density lipoprotein, and low-density lipoprotein in a total of 294 patients. APOE genotypes were divided into three groups: APOE ε2 (ε2/ε2 and ε2/ε3), APOE ε3 (ε3/ε3), and APOE ε4 (ε3/ε4 and ε4/ε4), and comparisons were conducted among these groups or according to ε2 carrier status. RESULTS APOE ε3/ε3 was the most common genotype (68.3%) and at least one ε3 allele was present in 81.8% of patients. There were no differences in antipsychotics type or dose according to the APOE genotype, but serum cholesterol values varied near significantly (P = 0.052) and low-density lipoprotein values varied significantly according to genotype (P < 0.05, lowest in the APOE ε2 genotype). Men had lower cholesterol and low-density lipoprotein levels (P < 0.05) than women. Compared to patients administered typical antipsychotics, those administered atypical antipsychotics had higher triglyceride, cholesterol, and low-density lipoprotein levels (P < 0.05). Stepwise linear regressions showed that cholesterol and low-density lipoprotein levels were influenced by sex, the APOE ε2 genotype, and atypical antipsychotics use. CONCLUSIONS In the context of atypical antipsychotics use, carriers of the APOE ε2-genotype and male patients with schizophrenia 60 years or older may be less likely to develop a lipid metabolism abnormality.