Abstract
Although antipsychotic medication contributed to the improvement of psychotic symptoms and reduced relapse, it induced weight gain and metabolic syndrome during antipsychotic medication treatment, which was seriously concerning. To investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T (rs1801133) polymorphism with antipsychotic-induced weight gain and metabolism parameter change, we employed 1,868 patients with schizophrenia in this study and randomly allocated them to seven antipsychotic medication treatment groups. All patients received antipsychotics monotherapy and were followed up for 6 weeks. Height, body weight, and metabolic parameters of the patients were measured at baseline and at 2, 4, and 6 weeks after antipsychotic treatment. We genotyped blood DNA from patients for MTHFR C677T polymorphisms and performed quantitative analyses using analysis of variance (ANOVA) and the analysis of covariance (ANCOVA) among three genotype groups.We found a predominant association between MTHFR C677T and body weight mass index (BMI) change after 6-week risperidone treatment. After 6-week treatment of risperidone, the BMI change rate (%) of MTHFR C677 carriers was significantly higher than that of MTHFR TT genotype carriers [CC (2.81 ± 6.77)%, CT (3.79 ± 5.22)%, TT (1.42 ± 3.53)%, F = 4.749, P = 0.009]. Some of the abnormal metabolic parameters were found to be associated with the MTHFR 677T, including higher levels of low-density lipoprotein and waist circumference. Validation was performed in an independent cohort, consisting of 252 patients with schizophrenia treated with three atypical antipsychotic drugs. Overall, the MTHFR C677 was associated with high risk of antipsychotic-induced weight gain and metabolism abnormalities.
Highlights
Schizophrenia affects nearly 1% of the world population and is among the top 10 global causes of disability [1]
We examined the impact of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on weight changes and metabolic parameters in schizophrenia patients with antipsychotic treatment
We performed analysis of variance (ANOVA) to test the association of MTHFR gene C677T polymorphism with metabolic index at both baseline and after 6-week treatment (Table 2)
Summary
Schizophrenia affects nearly 1% of the world population and is among the top 10 global causes of disability [1]. Antipsychotic medication can induce weight gain and alteration of metabolic parameters, which influence treatment adherence and lead to diabetes, hyperglycemia, hypertension, and cardiac death [2,3,4,5]. MTHFR encoded methylenetetrahydrofolate reductase, which converts folate into the metabolically active form of 5-methyltetratydrofolate. It plays an important role in the metabolism of folate and homocysteine. It has been reported that the polymorphisms of MTHFR were associated with the metabolic syndrome in both the general population [10,11,12,13,14] and antipsychotic-administrated schizophrenia patients [15, 16], which makes the genetic variant of MTHFR a potential predictor for antipsychotic-induced metabolic side effects (e.g., weight gain) [15,16,17]. These research were not aligned together, and the influence of the variant of MTHFR-C677T on antipsychotic-induced weight gain remained unclear with rare related studies [18]
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