Age Matters: an Atypical Association Between Polymorphism of MTHFR and Clinical Phenotypes in Children with Schizophrenia.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism may increase the risk of schizophrenia in adults and aggravate related symptoms, while it is unknown whether similar risk applies in children with schizophrenia. While average onset age of schizophrenia is between the ages of 15 and 25, there are no studies on the relationship between MTHFR polymorphism and childhood-onset schizophrenia (COS). Here, we aimed to explore the risk of MTHFR polymorphism in children and examine the effects of MTHFR polymorphism on disease onset and clinical features in the COS patients. Pediatric patients with schizophrenia (n = 97) as well as age- and sex-matched controls (n = 92) were enrolled from the pediatric department. We evaluated clinical features including disease onset age, duration, Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), and Clinical Global Impression (CGI). The three major MTHFR genotypes (G1793A, C677T, and A1298C) were examined in all subjects and the association between MTHFR polymorphism and clinical features of schizophrenia was analyzed. The G1793A polymorphism and the total number of MTHFR risk alleles were associated with an increased risk of schizophrenia in children. The A1298C polymorphism contributed to prolong the duration time of schizophrenia. Inconsistent with expectations, no significant associations were found between MTHFR C677T polymorphism and schizophrenia in children. Both G1793A and multi-site MTHFR polymorphisms are associated with an increased risk of schizophrenia in children, while A1298C polymorphism contributes to prolonged disease duration. While C677T is known to play major roles in the risk of adult schizophrenia, our finding for the first time suggests an age-specific association between MTHFR polymorphisms and schizophrenia.