Most second-generation antipsychotics (SGAs) induce metabolic disturbances, but large differences exist in the degree to which individual patients develop these. Little is known about genetic factors associated with differential liability. Cross-sectional studies suggested an association between polymorphisms in 5,10-methylenetetraydrofolate reductase (MTHFR) and metabolic syndrome in patients with schizophrenia. This study aimed to assess whether the C677T (rs1801133) or A1298C (rs1801131) polymorphism in the MTHFR gene predict differential evolution of metabolic parameters over the course of a 3-month follow-up period after initiation of an SGA. One hundred and four patients with schizophrenia initiated on a SGA were measured at baseline, 6 weeks and 3 months. MTHFR A1298C, but not C677T, genotype predicted pos-baseline increases in weight [β=2.5, standard error (SE)=0.92, P=0.006], waist circumference (β=2.0, SE=1.0, P=0.050), fasting glucose (β=2.8, SE=1.2, P=0.024) and glucose at 120 min during the Oral Glucose Tolerance Test (β=10.7, SE=4.5, P=0.018) following a de novo metabolic challenge with a specific SGA. A1298C allele carriers consistently displayed the most unfavorable evolution of metabolic parameters. Thus, MTHFR A1298C genotype may explain part of the individual liability to metabolic disturbances in patients with schizophrenia.
aDepartment of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, Maastricht, The Netherlands
bUniversity Psychiatric Centre, Catholic University, Leuven, Leuvensesteenweg, Kortenberg
cUniversity Psychiatric Centre, Catholic University Leuven, Herestraat, Leuven, Belgium
Correspondence to Marc De Hert, MD, PhD, University Psychiatric Centre Katholieke Universiteit Leuven, Campus Kortenberg., leuvensesteenweg 517, kortenberg 3070, Belgium
Tel: +32 27580511; fax: +32 02 759 53 80;
Ruud van Winkel and Tim Moons contributed equally to the study
Received 30 December 2009 Accepted 5 May 2010