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MTHFR genotype and differential evolution of metabolic parameters after initiation of a second generation antipsychotic: an observational study

van Winkel, Ruuda b; Moons, Timc; Peerbooms, Odettea; Rutten, Barta; Peuskens, Josephb; Claes, Stephanc; van Os, Jima; De Hert, Marcb

International Clinical Psychopharmacology: September 2010 - Volume 25 - Issue 5 - pp 270-276
doi: 10.1097/YIC.0b013e32833bc60d
Original Articles

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;

e-mail: marc.de.hert@uc-kortenberg.be

Ruud van Winkel and Tim Moons contributed equally to the study

Received 30 December 2009 Accepted 5 May 2010

© 2010 Lippincott Williams & Wilkins, Inc.