Display options
Cite
Ellingrod VL, Grove TB, Burghardt KJ, et al. The effect of folate supplementation and genotype on cardiovascular and epigenetic measures in schizophrenia subjects. NPJ Schizophr. 2015;1:15046doi: 10.1038/npjschz.2015.46.
Ellingrod, V. L., Grove, T. B., Burghardt, K. J., Taylor, S. F., & Dalack, G. (2015). The effect of folate supplementation and genotype on cardiovascular and epigenetic measures in schizophrenia subjects. NPJ schizophrenia, 115046. https://doi.org/10.1038/npjschz.2015.46
Ellingrod, Vicki L, et al. "The effect of folate supplementation and genotype on cardiovascular and epigenetic measures in schizophrenia subjects." NPJ schizophrenia vol. 1 (2015): 15046. doi: https://doi.org/10.1038/npjschz.2015.46
Ellingrod VL, Grove TB, Burghardt KJ, Taylor SF, Dalack G. The effect of folate supplementation and genotype on cardiovascular and epigenetic measures in schizophrenia subjects. NPJ Schizophr. 2015 Nov 11;1:15046. doi: 10.1038/npjschz.2015.46. eCollection 2015. PMID: 27336047; PMCID: PMC4849464.
Copy Download .nbib Format: NLM
Share it on

NPJ Schizophr. 2015 Nov 11;1:15046. doi: 10.1038/npjschz.2015.46. eCollection 2015.

The effect of folate supplementation and genotype on cardiovascular and epigenetic measures in schizophrenia subjects.

NPJ schizophrenia

Vicki L Ellingrod, Tyler B Grove, Kyle J Burghardt, Stephan F Taylor, Gregory Dalack

Affiliations

  1. Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA; Department of Psychology, University of Michigan, Ann Arbor, MI, USA.
  2. Department of Psychology, University of Michigan , Ann Arbor, MI, USA.
  3. Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, MI, USA.
  4. Department of Psychiatry, University of Michigan , Ann Arbor, MI, USA.

PMID: 27336047 PMCID: PMC4849464 DOI: 10.1038/npjschz.2015.46

Abstract

BACKGROUND: Metabolic syndrome may be related to folate's pharmacogenetically regulated metabolism and atypical antipsychotic (AAP) exposure.

AIMS: We examined folate supplementation on metabolic measures, endothelial functioning (Reactive Hyperemia Index (RHI)), and global methylation in AAP-treated schizophrenia subjects meeting NCEP-ATP-III-a metabolic syndrome criteria.

METHODS: Subjects were given 5 mg/day open label folate for 3 months. Baseline and end point measurements included RHI, body mass index, fasting metabolic laboratory measures, C-reactive protein, homocysteine, IL-6, and leptin. Subjects were genotyped for methylenetetrahydrofolate reductase (MTHFR) 677C/T and catechol-O-methyltransferase (COMT) 158 Val/Met, as well as global DNA methylation using the LUminometric Methylation Assay (LUMA).

RESULTS: Thirty-five subjects (mean age 50±9 years and 70% Caucasian) were included. At end point, RHI improved by 20% (P=0.02), homocysteine decreased 14% (P=0.006), and IL-6 decreased 13% (P=0.09). At baseline, 61% met endothelial dysfunction criteria (RHI<1.67), which decreased to 27% (P=0.0006) at end point. The MTHFR 677C/C+COMT 158Met/Met group also showed significant reduction in those meeting endothelial dysfunction (83% baseline and 16% end point (P=0.001)). Global methylation levels increased after supplementation (4.3%, P<0.0001), with subjects receiving olanzapine or clozapine experiencing greater methylation changes after folate supplementation. Folate may reduce AAP-associated metabolic risks.

CONCLUSIONS: We report significant reductions in the number of subjects meeting endothelial dysfunction. Given that all subjects met metabolic syndrome criteria, this may prove as a useful avenue to reducing cardiovascular disease risk. MTHFR and COMT genotypes may affect response and underlying changes in DNA methylation may help to explain the mechanistic underpinnings of these findings.

References

  1. Cochrane Database Syst Rev. 2009 Oct 07;(4):CD006627 - PubMed
  2. Clin Cardiol. 2004 Mar;27(3):137-41 - PubMed
  3. Schizophr Res. 2011 Apr;127(1-3):41-5 - PubMed
  4. Schizophr Res. 2008 Jan;98(1-3):47-54 - PubMed
  5. J Biol Chem. 2000 Sep 22;275(38):29318-23 - PubMed
  6. J Psychopharmacol. 2011 Jun;25(6):715-21 - PubMed
  7. FASEB J. 2012 Jun;26(6):2712-8 - PubMed
  8. Prev Chronic Dis. 2006 Apr;3(2):A42 - PubMed
  9. Eur Heart J. 2010 May;31(9):1142-8 - PubMed
  10. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):168-75 - PubMed
  11. Epigenomics. 2012 Jun;4(3):261-8 - PubMed
  12. Pharmacogenomics J. 2013 Jun;13(3):264-71 - PubMed
  13. Eur J Cardiovasc Prev Rehabil. 2007 Oct;14(5):615-23 - PubMed
  14. Nutr Metab Cardiovasc Dis. 2010 Feb;20(2):140-6 - PubMed
  15. Expert Rev Cardiovasc Ther. 2005 May;3(3):465-71 - PubMed
  16. Prog Cardiovasc Dis. 2014 Jan-Feb;56(4):401-8 - PubMed
  17. Am J Hum Genet. 2004 Nov;75(5):807-21 - PubMed
  18. Schizophr Res. 2010 Nov;123(2-3):225-33 - PubMed
  19. Epigenetics. 2006 Jan-Mar;1(1):45-8 - PubMed
  20. J Am Coll Cardiol. 2004 Dec 7;44(11):2137-41 - PubMed
  21. Int J Obes (Lond). 2014 May;38(5):746-9 - PubMed
  22. Br J Psychiatry Suppl. 1989 Nov;(7):49-58 - PubMed
  23. Crit Pathw Cardiol. 2005 Dec;4(4):198-203 - PubMed
  24. Psychopharmacol Bull. 1988;24(1):101-4 - PubMed
  25. Arch Gen Psychiatry. 1961 Jun;4:561-71 - PubMed
  26. J Clin Psychopharmacol. 2012 Apr;32(2):261-5 - PubMed
  27. Clin Chem Lab Med. 2013 Mar 1;51(3):523-34 - PubMed
  28. Bioinformatics. 2005 Jan 15;21(2):263-5 - PubMed
  29. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R139-47 - PubMed
  30. Schizophr Res. 2011 Aug;130(1-3):20-6 - PubMed
  31. Isr Med Assoc J. 2000 Mar;2(3):246-7 - PubMed
  32. Am J Cardiol. 2002 Mar 7;89(5A):1C-2C - PubMed
  33. J Clin Psychopharmacol. 2010 Dec;30(6):706-10 - PubMed
  34. Reprod Health. 2014 Sep 26;11 Suppl 3:S3 - PubMed
  35. Circulation. 1997 Mar 4;95(5):1119-21 - PubMed
  36. Mayo Clin Proc. 2004 Dec;79(12):1514-20 - PubMed
  37. Curr Drug Metab. 2005 Feb;6(1):37-46 - PubMed
  38. Psychiatry Res. 2012 Jan 30;195(1-2):39-44 - PubMed
  39. J Clin Psychiatry. 2012 Feb;73(2):216-23 - PubMed
  40. Thromb Res. 1980 Apr 1-15;18(1-2):113-21 - PubMed
  41. BMC Med Genomics. 2013 Mar 05;6:7 - PubMed
  42. Schizophr Res. 2005 Dec 1;80(1):19-32 - PubMed
  43. Br J Clin Pharmacol. 2011 Mar;71(3):377-82 - PubMed
  44. Acta Psychiatr Scand Suppl. 1987;334:1-100 - PubMed

Publication Types

Grant support