Low levels of serum serotonin and amino acids identified in migraine patients

Biochem Biophys Res Commun. 2018 Feb 5;496(2):267-273. doi: 10.1016/j.bbrc.2017.11.203. Epub 2017 Dec 30.

Abstract

Migraine is a highly disabling primary headache associated with a high socioeconomic burden and a generally high prevalence. The clinical management of migraine remains a challenge. This study was undertaken to identify potential serum biomarkers of migraine. Using Liquid Chromatography coupled to Mass Spectrometry (LC-MS), the metabolomic profile of migraine was compared with healthy individuals. Principal component analysis (PCA) and Orthogonal partial least squares-discriminant analysis (orthoPLS-DA) showed the metabolomic profile of migraine is distinguishable from controls. Volcano plot analysis identified 10 serum metabolites significantly decreased during migraine. One of these was serotonin, and the other 9 were amino acids. Pathway analysis and enrichment analysis showed tryptophan metabolism (serotonin metabolism), arginine and proline metabolism, and aminoacyl-tRNA biosynthesis are the three most prominently altered pathways in migraine. ROC curve analysis indicated Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine are potential sensitive and specific biomarkers for migraine. Our results show Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine may be as specific or more specific for migraine than serotonin which is the traditional biomarker of migraine. We propose that therapeutic manipulation of these metabolites or metabolic pathways may be helpful in the prevention and treatment of migraine.

Keywords: Amino acids; Metabolomics; Migraine; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine / analogs & derivatives*
  • Alanine / blood
  • Arginine / blood
  • Biomarkers / blood
  • Case-Control Studies
  • Chromatography, High Pressure Liquid / methods
  • Dipeptides / blood*
  • Discriminant Analysis
  • Female
  • Humans
  • Male
  • Metabolome
  • Methionine / blood*
  • Migraine Disorders / blood
  • Migraine Disorders / diagnosis*
  • Migraine Disorders / physiopathology
  • Principal Component Analysis
  • Proline / blood
  • RNA, Transfer, Amino Acyl / blood
  • ROC Curve
  • Serotonin / blood*
  • Tryptophan / blood

Substances

  • Biomarkers
  • Dipeptides
  • RNA, Transfer, Amino Acyl
  • Serotonin
  • N-methylalanine
  • glycylproline
  • Tryptophan
  • Arginine
  • Proline
  • Methionine
  • Alanine