Interictal, circulating sphingolipids in women with episodic migraine: A case-control study.
OBJECTIVE
To evaluate interictal, circulating sphingolipids in women migraineurs.


METHODS
In the fasting state, serum samples were obtained pain-free from 88 women with episodic migraine (EM; n=52) and from controls (n=36). Sphingolipids were detected and quantified by high-performance liquid chromatography coupled with tandem mass spectrometry using multiple reaction monitoring. Multivariate logistic regression was used to examine the association between serum sphingolipids and EM odds. A recursive partitioning decision tree based on the serum concentrations of 10 sphingolipids was used to determine the presence or absence of EM in a subset of participants.


RESULTS
Total ceramide (EM 6,502.9 ng/mL vs controls 10,518.5 ng/mL; p<0.0001) and dihydroceramide (EM 39.3 ng/mL vs controls 63.1 ng/mL; p<0.0001) levels were decreased in those with EM as compared with controls. Using multivariate logistic regression, each SD increase in total ceramide (odds ratio [OR] 0.07; 95% confidence interval [CI]: 0.02, 0.22; p<0.001) and total dihydroceramide (OR 0.05; 95% CI: 0.01, 0.21; p<0.001) levels was associated with more than 92% reduced odds of migraine. Although crude sphingomyelin levels were not different in EM compared with controls, after adjustments, every SD increase in the sphingomyelin species C18:0 (OR 4.28; 95% CI: 1.87, 9.81; p=0.001) and C18:1 (OR 2.93; 95% CI: 1.55, 5.54; p=0.001) was associated with an increased odds of migraine. Recursive portioning models correctly classified 14 of 14 randomly selected participants as EM or control.


CONCLUSIONS
These results suggest that sphingolipid metabolism is altered in women with EM and that serum sphingolipid panels may have potential to differentiate EM presence or absence.


METHODS
This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine.
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH. lpeterlin@jhmi.edu.
B Lee
BL
Peterlin
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Michelle M
MM
Mielke
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Alex M
AM
Dickens
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Subroto
S
Chatterjee
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Paul
P
Dash
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Guillermo
G
Alexander
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Rebeca V A
RV
Vieira
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Veera Venkata Ratnam
VV
Bandaru
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Joelle M
JM
Dorskind
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Gretchen E
GE
Tietjen
From the Department of Neurology (B.L.P., A.M.D., R.V.A.V., V.V.R.B., J.M.D., N.H.H.), Department of Pediatrics, Lipid Research Atherosclerosis Unit (S.C.), and Department of Psychiatry (N.H.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Sciences Research (M.M.M.), Division of Epidemiology, and Department of Neurology, Mayo Clinic, Rochester, MN; Department of Neurology (P.D.), Johns Hopkins Community Physicians, Baltimore, MD; Department of Neurology (G.A.), Drexel University College of Medicine, Philadelphia, PA; Department of Psychology (R.V.A.V.), Federal University of Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurology (G.E.T.), University of Toledo, OH.
Norman H
NH
Haughey
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood; D003863:Depression / Q000097:blood / Q000175:diagnosis; D005260:Female; D006801:Humans; D008875:Middle Aged; D008881:Migraine Disorders / Q000097:blood*; D016017:Odds Ratio; D013107:Sphingolipids / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
D002518:Ceramides; D013107:Sphingolipids; C109343:dihydroceramide