Interictal, circulating sphingolipids in women with episodic migraine

B. Lee Peterlin, Michelle M Mielke, Alex M. Dickens, Subroto Chatterjee, Paul Dash, Guillermo Alexander, Rebeca V A Vieira, Veera Venkata Ratnam Bandaru, Joelle M. Dorskind, Gretchen E. Tietjen, Norman H. Haughey

Research output: Contribution to journalArticle

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Abstract

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. Conclusion: 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. Classification of evidence: This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine.

Original languageEnglish (US)
Pages (from-to)1214-1223
Number of pages10
JournalNeurology
Volume85
Issue number14
DOIs
StatePublished - Oct 6 2015

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Sphingolipids
Migraine Disorders
Odds Ratio
Confidence Intervals
Serum
Sphingomyelins
Logistic Models
Social Adjustment
Decision Trees
Ceramides
Tandem Mass Spectrometry
Fasting
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Peterlin, B. L., Mielke, M. M., Dickens, A. M., Chatterjee, S., Dash, P., Alexander, G., ... Haughey, N. H. (2015). Interictal, circulating sphingolipids in women with episodic migraine. Neurology, 85(14), 1214-1223. https://doi.org/10.1212/WNL.0000000000002004

Interictal, circulating sphingolipids in women with episodic migraine. / Peterlin, B. Lee; Mielke, Michelle M; Dickens, Alex M.; Chatterjee, Subroto; Dash, Paul; Alexander, Guillermo; Vieira, Rebeca V A; Bandaru, Veera Venkata Ratnam; Dorskind, Joelle M.; Tietjen, Gretchen E.; Haughey, Norman H.

In: Neurology, Vol. 85, No. 14, 06.10.2015, p. 1214-1223.

Research output: Contribution to journalArticle

Peterlin, BL, Mielke, MM, Dickens, AM, Chatterjee, S, Dash, P, Alexander, G, Vieira, RVA, Bandaru, VVR, Dorskind, JM, Tietjen, GE & Haughey, NH 2015, 'Interictal, circulating sphingolipids in women with episodic migraine', Neurology, vol. 85, no. 14, pp. 1214-1223. https://doi.org/10.1212/WNL.0000000000002004
Peterlin BL, Mielke MM, Dickens AM, Chatterjee S, Dash P, Alexander G et al. Interictal, circulating sphingolipids in women with episodic migraine. Neurology. 2015 Oct 6;85(14):1214-1223. https://doi.org/10.1212/WNL.0000000000002004
Peterlin, B. Lee ; Mielke, Michelle M ; Dickens, Alex M. ; Chatterjee, Subroto ; Dash, Paul ; Alexander, Guillermo ; Vieira, Rebeca V A ; Bandaru, Veera Venkata Ratnam ; Dorskind, Joelle M. ; Tietjen, Gretchen E. ; Haughey, Norman H. / Interictal, circulating sphingolipids in women with episodic migraine. In: Neurology. 2015 ; Vol. 85, No. 14. pp. 1214-1223.
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abstract = "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. Conclusion: 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. Classification of evidence: This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine.",
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AU - Peterlin, B. Lee

AU - Mielke, Michelle M

AU - Dickens, Alex M.

AU - Chatterjee, Subroto

AU - Dash, Paul

AU - Alexander, Guillermo

AU - Vieira, Rebeca V A

AU - Bandaru, Veera Venkata Ratnam

AU - Dorskind, Joelle M.

AU - Tietjen, Gretchen E.

AU - Haughey, Norman H.

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N2 - 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. Conclusion: 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. Classification of evidence: This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine.

AB - 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. Conclusion: 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. Classification of evidence: This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine.

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