ADMC Publications

Wang T, Huynh K, Giles C, Mellett NA, Duong T, Nguyen A, Lim WLF, Smith AA, Olshansky G, Cadby G, Hung J, Hui J, Beilby J, Watts GF, Chatterjee P, Martins I, Laws SM, Bush AI, Rowe CC, Villemagne VL, Ames D, Masters CL, Taddei K, Doré V, Fripp J, Arnold M, Kastenmüller G, Nho K, Saykin AJ, Baillie R, Han X, Martins RN, Moses EK, Kaddurah-Daouk R, Meikle PJ. APOE ε2 resilience for Alzheimer’s disease is mediated by plasma lipid species: Analysis of three independent cohort studies. Alzheimers Dement. 2022 Jan 25; PMID: 35077012

Batra R, Arnold M, Wörheide MA, Allen M, Wang X, Blach C, Levey AI, Seyfried NT, Ertekin-Taner N, Bennett DA, Kastenmüller G, Kaddurah-Daouk RF, Krumsiek J, for the Alzheimer’s Disease Metabolomics Consortium (ADMC). The landscape of metabolic brain alterations in Alzheimer’s disease [Internet]. Neuroscience; 2021 Nov. Available from: http://biorxiv.org/lookup/doi/10.1101/2021.11.15.468698

Wörheide MA, Krumsiek J, Nataf S, Nho K, Greenwood AK, Wu T, Huynh K, Weinisch P, Römisch-Margl W, Lehner N, Consortium TAA, Initiative TADN, Consortium TADM, Baumbach J, Meikle PJ, Saykin AJ, Doraiswamy PM, Duijn C van, Suhre K, Kaddurah-Daouk R, Kastenmüller G, Arnold M. An Integrated Molecular Atlas of Alzheimer’s Disease [Internet]. medRxiv; 2021 [cited 2022 May 3]. p. 2021.09.14.21263565. Available from: https://www.medrxiv.org/content/10.1101/2021.09.14.21263565v1

Nho K, Kueider-Paisley A, Arnold M, MahmoudianDehkordi S, Risacher SL, Louie G, Blach C, Baillie R, Han X, Kastenmüller G, Doraiswamy PM, Kaddurah-Daouk R, Saykin AJ. Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression. Brain Commun. 2021;3(3):fcab139. PMCID: PMC8361396

Horgusluoglu E, Neff R, Song WM, Wang M, Wang Q, Arnold M, Krumsiek J, Galindo-Prieto B, Ming
C, Nho K, Kastenmüller G, Han X, Baillie R, Zeng Q, Andrews S, Cheng H, Hao K, Goate A, Bennett
DA, Saykin AJ, Kaddurah-Daouk R, Zhang B. Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer’s disease. Alzheimers Dement. United States; 2021 Nov 10; PMID: 34757660

Borkowski K, Taha AY, Pedersen TL, De Jager PL, Bennett DA, Arnold M, Kaddurah-Daouk R,
Newman JW. Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly
impaired subjects with fasting state stratification. Sci Rep. 2021 Sep 23;11(1):18964. PMCID:
PMC8460824

Borkowski K, Pedersen TL, Seyfried NT, Lah JJ, Levey AI, Hales CM, Dammer EB, Blach C, Louie G,
Kaddurah-Daouk R, Newman JW. Association of plasma and CSF cytochrome P450, soluble epoxide
hydrolase, and ethanolamide metabolism with Alzheimer’s disease. Alzheimers Res Ther. 2021 Sep
6;13(1):149. PMCID: PMC8422756

Varma VR, Wang Y, An Y, Varma S, Bilgel M, Doshi J, Legido-Quigley C, Delgado JC, Oommen AM,
Roberts JA, Wong DF, Davatzikos C, Resnick SM, Troncoso JC, Pletnikova O, O’Brien R, Hak E, Baak
BN, Pfeiffer R, Baloni P, Mohmoudiandehkordi S, Nho K, Kaddurah-Daouk R, Bennett DA, Gadalla
SM, Thambisetty M. Bile acid synthesis, modulation, and dementia: A metabolomic, transcriptomic, and
pharmacoepidemiologic study. PLoS Med. 2021 May;18(5):e1003615. PMCID: PMC8158920

Baloni P, Funk CC, Yan J, Yurkovich JT, Kueider-Paisley A, Nho K, Heinken A, Jia W, Mahmoudiandehkordi S, Louie G, Saykin AJ, Arnold M, Kastenmüller G, Griffiths WJ, Thiele I, Kaddurah-Daouk R, Price ND. Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease. Cell Rep Med. 2020 Nov 17;1(8):100138. PMCID: PMC7691449

Huynh K, Lim WLF, Giles C, Jayawardana KS, Salim A, Mellett NA, Smith AAT, Olshansky G, Drew BG, Chatterjee P, Martins I, Laws SM, Bush AI, Rowe CC, Villemagne VL, Ames D, Masters CL, Arnold M, Nho K, Saykin AJ, Baillie R, Han X, Kaddurah-Daouk R, Martins RN, Meikle PJ. Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease. Nat Commun 11, 5698 (2020). https://doi.org/10.1038/s41467-020-19473-7

Needham BD, Kaddurah-Daouk R, & Mazmanian SK. Gut microbial molecules in behavioural and neurodegenerative conditions. Nat Rev Neurosci 21, 717–731 (2020). https://doi.org/10.1038/s41583-020-00381-0

Wang J, Wei R, Xie G, Arnold M, Kueider-Paisley A, MahmoudianDehkordi S, Blach C, Baillie R, Han X, De Jager PL, Bennett DA, Kaddurah-Daouk R, JIa W. Peripheral serum metabolomic profiles inform central cognitive impairment. Sci Rep 10, 14059 (2020). https://doi.org/10.1038/s41598-020-70703-w

Kling MA, Goodenowe DB, Senanayake V, MahmoudianDehkordi S, Arnold M, Massaro TJ, Baillie R, Han X, Leung YY, Saykin AJ, Nho K, Kueider-Paisley A, Tenenbaum JD, Wang LS, Shaw LM, Trojanowski JQ, Kaddurah-Daouk RF; Alzheimer’s Disease Metabolomics Consortium (ADMC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Circulating ethanolamine plasmalogen indices in Alzheimer’s disease: Relation to diagnosis, cognition, and CSF tau. Alzheimers Dement. 2020 Sep;16(9):1234-1247. doi: 10.1002/alz.12110. Epub 2020 Jul 27. PMID: 32715599.

Bernath MM, Bhattacharyya S, Nho K, Barupal DK, Fiehn O, Baillie R, Risacher SL, Arnold M, Jacobson T, Trojanowski JQ, Shaw LM, Weiner M, Doraiswamy PM, Kaddurah-Daouk R, Saykin AJ, for the Alzheimer’s Disease Neuroimaging Initiative and Alzheimer’s Disease Metabolomics Consortium Neurology May 2020, 94 (20) e2088-e2098; doi: 10.1212/WNL.0000000000009436

Zhao N, Ren Y, Yamazaki Y, Qiao W, Li F, Felton LM, Mahmoudiandehkordi S, Kueider-Paisley A, Sonoustoun B, Arnold M, Shue F, Zheng J, Attrebi ON, Martens YA, Li Z, Bastea L, Meneses AD, Chen K, Thompson JW, St John-Williams L, Tachibana M, Aikawa T, Oue H, Job L, Yamazaki A, Liu CC, Storz P, Asmann YW, Ertekin-Taner N, Kanekiyo T, Kaddurah-Daouk R, Bu G. Alzheimer’s Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways. Neuron. 2020 Jun 3;106(5):727-742.e6. doi: 10.1016/j.neuron.2020.02.034. Epub 2020 Mar 20. PMID: 32199103; PMCID: PMC7388065.

Arnold M, Nho K, Kueider-Paisley A, Massaro T, Huynh K, Brauner B, MahmoudianDehkordi S, Louie G, Moseley MA, Thompson JW, John-Williams LS, Tenenbaum JD, Blach C, Chang R, Brinton RD, Baillie R, Han X, Trojanowski JQ, Shaw LM, Martins R, Weiner MW, Trushina E, Toledo JB, Meikle PJ, Bennett DA, Krumsiek J, Doraiswamy PM, Saykin AJ, Kaddurah-Daouk R, Kastenmüller G. Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome. Nat Commun. 2020 Mar 2;11(1):1148. PMCID: PMC7052223

Barupal DK, Baillie R, Fan S, Saykin AJ, Meikle PJ, Arnold M, Nho K, Fiehn O, Kaddurah-Daouk R. Sets of coregulated serum lipids are associated with Alzheimer’s disease pathophysiology. Alzheimers Dement (Amst). 2019 Dec;11:619–627. PMCID: PMC6732667

St John-Williams L, Mahmoudiandehkordi S, Arnold M, Massaro T, Blach C, Kastenmüller G, Louie G, Kueider-Paisley A, Han X, Baillie R, Motsinger-Reif AA, Rotroff D, Nho K, Saykin AJ, Risacher SL, Koal T, Moseley MA, Tenenbaum JD, Thompson JW, Kaddurah-Daouk R. Bile acids targeted metabolomics and medication classification data in the ADNI1 and ADNIGO/2 cohorts. Sci Data. 2019 Oct 17;6(1):212. PMCID: PMC6797798

Nho K, Kueider-Paisley A, Ahmad S, MahmoudianDehkordi S, Arnold M, Risacher SL, Louie G, Blach C, Baillie R, Han X, Kastenmüller G, Trojanowski JQ, Shaw LM, Weiner MW, Doraiswamy PM, van Duijn C, Saykin AJ, Kaddurah-Daouk R. Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers. JAMA Netw Open. 2019 Jul 3;2(7):e197978. PMCID: PMC6669786

Nho K, Kueider-Paisley A, MahmoudianDehkordi S, Arnold M, Risacher SL, Louie G, Blach C, Baillie R, Han X, Kastenmüller G, Jia W, Xie G, Ahmad S, Hankemeier T, van Duijn CM, Trojanowski JQ, Shaw LM, Weiner MW, Doraiswamy PM, Saykin AJ, Kaddurah-Daouk R. Altered bile acid profile in mild cognitive impairment and Alzheimer’s disease: Relationship to neuroimaging and CSF biomarkers. Alzheimers Dement. 2019 Feb;15(2):232–244. PMCID: PMC6454538

MahmoudianDehkordi S, Arnold M, Nho K, Ahmad S, Jia W, Xie G, Louie G, Kueider-Paisley A, Moseley MA, Thompson JW, St John Williams L, Tenenbaum JD, Blach C, Baillie R, Han X, Bhattacharyya S, Toledo JB, Schafferer S, Klein S, Koal T, Risacher SL, Kling MA, Motsinger-Reif A, Rotroff DM, Jack J, Hankemeier T, Bennett DA, De Jager PL, Trojanowski JQ, Shaw LM, Weiner MW, Doraiswamy PM, van Duijn CM, Saykin AJ, Kastenmüller G, Kaddurah-Daouk R. Altered bile acid profile associates with cognitive impairment in Alzheimer’s disease-An emerging role for gut microbiome. Alzheimers Dement. 2019 Jan;15(1):76–92. PMCID: PMC6487485

Jia W, Rajani C, Kaddurah-Daouk R, Li H. Expert insights: The potential role of the gut microbiome-bile acid-brain axis in the development and progression of Alzheimer’s disease and hepatic encephalopathy. Med Res Rev; 2019; Dec 5. doi: 10.1002/med.21653.

Wang J, Wei R, Xie G, Arnold M, Louie G, MahmoudianDehkordi S, Blach C, Baillie R, Han X, De Jager P, Bennett D, Kaddurah-Daouk R, Jia W, for the Alzheimer’s Disease Metabolomics Consortium. Peripheral Serum Metabolomic Profiles Inform Antecedent Central Cognitive Impairment in Older Adults. 2019; bioRxiv 837989; https://doi.org/10.1101/837989

Baloni P, Funk CC, Yan J, Yurkovich JT, Kueider-Paisley A, Nho K, Heinken A, Jia W, Mahmoudiandehkordi S, Louie G, Saykin AJ, Arnold M, Kastenmuller G, Griffiths WJ, Thiele I, Kaddurah-Daouk R, Price ND. Identifying Differences in Bile Acid Pathways for Cholesterol Clearance in Alzheimer’s Disease Using Metabolic Networks of Human Brain Regions. 2019; bioRxiv 782987; doi: https://doi.org/10.1101/782987

Barupal D, Fan S, Wancewicz B, Cajka T, Sa M, Showalter MR, Baillie R, Tenenbaum JD, Louie G, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Metabolomics Consortium; Kaddurah-Daouk R, & Fiehn O. Generation and quality control of lipidomics data for the Alzheimer’s Disease Neuroimaging Cohort. Nat Sci Data. 2018; 5. PMID: 30457571 doi: 10.1038/sdata.2018.26

Bernath M, Bhattacharyya S, Nho K, Barupal D, Fiehn O, Baillie R, Risacher S, Arnold M, Jacobson T. Trojanowsli J, Shaw L, Weiner M, Kaddurah-Daouk R, Saykin A. Serum triglycerides in Alzhiemer’s disease: Relation to neuroimaging and CSF biomarkers. 2018. bioRxiv 441394; doi: https://doi.org/10.1101/441394

Varma VR, Oommen AM, Varma S, Casanova R, An Y, Andrews RM, O’Brien R, Pletnikova O, Troncoso JC, Toledo J, Baillie R, Arnold M, Kastenmueller G, Nho K, Doraiswamy PM, Saykin AJ, Kaddurah-Daouk R, Legido-Quigley C, Thambisetty M. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study. PLoS Med. 2018;15(1)(3). https://doi.org/10.1371/journal.pmed.1002482

Kaddurah-Daouk R. Genomics and imaging data informed metabolomics: A biochemical roadmap for Alzheimer disease. Alzheimers Dement. 2017: 13(7); 542. doi: https://doi.org/10.1016/j.jalz.2017.07.129

Toledo JB, Arnold M, Kastenmuller G, Chang R, Baillie RA, Han XL, Thambisetty M, Tenenbaum JD, Suhre K, Thompson JW, St John-Williams L, MahmoudianDehkordi S, Rotroff DM, Jack JR, Motsinger-Reif A, Risacher SL, Blach C, Lucas JE, Massaro T, Louie G, Zhu HJ, Dallmann G, Klavins K, Koal T, Kim S, Nho K, Shen L, Casanova R, Varma S, Legido-Quigley C, Moseley MA, Zhu KX, Henrion MYR, van der Lee SJ, Harms AC, Demirkan A, Hankemeier T, van Duijn CM, Trojanowski JQ, Shaw LM, Saykin AJ, Weiner MW, Doraiswamy PM, Kaddurah-Daouk R, Neuroimaging AsD, Metabolomics AD. Metabolic network failures in Alzheimer’s disease: A biochemical road map. Alzheimers Dement. 2017;13(9):965-84.(2) PMID: 28341160 PMCID: PMC5866045 DOI: 10.1016/j.jalz.2017.01.020

St John-Williams L, Blach C, Toledo JB, Rotroff DM, Kim S, Klavins K, Baillie R, Han XL, Mahmoudiandehkordi S, Jack J, Massaro TJ, Lucas JE, Louie G, Motsinger-Reif AA, Risacher SL, Saykin AJ, Kastenmuller G, Arnold M, Koal T, Moseley MA, Mangravite LM, Peters MA, Tenenbaum JD, Thompson JW, Kaddurah-Daouk R. Data Descriptor: Targeted metabolomics and medication classification data from participants in the ADNI1 cohort. Nat Sci Data. 2017;4. PMID: 29039849(4) doi: 10.1038/sdata.2017.140

Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmüller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R. Metabolomics enables precision medicine: “A White Paper, Community Perspective”.for “Precision Medicine and Pharmacometabolomics Task Group”-Metabolomics Society Initiative. Metabolomics. 2016;12(10):149. Epub 2016 Sep 2. PMID:27642271(5) doi: 10.1007/s11306-016-1094-6

Kim S, Nho K, Ramanan VK, Lai D, Foroud TM, Lane K, Murrell JR, Gao S, Hall KS, Unverzagt FW, Baiyewu O, Ogunniyi A, Gureje O, Kling MA, Doraiswamy PM, Kaddurah-Daouk R, Hendrie HC, Saykin AJ. Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians. Journal of Alzheimer’s disease : JAD. 2016;49(4):991-1003. Epub 2015/11/01. doi: 10.3233/jad-150651. PMCID: PMC4822513 DOI: 10.3233/JAD-150651

Saykin AJ, Shen L, Yao X, Kim S, Nho K, Risacher SL, Ramanan VK, Foroud TM, Faber KM, Sarwar N, Munsie LM, Hu X, Soares HD, Potkin SG, Thompson PM, Kauwe JS, Kaddurah-Daouk R, Green RC, Toga AW, Weiner MW. Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans. Alzheimers Dement. 2015;11(7):792-814. Epub 2015/07/22. doi: 10.1016/j.jalz.2015.05.009. PubMed PMID: 26194313; PMCID: PMC4510473.

Kaddurah-Daouk R, Zhu H, Sharma S, Bogdanov M, Rozen SG, Matson W, Oki NO, Motsinger-Reif AA, Churchill E, Lei Z, Appleby D, Kling MA, Trojanowski JQ, Doraiswamy PM, Arnold SE; Pharmacometabolomics Research Network. Alterations in metabolic pathways and networks in Alzheimer’s disease. Transl Psychiatry 2013 Apr 9;3:e244. doi: 10.1038/tp.2013.18. PubMed PMID: 23571809; PubMed Central PMCID: PMC3641405.

Motsinger-Reif AA, Zhu H, Kling MA, Matson W, Sharma S, Fiehn O, Reif DM, Appleby DH, Doraiswamy PM, Trojanowski JQ, Kaddurah-Daouk R, Arnold SE. Comparing metabolomic and pathologic biomarkers alone and in combination for discriminating Alzheimer’s disease from normal cognitive aging. Acta Neuropathol Commun 2013 Jun 27;1(1):28. doi: 10.1186/2051-5960-1-28. PubMed PMID: 24252434; PubMed Central PMCID: PMC3893491.

Han X, Rozen S, Boyle SH, Hellegers C, Cheng H, Burke JR, Welsh-Bohmer KA, Doraiswamy PM, Kaddurah-Daouk R. Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One 2011;6(7):e21643. doi: 10.1371/journal.pone.0021643. Epub 2011 Jul 11. PubMed PMID: 21779331; PubMed Central PMCID: PMC3136924.

Kaddurah-Daouk R, Rozen S, Matson W, Han X, Hulette CM, Burke JR, Doraiswamy PM, Welsh-Bohmer KA. Metabolomic changes in autopsy-confirmed Alzheimer’s disease. Alzheimers Dement 2011 May;7(3):309-17. doi: 10.1016/j.jalz.2010.06.001. Epub 2010 Nov 13. PubMed PMID: 21075060; PubMed Central PMCID: PMC3061205.

Publications related to metabolomics in precision medicine

Reviews

Kaddurah-Daouk R, Weinshilboum R; Pharmacometabolomics Research Network. Metabolomic Signatures for Drug Response Phenotypes: Pharmacometabolomics Enables Precision Medicine.Clin Pharmacol Ther. 2015 Jul;98(1):71-5. doi: 10.1002/cpt.134. Epub 2015 Jun 4. PMID: 25871646

Kling MA, Trojanowski JQ, Wolk DA, Lee VM, Arnold SE. Vascular disease and dementias: paradigm shifts to drive research in new directions. Alzheimers Dement 2013 Jan;9(1):76-92. doi: 10.1016/j.jalz.2012.02.007. Epub 2012 Nov 22. PubMed PMID: 23183137; PubMed Central PMCID: PMC3640817.

Kaddurah-Daouk R, Weinshilboum RM. Pharmacometabolomics: Implications for Clinical Pharmacology and Systems Pharmacology. Clin Pharmacol Ther. 2013 Nov 5. doi: 10.1038/clpt.2013.217.

Kaddurah-Daouk R, Krishnan KR. Metabolomics: a global biochemical approach to the study of central nervous system diseases. Neuropsychopharmacology 2009 Jan;34(1):173-86. doi: 10.1038/npp.2008.174. PubMed PMID: 18843269.

Quinones MP, Kaddurah-Daouk R. Metabolomics tools for identifying biomarkers for neuropsychiatric diseases. Neurobiol Dis 2009 Aug;35(2):165-76. doi: 10.1016/j.nbd.2009.02.019. Epub 2009 Mar 19. PubMed PMID: 19303440.

Kaddurah-Daouk R, Kristal BS, Weinshilboum RM.(2008). Metabolomics: A global biochemical approach to drug response and disease. Annu Rev Pharmacol Toxicol 48: 653-683.

Variation of response to treatment

Bhattacharyya S, Ahmed AT, Arnold M, Liu D, Luo C, Zhu H, Mahmoudiandehkordi S, Neavin D, Louie G, Dunlop BW, Frye MA, Wang L, Weinshilboum RM, Krishnan RR, Rush AJ, Kaddurah-Daouk R. Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients. Transl Psychiatry; 2019; 9(1): 173; doi:10.1038/s41398-019-0507-5

Shahin MH, Gong Y, McDonough CW, Rotroff DM, Beitelshees AL, Garrett TJ, Gums JG, Motsinger-Reif A, Chapman AB, Turner ST, Boerwinkle E, Frye RF, Fiehn O, Cooper-DeHoff RM, Kaddurah-Daouk R, Johnson JA. A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration. Hypertension (Dallas, Tex : 1979). 2016;68(3):621-9. Epub 2016/07/07. doi: 10.1161/hypertensionaha.116.07328. PubMed PMID: 27381900; PMCID: PMC4982802.

Rotroff DM, Oki NO, Liang X, Yee SW, Stocker SL, Corum DG, Meisner M, Fiehn O, Motsinger-Reif AA, Giacomini KM, Kaddurah-Daouk R. Pharmacometabolomic Assessment of Metformin in Non-diabetic, African Americans. Frontiers in pharmacology. 2016;7:135. Epub 2016/07/06. doi: 10.3389/fphar.2016.00135. PubMed PMID: 27378919; PMCID: PMC4906013.

Rotroff DM, Corum DG, Motsinger-Reif A, Fiehn O, Bottrel N, Drevets WC, Singh J, Salvadore G, Kaddurah-Daouk R. Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants. Translational psychiatry. 2016;6(9):e894. Epub 2016/09/21. doi: 10.1038/tp.2016.145. PubMed PMID: 27648916; PMCID: PMC5048196.

Neavin D, Kaddurah-Daouk R, Weinshilboum R. Pharmacometabolomics informs Pharmacogenomics. Metabolomics. 2016;12(7). Epub 2016/08/16. doi: 10.1007/s11306-016-1066-x. PubMed PMID: 27516730; PMCID: PMC4976774.

Gupta M, Neavin D, Liu D, Biernacka J, Hall-Flavin D, Bobo WV, Frye MA, Skime M, Jenkins GD, Batzler A, Kalari K, Matson W, Bhasin SS, Zhu H, Mushiroda T, Nakamura Y, Kubo M, Wang L, Kaddurah-Daouk R, Weinshilboum RM. TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics. Molecular psychiatry. 2016; 21(12):1717-25. Epub 2016/02/24. doi: 10.1038/mp.2016.6. PubMed PMID: 26903268; PMCID: PMC5003027.

de Oliveira FA, Shahin MH, Gong Y, McDonough CW, Beitelshees AL, Gums JG, Chapman AB, Boerwinkle E, Turner ST, Frye RF, Fiehn O, Kaddurah-Daouk R, Johnson JA, Cooper-DeHoff RM. Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach. Metabolomics. 2016;12(8):129. doi: 10.1007/s11306-016-1076-8.

Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmuller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R. Metabolomics enables precision medicine: “A White Paper, Community Perspective”. Metabolomics. 2016; 12(10):149. Epub 2016/09/20. doi: 10.1007/s11306-016-1094-6. PubMed PMID: 27642271; PMCID: PMC5009152.

Wang Z, Maity A, Hsiao CK, Voora D, Kaddurah-Daouk R, Tzeng JY. Module-based association analysis for omics data with network structure. PLoS One. 2015;10(3):e0122309. Epub 2015/03/31. doi: 10.1371/journal.pone.0122309. PubMed PMID: 25822417; PMCID: PMC4378989.

Sumner LW, Styczynski M, McLean J, Fiehn O, Jander G, Liao J, Sumner S, Britz-McKibbin P, Welti R, Jones AD, Dorrestein PC, Bearden D, Kaddurah-Daouk R. Introducing the USA Plant, Algae and Microbial Metabolomics Research Coordination Network (PAMM-NET). Metabolomics. 2015;11(1):3-5. Epub 2015/02/01. doi: 10.1007/s11306-014-0755-6. PubMed PMID: 28018159; PMCID: PMC5178969.

Rotroff DM, Shahin MH, Gurley SB, Zhu H, Motsinger-Reif A, Meisner M, Beitelshees AL, Fiehn O, Johnson JA, Elbadawi-Sidhu M, Frye RF, Gong Y, Weng L, Cooper-DeHoff RM, Kaddurah-Daouk R. Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes. CPT: pharmacometrics & systems pharmacology. 2015;4(11):669-79. doi: 10.1002/psp4.12017. PubMed PMID: 26783503; PMCID: PMC4716583

Rasmussen HB, Bjerre D, Linnet K, Jurgens G, Dalhoff K, Stefansson H, Hankemeier T, Kaddurah-Daouk R, Taboureau O, Brunak S, Houmann T, Jeppesen P, Pagsberg AK, Plessen K, Dyrborg J, Hansen PR, Hansen PE, Hughes T, Werge T. Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics. Pharmacogenomics. 2015;16(6):649-65. Epub 2015/04/22. doi: 10.2217/pgs.15.7. PubMed PMID: 25896426.

Emwas AH, Luchinat C, Turano P, Tenori L, Roy R, Salek RM, Ryan D, Merzaban JS, Kaddurah-Daouk R, Zeri AC, Nagana Gowda GA, Raftery D, Wang Y, Brennan L, Wishart DS. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review. Metabolomics. 2015;11(4):872-94. Epub 2015/06/26. doi: 10.1007/s11306-014-0746-7. PubMed PMID: 26109927; PMCID: PMC4475544.

Ellero-Simatos S, Beitelshees AL, Lewis JP, Yerges-Armstrong LM, Georgiades A, Dane A, Harms AC, Strassburg K, Guled F, Hendriks MM, Horenstein RB, Shuldiner AR, Hankemeier T, Kaddurah-Daouk R. Oxylipid Profile of Low-Dose Aspirin Exposure: A Pharmacometabolomics Study. Journal of the American Heart Association. 2015;4(10):e002203. Epub 2015/10/28. doi: 10.1161/jaha.115.002203. PubMed PMID: 26504148; PMCID: PMC4845113.

Boyle SH, Georgiades A, Brummett BH, Barefoot JC, Siegler IC, Matson WR, Kuhn CM, Grichnik K, Stafford-Smith M, Williams RB, Kaddurah-Daouk R, Surwit RS. Associations between central nervous system serotonin, fasting glucose, and hostility in African American females. Annals of behavioral medicine . 2015;49(1):49-57. Epub 2014/05/09. doi: 10.1007/s12160-014-9626-7. PubMed PMID: 24806470; PMCID: PMC4500110.

Bouhifd M, Beger R, Flynn T, Guo L, Harris G, Hogberg H, Kaddurah-Daouk R, Kamp H, Kleensang A, Maertens A, Odwin-DaCosta S, Pamies D, Robertson D, Smirnova L, Sun J, Zhao L, Hartung T. Quality assurance of metabolomics. Altex. 2015;32(4):319-26. Epub 2015/11/05. doi: 10.14573/altex.1509161. PubMed PMID: 26536290.

Studies from Pharmacometabolomics Research Network- Applications of Metabolomics in Precision Medicine

Mood disorders

Ahmed AT, MahmoudianDehkordi S, Bhattacharyya S, Arnold M, Liu D, Neavin D, Moseley MA, Thompson JW, Williams LSJ, Louie G, Skime MK, Wang L, Riva-Posse P, McDonald WM, Bobo WV, Craighead WE, Krishnan R, Weinshilboum RM, Dunlop BW, Millington DS, Rush AJ, Frye MA, Kaddurah-Daouk R; Mood Disorders Precision Medicine Consortium (MDPMC). Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes. J Affect Disord; 2020; 264:90-97. doi: 10.1016/j.jad.2019.11.122

Bhattacharyya S, Dunlop BW, Mahmoudiandehkordi S, Ahmed AT, Louie G, Frye MA, Weinshilboum RM, Krishnan RR, Rush AJ, Mayberg HS, Craighead WE, and Kaddurah-Daouk R. Pilot Study of Metabolomic Clusters as State Markers of Major Depression and Outcomes to CBT Treatment. Front NeuroSci; 2019; 13; 926. doi: http://10.3389/fnins.2019.00926

Liu D, Ray B, Neavin DR, Zhang J, Athreya AP, Biernacka JM, Bobo WV, Hall-Flavin DK, Skime MK, Zhu H, Jenkins GD, Batzler A, Kalari KR, Boakye-Agyeman F, Matson WR, Bhasin SS, Mushiroda T, Nakamura Y, Kubo M, Iyer RK, Wang L, Frye MA, Kaddurah-Daouk R, Weinshilboum RM. Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics. Trans Psychiatry; 2018; 8(1); doi: 10.1038/s41398-017-0056-8

Ahmed AT, Frye MA, Rush AJ, Biernacka JM, Craighead WE, McDonald WM, Bobo WV, Riva-Posse P, Tye SJ, Mayberg HS, Flavin DH, Skime MK, Jenkins GD, Wang L, Krishnan RR, Weinshilboum RM, Kaddurah-Daouk R, Dunlop BW, and The Mood Disorders Precision Medicine Consortium (MDPMC). Mapping Depression Rating Scale Phenotypes onto Research Domain Criteria (RDoC) to Inform Biological Research in Mood Disorders. J Affect Disord; 2018; 238:1-7. doi: 10.1016/j.jad.2018.05.005

Athreya A, Iyer R, Neavin D, Wang L, Weinshilboum R, Kaddurah-Daouk R, Rush J, Frye M, Bobo W.
Augmentation of Physician Assessments with Multi-Omics Enhances Predictability of Drug Response: A Case Study of Major Depressive Disorder. IEEE Comput Intell Mag; 2018; 13(3): 20-31. doi: 10.1109/MCI.2018.2840660

Fan TWM, Yuan P, Lane AN, Higashi RM, Wang Y, Hamidi AB, Zhou R, Guitart Z, Chen G, Manji HK, Kaddurah-Daouk R. Stable isotope-resolved metabolomic analysis of lithium effects on glial-neuronal metabolism and interactions. Metabolomics; 2010; 6: 165-179.

Kaddurah-Daouk R, Yuan P, Boyle SH, Matson W, Wang Z, Zeng Z, Zhu H, Dougherty GG, Yao JK, Chen G, Guitart X, Carlson PJ, Neumeister A, Zarate C, Krishnan RR, Manji HK, Drevets W. Cerebrospinal Fluid Metabolome in Mood Disorders. Science Reports; 2012; 2:667. doi: 10.1038.

Kaddurah-Daouk R, Boyle SH, Matson W, Sharma S, Matson S, Zhu H, Bogdanov MB, Churchill E, Krishnan RR, Rush AJ, Pickering E, Delnomdedieu M. Pretreatment Metabotype as a Predictor of Response to Sertraline or Placebo in Depressed Outpatients: A Proof of Concept. Translational Psychiatry; 2011; Jul, 1 (7): e26; doi:10.1038/tp.2011.22.

Kaddurah-Daouk R, Bogdanov MB, Wikoff WR, Zhu H, Boyle SH, Churchill E, Wang Z, Rush AJ, Krishnan RR, Pickering E, Delnomdedieu M, Fiehn O. Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo. Transl Psychiatry; 2013; 3:e223. doi: 10.1038/tp.2012.142.

Zhu H, Bogdanov MB, Boyle SH, Matson W, Sharma S, Matson S, Churchill E, Fiehn O, Rush JA, Krishnan RR, Pickering E, Delnomdedieu M, Kaddurah-Daouk R, Network PR. (2013). Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder – possible role for methoxyindole pathway. PLoS One. 2013 Jul 17, 8(7):e68283. doi: 10.1371.

Ji Y, Hebbring S, Zhu H, Jenkins GD, Biernacka J, Snyder K, Drews M, Fiehn O, Zeng Z, Schaid D, Mrazek DA, Kaddurah-Daouk R, Weinshilboum RM. Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics. Clin Pharmacol Ther. ; 2011; 89(1):97-104.

Abo R, Hebbring S, Ji Y, Zhu H, Zeng ZB, Batzler A, Jenkins GD, Biernacka J, Snyder K, Drews M, Fiehn O, Fridley B, Schaid D, Kamatani N, Nakamura Y, Kubo M, Mushiroda T, Kaddurah-Daouk R, Mrazek DA, Weinshilboum RM. Merging pharmacometabolomics with pharmacogenomics using ‘1000 Genomes’ single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics. Pharmacogenet Genomics. 2012; Apr;22(4):247-53.

Statins

Kaddurah-Daouk R, Baillie RA, Zhu H, Zeng ZB, Wiest MM, Nguyen UT, Watkins SM, Krauss RM. Lipidomic analysis of variation in response to simvastatin in the cholesterol and pharmacogenetics study. Metabolomics; 2010; 6:191–201.

Kaddurah-Daouk R, Baillie RA, Zhu H, Zeng ZB, Wiest MM, Nguyen UT, Wojnoonski K, Watkins SM, Trupp M, Krauss RM. Enteric Microbiome correlates with response to simvastatin treatment. PLoS One; 2011; 6(10):e25482.

Trupp M, Zhu H, Wikoff WR, Baillie RA, Zeng ZB, Karp PD, Fiehn O, Krauss RM, Kaddurah-Daouk R. Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment. PLoS One; 2012; ;7(7):e38386. doi: 10.1371/journal.pone.0038386. Epub 2012 Jul 9.

Krauss R, Zhu H, Kaddurah-Daouk R. Pharmacometabolomics of statin Response. Clin Pharmacol Ther.; 2013; Aug 14. doi: 10.1038

Elbadawi-Sidhu M, Baillie RA, Zhu H, Chen Y-D I, Goodarzi MO, Rotter JI, Krauss RM, Fiehn O & Kaddurah-Daouk R. Pharmacometabolomic signature links simvastatin therapy and insulin resistance. Metabolomics; 2017; 13:11, https://link.springer.com/article/10.1007/s11306-016-1141-3

Anti-platelet

Yerges-Armstrong LM, Ellero-Simatos S, Georgiades A, Zhu H, Lewis JP, Horenstein RB, Beitelshees AL, Dane A, Reijmers T, Hankemeier T, Fiehn O, Shuldiner AR, Kaddurah-Daouk R. (2013). Purine Pathway Implicated in Mechanism of Resistance to Aspirin Therapy: Pharmacometabolomics-Informed Pharmacogenomics. Clin Pharmacol Ther. 2013 Jun 11. doi: 10.1038.

Lewis JP, Yerges-Armstrong LM, Ellero-Simatos S, Georgiades A, Kaddurah-Daouk R, Hankemeier T. Integration of Pharmacometabolomic and Pharmacogenomic Approaches Reveals Novel Insights into Antiplatelet Therapy. Clin Pharmacol Ther.; 2013; Jul 26. doi: 10.1038/clpt.2013.153

Anti-hypertensives

Wikoff WR, Frye RF, Zhu H, Boyle S, Churchill E, Gong Y, Cooper-Deho RM, Beitelshees AL, Lane A, Chapman AB, Turner ST, Fiehn O, Johnson JA, Kaddurah-Daouk R. (2013). Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment. March. PLoS One 3(8). e57639.

Shahin MH, Gong Y, Frye RF, Rotroff DM, Beitelshees AL, Baillie RA, Chapman AB, Gums JG, Turner ST, Boerwinkle E, Motsinger-Reif A, Fiehn O, Cooper-DeHoff RM, Han X, Kaddurah-Daouk R, Johnson JA. Sphingolipid Metabolic Pathway Impacts Thiazide Diuretics Blood Pressure Response: Insights From Genomics, Metabolomics, and Lipidomics. J Am Heart Assoc; 2017; 29; 7(1); doi: 10.1161/JAHA.117.006656

Metabolomic Studies in CNS Diseases: Our Network Experience

Yao JK, Dougherty GG, Reddy RD, Matson WR, Kaddurah-Daouk R, Keshavan MS. Associations between purine metabolites and monoamine neurotransmitters in first-episode psychosis. Front Cell Neurosci. 2013 Jun 11;7:90. doi: 10.3389.

Perroud B, Paymaan J-N, Gatchel JR. Wang L, Barupal D, Crespo-Barreto J, Fiehn O, Zoghbi HY, Kaddurah-Daouk R. Pharmacometabolomic Signature of Ataxia SCA1 Mouse Model and Lithium Effects. PLoS One; 2013; Aug 2;8(8):e70610. doi: 10.1371.

Kaddurah-Daouk R, McEvoy J, Baillie RA, Lee D, Yao JK, Doraiswamy PM, Krishnan KR. Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Mol Psychiatry; 2007 12(10): 934-945.

Yao JK, Dougherty GG, Reddy RD, Keshavan MS, Montrose DM, Matson WR, Rozen S, Krishnan RR, McEvoy J, Kaddurah-Daouk R. Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Mol Psychiatry; 2009;. 28:1-16.

Patkar AA, Rozen S, Mannelli P, Matson W, Pae CU, Krishnan RR, Kaddurah-Daouk R. Alterations in tryptophan and purine metabolism in cocaine addiction: A metabolomic study. Psychopharmacology; 2009; (Berl) 206(3): 479-489.

Mannelli P, Patkar A, Rozen S, Matson WR, Krishnan R, Kaddurah-Daouk R. Opioid use affects antioxidant activity and purine metabolism: Preliminary results. Hum Psychopharmacol; 2009; 24(8):666-675.

Steffens DC, Jiang W, Krishnan KR, Karoly ED, Mitchell MW, O’Connor CM, Kaddurah-Daouk R. Metabolomic differences in heart failure patients with and without major depression. J Geriatr Psychiatry Neurol; 2010; 23(2):138-146.

Yao JK, Dougherty GG, Reddy RD, Keshavan MS, Montrose DM, Matson WR, McEvoy J, Kaddurah-Daouk R. Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia. PLoS ONE; 2010; 5(3): e9508.

Condray R, Dougherty GG, Keshavan MS, Reddy RD, Haas GL, Montrose DM, Matson WR, McEvoy J, Kaddurah-Daouk R, Yao JK. 3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia. Int J Neuropsychopharmacol.; 2011; 6: 756-767.

Kaddurah-Daouk R, McEvoy J, Baillie R, Zhu H, Yao J, Nimgaonkar VL, Buckley PF, Keshavan MS, Georgiades A, Nasrallah HA. Impaired Plasmalogens in Patients with Schizophrenia. Psychiatry Research; 2012; Aug 15;198(3):347-52.

Yao JK, Condray R, Dougherty GG Jr, Keshavan MS, Montrose DM, Matson WR, McEvoy J, Kaddurah-Daouk, R, Reddy RD. Associations between purine metabolites and clinical symptoms in schizophrenia. PLoS One; 2012;. 7(8):e42165. doi: 10.1371.

Kaddurah-Daouk R, Zhu H, Sharma S, Bogdanov M, Rozen SG, Matson W, Oki NO, Motsinger-Reif AA, Churchill E, Lei Z, Appleby D, Kling MA, Trojanowski JQ, Doraiswamy PM, Arnold SE; Pharmacometabolomics Research Network. Alterations in metabolic pathways and networks in mild cognitive impairment and early Alzheimer’s disease. Translational Psychiatry; 2013; 3:e244. doi: 10.1038/tp.2013.18.

Motsinger-Reif AA, Zhu H, Kling MA, Matson W, Sharma S, Fiehn O, Reif DM, Doraiswamy PM, Trajonowski JQ, Kaddurah-Daouk R, Arnold SE. Combining metabolomic and pathologic biomarkers for discriminating early Alzheimer’s disease from normal cognitive aging. ACTA Neuropathologica Communications; 2013;. 1:28.

McEvoy J, Baillie RA, Zhu H, Buckley P, Keshavan MS, Nasrallah HA, Yao J, and Kaddurah-Daouk R. Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics. PLoS One; 2013; Jul 24; 8(7).doi: 10.1038/clpt.2013.153.