title: Cerebrospinal fluid metabolome in mood disorders-remission state has a unique metabolic profile.
abstract: Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the depressed and remitted phases of major depressive disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared against those in healthy controls (n = 18; HC). The rMDD group showed differences in tryptophan and tyrosine metabolism relative to the other groups. The rMDD group also had higher methionine levels and larger methionine-to-glutathione ratios than the other groups, implicating methylation and oxidative stress pathways. The dMDD sample showed nonsignificant differences in the same direction in several of the metabolic branches assessed. The reductions in metabolites associated with tryptophan and tyrosine pathways in rMDD may relate to the vulnerability this population shows for developing depressive symptoms under tryptophan or catecholamine depletion.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA. Kaddu001@mc.duke.edu
authors.forename: Rima
authors.initials: R
authors.lastname: Kaddurah-Daouk
authors.forename: Peixiong
authors.initials: P
authors.lastname: Yuan
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Boyle
authors.forename: Wayne
authors.initials: W
authors.lastname: Matson
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhao Bang
authors.initials: ZB
authors.lastname: Zeng
authors.forename: Hongjie
authors.initials: H
authors.lastname: Zhu
authors.forename: George G
authors.initials: GG
authors.lastname: Dougherty
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Yao
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.forename: Xavier
authors.initials: X
authors.lastname: Guitart
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Carlson
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Carlos
authors.initials: C
authors.lastname: Zarate
authors.forename: Ranga R
authors.initials: RR
authors.lastname: Krishnan
authors.forename: Husseini K
authors.initials: HK
authors.lastname: Manji
authors.forename: Wayne
authors.initials: W
authors.lastname: Drevets
mesh_terms: D000328:Adult; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid*; D053898:Biosynthetic Pathways; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D015999:Multivariate Analysis; D012075:Remission, Spontaneous; D012720:Severity of Illness Index
chemical_list: D015306:Biogenic Monoamines