title: Peripheral fibroblast metabolic pathway alterations in juvenile rhesus monkeys undergoing long-term fluoxetine administration.
abstract: We report on biochemical pathways perturbed upon chronic fluoxetine administration to juvenile macaques using global metabolomics analyses of fibroblasts derived from skin biopsies. After exposure to tissue culture conditions confounding environmental factors are eliminated and identification of metabolites whose levels are affected by the drug become apparent with a better signal-to-noise ratio compared to data obtained from plasma and cerebrospinal fluid (CSF). Levels of more than 200 metabolites were analyzed to interrogate affected molecular pathways and identify biomarkers of drug response. In addition, we have correlated the metabolomics results with monoamine oxidase (MAOA) genotype and impulsivity behavioral data. Affected pathways include Purine and Pyrimidine metabolisms that have been previously implicated to contribute to neuropsychiatric disorders.
authors.affiliation: Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Su
authors.affiliation: California National Primate Research Center, University of California, Davis, USA.
authors.forename: Casey E
authors.initials: CE
authors.lastname: Hogrefe-Phi
authors.affiliation: Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
authors.affiliation: Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. Electronic address: turck@psych.mpg.de.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, USA. Electronic address: msgolub@ucdavis.edu.
authors.forename: Mari S
authors.initials: MS
authors.lastname: Golub
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002478:Cells, Cultured; D015331:Cohort Studies; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D007175:Impulsive Behavior / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D008995:Monoamine Oxidase / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism
chemical_list: D054316:Biomarkers, Pharmacological; D005473:Fluoxetine; D008995:Monoamine Oxidase; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Biomarkers; Fibroblasts; Fluoxetine; Impulsivity; Metabolomics; Neurodevelopmental disorders