title: Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains.
abstract: BACKGROUND
  Identification of biomarkers that establish diagnosis or treatment response is critical to the advancement of research and management of patients with depression.
  
  
  OBJECTIVE
  Our goal was to identify biomarkers that can potentially assess fluoxetine response and risk to poor treatment outcome.
  
  
  METHODS
  We measured behavior, gene expression, and the levels of 36 neurobiochemical analytes across a panel of genetically diverse mouse inbred lines after chronic treatment with water or fluoxetine.
  
  
  RESULTS
  Glyoxylase 1 (GLO1) and guanine nucleotide-binding protein 1 (GNB1) mostly account for baseline anxiety-like and depressive-like behavior, indicating a common biological link between depression and anxiety. Fluoxetine-induced biochemical alterations discriminated positive responders, while baseline neurobiochemical differences differentiated negative responders (p < 0.006). Results show that glial fibrillary acidic protein, S100 beta protein, GLO1, and histone deacetylase 5 contributed most to fluoxetine response. These proteins are linked within a cellular growth/proliferation pathway, suggesting the involvement of cellular genesis in fluoxetine response. Furthermore, a candidate genetic locus that associates with baseline depressive-like behavior contains a gene that encodes for cellular proliferation/adhesion molecule (Cadm1), supporting a genetic basis for the role of neuro/gliogenesis in depression.
  
  
  CONCLUSIONS
  We provided a comprehensive analysis of behavioral, neurobiochemical, and transcriptome data across 30 mouse inbred strains that has not been accomplished before. We identified biomarkers that influence fluoxetine response, which, altogether, implicate the importance of cellular genesis in fluoxetine treatment. More broadly, this approach can be used to assess a wide range of drug response phenotypes that are challenging to address in human samples.
authors: Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Genetic Medicine Building, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.
authors: Cristina S
authors: CS
authors: Benton
authors: Brooke H
authors: BH
authors: Miller
authors: Sean
authors: S
authors: Skwerer
authors: Oscar
authors: O
authors: Suzuki
authors: Laura E
authors: LE
authors: Schultz
authors: Michael D
authors: MD
authors: Cameron
authors: J S
authors: JS
authors: Marron
authors: Mathew T
authors: MT
authors: Pletcher
authors: Tim
authors: T
authors: Wiltshire
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005819:Genetic Markers; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D005473:Fluoxetine; D005819:Genetic Markers; D017367:Selective Serotonin Reuptake Inhibitors