title: Comparison of brain and blood gene expression in an animal model of negative symptoms in schizophrenia.
abstract: OBJECTIVE
  To investigate the potential of white blood cells as probes for central processes we have measured gene expression in both the anterior cingulate cortex and white blood cells using a putative animal model of negative symptoms in schizophrenia.
  
  
  METHODS
  The model is based on the capability of ketamine to induce psychotic symptoms in healthy volunteers and to worsen such symptoms in schizophrenic patients. Classical fear conditioning is used to assess emotional processing and cognitive function in animals exposed to sub-chronic ketamine vs. controls. Gene expression was measured using a commercially sourced whole genome rat gene array. Data analyses were performed using ANOVA (Systat 11).
  
  
  RESULTS
  In both anterior cingulate cortex and white blood cells a significant interaction between ketamine and fear conditioning could be observed. The outcome is largely supported by our subsequent metagene analysis. Moreover, the correlation between gene expression in brain and blood is about constant when no ketamine is present (r~0.4). With ketamine, however, the correlation becomes very low (r~0.2) when there is no fear, but it increases to ~0.6 when fear and ketamine are both present. Our results show that under normal conditions ketamine lowers gene expression in the brain, but this effect is completely reversed in combination with fear conditioning, indicating a stimulatory action.
  
  
  CONCLUSIONS
  This paradoxical outcome indicates that extreme care must be taken when using gene expression data from white blood cells as marker for psychiatric disorders, especially when pharmacological and environmental interactions are at play.
authors: University Centre of Psychiatry, University Medical Centre Groningen, University of Groningen, The Netherlands. f.j.bosker@umcg.nl
authors: Fokko J
authors: FJ
authors: Bosker
authors: Anatoliy V
authors: AV
authors: Gladkevich
authors: Charmaine Y
authors: CY
authors: Pietersen
authors: Krista A
authors: KA
authors: Kooi
authors: Petra L
authors: PL
authors: Bakker
authors: Frans
authors: F
authors: Gerbens
authors: Johan A
authors: JA
authors: den Boer
authors: Jakob
authors: J
authors: Korf
authors: Gerard
authors: G
authors: te Meerman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D005239:Fear / Q000187:drug effects; D015870:Gene Expression / Q000502:physiology*; D007649:Ketamine / Q000494:pharmacology; D051381:Rats; D012559:Schizophrenia / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D007649:Ketamine