title: ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder.
abstract: BACKGROUND
  In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD), has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD.
  
  
  METHODS
  We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class.
  
  
  RESULTS
  These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models
  
  
  CONCLUSIONS
  Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathophysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies - Biology and Genetic Division, University of Brescia, Viale Europa 11, Brescia, 25123, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Milanesi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Minelli
authors.forename: Nadia
authors.initials: N
authors.lastname: Cattane
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cattaneo
authors.forename: Cristina
authors.initials: C
authors.lastname: Mora
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbon
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallei
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Florio
authors.forename: Andreas
authors.initials: A
authors.lastname: Conca
authors.forename: Stefano
authors.initials: S
authors.lastname: Bignotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
mesh_terms: D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020893:Receptor, ErbB-3 / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D012333:RNA, Messenger; C581292:ERBB3 protein, human; C496348:FGFR1 protein, human; D020893:Receptor, ErbB-3; D051496:Receptor, Fibroblast Growth Factor, Type 1