title: Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls.
abstract: BACKGROUND
  Depressive Disorders (DD) are a great financial and social burden. Females display 70% higher rate of depression than males and more than 30% of these patients do not respond to conventional medications. Thus medication-refractory female patients are a large, under-served, group where new biological targets for intervention are greatly needed.
  
  
  METHODS
  We used real-time quantitative polymerase chain reaction (qPCR) to evaluate mRNA gene expression from peripheral blood leukocytes for 27 genes, including immune, HPA-axis, ion channels, and growth and transcription factors. Our sample included 23 females with medication refractory DD: 13 with major depressive disorder (MDD), 10 with bipolar disorder (BPD). Our comparison group was 19 healthy, non-depressed female controls. We examined differences in mRNA expression in DD vs. controls, in MDD vs. BPD, and in patients with greater vs. lesser depression severity.
  
  
  RESULTS
  DD patients showed increased expression for IL-10, IL-6, OXTR, P2RX7, P2RY1, and TRPV1. BPD patients showed increased APP, CREB1, NFKB1, NR3C1, and SPARC and decreased TNF expression. Depression severity was related to increased IL-10, P2RY1, P2RX1, and TRPV4 expression.
  
  
  CONCLUSIONS
  These results support prior findings of dysregulation in immune genes, and provide preliminary evidence of dysregulation in purinergic and other ion channels in females with medication-refractory depression, and in transcription and growth factors in those with BPD. If replicated in future research examining protein levels as well as mRNA, these pathways could potentially be used to explore biological mechanisms of depression and to develop new drug targets.
authors.affiliation: Department of Anesthesiology, University of Utah Health Sciences Center, Salt Lake City, UT, USA. eli.iacob@gmail.com.
authors.forename: Eli
authors.initials: E
authors.lastname: Iacob
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Light
authors.forename: Scott C
authors.initials: SC
authors.lastname: Tadler
authors.forename: Howard R
authors.initials: HR
authors.lastname: Weeks
authors.forename: Andrea T
authors.initials: AT
authors.lastname: White
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Hughen
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Vanhaitsma
authors.forename: Lowry
authors.initials: L
authors.lastname: Bushnell
authors.forename: Alan R
authors.initials: AR
authors.lastname: Light
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism; D061218:Depressive Disorder, Treatment-Resistant / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines