title: P2RX7: expression responds to sleep deprivation and associates with rapid cycling in bipolar disorder type 1.
abstract: BACKGROUND
  Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatment-responsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling.
  
  
  OBJECTIVE
  To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients.
  
  
  METHODS
  Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients.
  
  
  METHODS
  Healthy volunteers at the sleep research center, University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish outpatients recruited from specialized psychiatric clinics for bipolar disorder, diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and anonymous blood donor controls (n = 1,044).
  
  
  RESULTS
  P2RX7 RNA levels were significantly increased during sleep deprivation in PBMCs from healthy volunteers (p = 2.3*10(-9)). The P2RX7 rs2230912 _A allele was more common (OR = 2.2, p = 0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the protective rs2230912_G allele (OR = 0.45-0.49, p = 0.003-0.005) was less common, among rapid cycling cases compared to non-rapid cycling bipolar patients and blood donor controls.
  
  
  CONCLUSIONS
  Sleep deprivation increased P2RX7 expression in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A variant was associated with rapid cycling in bipolar disorder. This supports earlier findings of P2RX7 associations to affective disorder and is in agreement with that particularly rapid cycling patients have a more vulnerable diurnal system.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. lena.backlund@sll.se
authors.forename: Lena
authors.initials: L
authors.lastname: Backlund
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.forename: Louise
authors.initials: L
authors.lastname: Frisén
authors.forename: Pernilla
authors.initials: P
authors.lastname: Nikamo
authors.forename: Dzana
authors.initials: D
authors.lastname: Hukic Sudic
authors.forename: Lil
authors.initials: L
authors.lastname: Träskman-Bendz
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
authors.forename: Gunnar
authors.initials: G
authors.lastname: Edman
authors.forename: Marquis P
authors.initials: MP
authors.lastname: Vawter
authors.forename: Urban
authors.initials: U
authors.lastname: Ösby
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000502:physiology*; D012892:Sleep Deprivation; D013548:Sweden
chemical_list: C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7