title: Reduced mRNA expression of PTGDS in peripheral blood mononuclear cells of rapid-cycling bipolar disorder patients compared with healthy control subjects.
abstract: BACKGROUND
  Disturbances related to the arachidonic acid cascade and prostaglandin metabolism may be involved in the pathophysiology of bipolar disorder, as supported by a recent genome-wide association study meta-analysis; however, evidence from clinical studies on a transcriptional level is lacking. Two enzymes in the arachidonic acid cascade are the prostaglandin D synthase (PTGDS), which catalyzes the conversion of prostaglandin H2 to prostaglandin D2 (PGD2), and the aldo-keto reductase family 1 member C3 (AKR1C3), which catalyzes the reduction of PGD2. We aimed to test the hypothesis that mRNA expression of PTGDS and AKR1C3 is deregulated in rapid-cycling disorder patients in a euthymic or current affective state compared with healthy control subjects, and that expression alters with affective states.
  
  
  METHODS
  PTGDS and AKR1C3 mRNA expression in peripheral blood mononuclear cells was measured in 37 rapid-cycling bipolar disorder patients and 40 age- and gender-matched healthy control subjects using reverse transcription quantitative real-time polymerase chain reaction. Repeated measurements of PTGDS and AKR1C3 mRNA expression were obtained in various affective states during 6-12 months and compared with repeated measurements in healthy control subjects.
  
  
  RESULTS
  Adjusted for age and gender, PTGDS mRNA expression was down-regulated in rapid-cycling bipolar disorder patients in a euthymic, depressive, and manic/hypomanic state compared with healthy control subjects. No difference in PTGDS mRNA expression was observed between affective states. AKR1C3 mRNA expression did not differ between bipolar disorder patients in any affective state or in comparison with healthy control subjects.
  
  
  CONCLUSIONS
  The results suggest a role for aberrantly-regulated PTGDS mRNA expression in rapid-cycling bipolar disorder. The sample size was limited; replication of the findings in larger, independent samples is warranted to further explore the role of the arachidonic acid cascade and prostaglandin metabolism as a potential therapeutic target in bipolar disorder.
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark (Drs Munkholm, Kessing, and Vinberg); Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark (Dr Peijs). klaus.munkholm@regionh.dk.
authors.forename: Klaus
authors.initials: K
authors.lastname: Munkholm
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark (Drs Munkholm, Kessing, and Vinberg); Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark (Dr Peijs).
authors.forename: Lone
authors.initials: L
authors.lastname: Peijs
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark (Drs Munkholm, Kessing, and Vinberg); Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark (Dr Peijs).
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark (Drs Munkholm, Kessing, and Vinberg); Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark (Dr Peijs).
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000339:Affect; D000367:Age Factors; D000368:Aged; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001714:Bipolar Disorder / Q000378:metabolism* / Q000523:psychology*; D016022:Case-Control Studies; D003863:Depression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics*; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
chemical_list: D054834:Lipocalins; D012333:RNA, Messenger; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
keywords: AKR1C3; PTGDS; biomarker; bipolar disorder; rapid cycling