title: A role for prostaglandins in rapid cycling suggested by episode-specific gene expression shifts in peripheral blood mononuclear cells: a preliminary report.
abstract: OBJECTIVE
  Over 12% of patients with bipolar disorder exhibit rapid cycling. The underlying biological mechanisms of this extreme form of bipolar disease are still unknown. This study aimed at replicating and extending findings of our previously published case report, where an involvement of prostaglandin synthesis-related genes in rapid cycling was first proposed.
  
  
  METHODS
  Psychopathological follow-up of the reported case was performed under cessation of celecoxib treatment. In a prospective observational study, patients with bipolar disorder (n = 47; of these, four had rapid cycling) or with monopolar depression (n = 97) were recruited over a period of three years. Repeated psychopathology measurements were conducted using standard instruments. Peripheral blood mononuclear cells (PBMC) were obtained during as many consecutive episodes as possible and processed for mRNA isolation and quantitative real-time reverse transcriptase polymerase chain reaction for prostaglandin D2 synthase (PTGDS), aldo-ketoreductase family 1, member C3 (AKR1C3), cyclooxygenase-2 (PAN means all splice variants) (COX2PAN ), prostaglandin-endoperoxide synthase 2 (PTGS2), and purinergic receptor P2X, ligand-gated ion channel 7 (P2RX7).
  
  
  RESULTS
  The follow-up of our original case of a patient with rapid cycling who had shown impressive psychopathological improvement under celecoxib revealed complete loss of this effect upon discontinuation of the COX2 inhibitor. Episode-specific gene expression measurements in PBMC of four newly recruited rapid cycling patients confirmed the higher expression of PTGDS in depressive compared to manic phases. Additionally, higher relative expression of PTGS2/COX2PAN was found. No comparable alterations were observable in samples available from the remaining 43 patients with bipolar disorder and the 97 monopolar depressed patients, emphasizing the advantages of the rapid cycling condition with its rapid and frequent shifts for identification of gene expression changes.
  
  
  CONCLUSIONS
  This study supports a role for prostaglandins in rapid cycling and advocates the cyclooxygenase cascade as a treatment target in this condition.
authors: Clinical Neuroscience, Max Planck Institute of Experimental Medicine.
authors: Artem
authors: A
authors: Gurvich
authors: Martin
authors: M
authors: Begemann
authors: Liane
authors: L
authors: Dahm
authors: Derya
authors: D
authors: Sargin
authors: Kamilla
authors: K
authors: Miskowiak
authors: Hannelore
authors: H
authors: Ehrenreich
mesh_terms: D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D052246:Cyclooxygenase 2 Inhibitors; D054834:Lipocalins; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000068579:Celecoxib
keywords: aldo-ketoreductase family 1, member C3 (AKR1C3); bipolar disorder; celecoxib; cyclooxygenase 2 (COX2); hibernation; monopolar depression; prostaglandin D2 synthase (PTGDS); prostaglandin synthesis; prostaglandin-endoperoxide synthase 2 (PTGS2); purinergic receptor P2X, ligand-gated ion channel 7 (P2RX7)