A role for prostaglandins in rapid cycling suggested by episode‐specific gene expression shifts in peripheral blood mononuclear cells: a preliminary report. (25th June 2014)

• Record Type: Journal Article
• Authors: Gurvich, Artem; Begemann, Martin; Dahm, Liane; Sargin, Derya; Miskowiak, Kamilla; Ehrenreich, Hannelore
• Is Part Of: Bipolar disorders. Volume 16:Number 8(2014)
• Page Start: 881
• Page End: 888
• Publication Date: 2014-06-25
• Subjects: Manic-depressive illness -- Periodicals; Depression, Mental -- Periodicals; 616.895
• DOI: 10.1111/bdi.12223
• Languages: English
• ISSNs: 1398-5647

Abstract

<abstract abstract-type="main" id="bdi12223-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bdi12223-sec-0001" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="bdi12223-sec-0002" sec-type="section"> <title>Methods</title> <p>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 (<italic>PTGDS</italic>), aldo‐ketoreductase family 1, member C3 (<italic>AKR1C3</italic>), cyclooxygenase‐2 (PAN means all splice variants) (<italic>COX2</italic><sub><italic>PAN</italic></sub>), prostaglandin‐endoperoxide synthase 2 (<italic>PTGS2</italic>), and purinergic receptor P2X, ligand‐gated ion channel 7 (<italic>P2RX7</italic>).</p> </sec> <sec id="bdi12223-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>PTGDS</italic> in depressive compared to manic phases. Additionally, higher relative expression of <italic>PTGS2/COX2</italic><sub><italic>PAN</italic></sub> 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.</p> </sec> <sec id="bdi12223-sec-0004" sec-type="section"> <title>Conclusions</title> <p>This study supports a role for prostaglandins in rapid cycling and advocates the cyclooxygenase cascade as a treatment target in this condition.</p> </sec> </abstract>