TY - JOUR

T1 - A role for prostaglandins in rapid cycling suggested by episode-specific gene expression shifts in peripheral blood mononuclear cells

T2 - a preliminary report

AU - Gurvich, Artem

AU - Begemann, Martin

AU - Dahm, Liane

AU - Sargin, Derya

AU - Miskowiak, Kamilla

AU - Ehrenreich, Hannelore

N1 - © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2014/12

Y1 - 2014/12

N2 - OBJECTIVES: 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.

AB - OBJECTIVES: 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.

KW - Aged

KW - Antidepressive Agents

KW - Bipolar Disorder

KW - Celecoxib

KW - Cyclooxygenase 2

KW - Cyclooxygenase 2 Inhibitors

KW - Female

KW - Follow-Up Studies

KW - Gene Expression Regulation

KW - Humans

KW - Intramolecular Oxidoreductases

KW - Leukocytes, Mononuclear

KW - Lipocalins

KW - Male

KW - Middle Aged

KW - Pyrazoles

KW - RNA, Messenger

KW - Sulfonamides

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/bdi.12223

DO - 10.1111/bdi.12223

M3 - Journal article

C2 - 24964373

VL - 16

SP - 881

EP - 888

JO - Bipolar Disorders (English Edition, Online)

JF - Bipolar Disorders (English Edition, Online)

SN - 1399-5618

IS - 8

ER -