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Reduced mRNA expression of PTGDS in peripheral blood mononuclear cells of rapid cycling bipolar disorder patients compared with healthy control subjects

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BACKGROUND: Disturbances related to the arachidonic acid cascade and prostaglandin metabolism may be involved in the pathophysiology of bipolar disorder, supported by a recent GWAS 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 (PGH2) 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 RT-qPCR. 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 downregulated in rapid cycling bipolar disorder patients in a euthymic (p=0.01), depressive (p=0.04) and manic/hypomanic (p=0.03) 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.

OriginalsprogEngelsk
TidsskriftThe international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
Sider (fra-til)epii: pyu101
ISSN1461-1457
DOI
StatusUdgivet - 7 dec. 2014

ID: 44889228