Decreased Prostaglandin D(2) Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors

BACKGROUND: Prostaglandin (PG) D(2) is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD(2) in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD(2) synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD(2) levels in major depressive disorder. METHODS: Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD(2) levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD(2) in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD(2) levels in mice. RESULTS: Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD(2) levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD(2) production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. CONCLUSION: Decreased PGD(2) levels in major depressive disorder are associated with depression-like behaviors.