High concentrations of serum interleukin-6 and interleukin-8 in patients with bipolar disorder.

Immune system dysregulation plays a key role in the physiopathology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether interleukins might be biomarkers to distinguish these 2 affective disorders is unclear. Here, we assessed the differences in serum levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) as well as C-reactive protein (CRP) in patients with MDD and BD. In total, we enrolled 21 MDD patients, 26 BD patients, and 20 healthy controls. We collected a total of 35 samples from BD patients in 3 different phases, depression phase, manic phase, and remission stage, and 27 samples from MDD patients in acute and remission phases. Serum IL-6 and IL-8 levels were assessed with solid phase sandwich ELISA-based quantitative arrays, and CRP levels were determined with an automatic analyzer. Both serum IL-6 and IL-8 levels were elevated in BD patients but not MDD patients. Subgroup analysis indicated elevated serum IL-6 in both the depression and manic phases in BD patients. The serum CRP levels did not change in either BD or MDD patients. However, sex differences in CRP concentrations were observed in healthy controls. Furthermore, there were linear correlations between the CRP levels and Bech-Rafaelsen Mania Rating Scale (BRMS) scores in BD patients. IL-6 and IL-8 levels may serve as biomarkers to differentiate between MDD and BD patients, even when the clinical manifestations are atypical. IL-6 may be used for the differential diagnosis of MDD and depressive episodes in BD.

The changes in, and relationship between, plasma nitric oxide and corticotropin-releasing hormone in patients with major depressive disorder.

There is strong evidence of roles of the hypothalamus-pituitary-adrenal axis and nitric oxide (NO) synthase-NO system in depression, but the relationship between them is unknown. The aim of this study, therefore, was to elucidate whether there is any correlation between NO and corticotropin-releasing hormone (CRH) in major depressive disorder (MDD) patients. In 16 outpatients with MDD and 18 healthy controls, the plasma amino acids citrulline (Cit) and arginine (Arg) were determined by high-performance liquid chromatography, and CRH levels was measured by radioimmunoassay. The Cit/Arg ratio was calculated as an index of NO synthesis. Correlations between NO and CRH were examined with the Spearman test. Before treatment, no significant correlation was observed between the plasma NO level and CRH levels in MDD patients. The plasma NO levels were significantly higher in MDD patients. A significant correlation was found between NO levels and Hamilton Depression Rating Scale (HAMD) scores in MDD patients. The plasma CRH levels were significantly higher in MDD patients than in controls. After monotherapy for 2 months, the NO levels had dramatically declined but were also higher than those in the controls. This study is the first report of the absence of a significant correlation between plasma NO and CRH levels, although both levels are elevated in MDD patients. Furthermore, the strong links between the plasma NO levels and the HAMD scores, as well as the increased NO reduction after remission, suggest that NO plays a key role in depression and may be an indicator of therapeutic success.