Inflammatory monocyte gene expression: trait or state marker in bipolar disorder?

BACKGROUND: This study aimed to examine whether inflammatory gene expression was a trait or a state marker in patients with bipolar disorder (BD). METHODS: 69 healthy controls (HC), 82 euthymic BD patients and 8 BD patients with a mood episode (7 depressed, 1 manic) were included from the MOODINFLAME study. Six of the eight patients who had a mood episode were also investigated when they were euthymic (6 of the 82 euthymic patients). Of these participants the expression of 35 inflammatory genes was determined in monocytes using quantitative-polymerase chain reaction, of which a total gene expression score was calculated as well as a gene expression score per sub-cluster. RESULTS: There were no significant differences in inflammatory monocyte gene expression between healthy controls and euthymic patients. Patients experiencing a mood episode, however, had a significantly higher total gene expression score (10.63 ± 2.58) compared to healthy controls (p = .004) and euthymic patients (p = .009), as well as when compared to their own scores when they were euthymic (p = .02). This applied in particular for the sub-cluster 1 gene expression score, but not for the sub-cluster 2 gene expression score. CONCLUSIONS: Our study indicates that in BD inflammatory monocyte, gene expression is especially elevated while in a mood episode compared to being euthymic.

The association between immune activation and manic symptoms in patients with a depressive disorder.

Although recent studies have shown that immunological processes play an important role in the pathophysiology of mood disorders, immune activation may only be present in specific subgroups of patients. Our study aimed to examine whether immune activation was associated with (a) the presence of manic symptoms and (b) the onset of manic symptoms during 2 years of follow-up in depressed patients. Patients with a depressive disorder at baseline (N=957) and healthy controls (N=430) were selected from the Netherlands Study of Depression and Anxiety. Assessments included lifetime manic symptoms at baseline and two-year follow up, as well as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at baseline. Within depressed patients, immune activation was not related to the presence or absence of lifetime manic symptoms at baseline. However, CRP levels were strongly elevated in depressed men who developed manic symptoms compared with those who did not develop manic symptoms over 2 years (P<0.001, Cohen's d=0.89). IL-6 and TNF-α were also higher in depressed men with an onset of manic symptoms, but this association was not significant. However, we found that the onset of manic symptoms was particularly high in men with multiple elevated levels of inflammatory markers. Depressed men who developed manic symptoms during follow-up had increased immunological activity (especially CRP) compared with depressed men who did not develop manic symptoms. Further research should explore whether a treatment approach focusing on inflammatory processes may be more effective in this specific subgroup of depressed patients.