Depression and Mania Induce Pro-inflammatory Activation of Macrophages Following Application of Serum from Individuals with Bipolar Disorder

OBJECTIVE: Evidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood. This study investigated whether biochemical changes in the serum from BD patients could modulate the phenotype of cultured macrophages. METHODS: Eighteen subjects with BD and five healthy individuals were included in this study. The human monocyte cell line U-937 was activated with phorbol 12-myristate 13-acetate (PMA) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 hours. Gene expression of selected M1 and M2 markers was assessed by quantitative PCR. RESULTS: Macrophages exposed to serum of manic and depressive BD patients displayed an increase of interleukin-1β (6.40±3.47 and 9.04±5.84 vs. 0.23±0.11; p < 0.05) and tumor necrosis factor-α (2.23±0.91 and 2.03±0.45 vs. 0.62±0.24; p=0.002 and p=0.004, respectively) compared to euthymic group (there was no difference between euthymic and controls). In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29±0.20 vs. 1.86±1.61; p=0.006) and CXCL10 expression (0.36±0.15 and 0.86±0.24 vs. 1.83±0.88; p < 0.000 and p=0.04) compared to the euthymia group. CONCLUSION: Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system is involved in the etiology of BD.

Validation of the Korean Version of the Biological Rhythms Interview of Assessment in Neuropsychiatry

OBJECTIVE: The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) is a scale used to clinically evaluate disturbances in biological rhythm. In this study, we aimed to examine the reliability and validity of the Korean version of the BRIAN (K-BRIAN) in a Korean population. METHODS: A total of 181 participants, including 141 outpatients with bipolar disorder (BD; type I, 62; type II, 79) and 40 controls, were recruited. Construct validity was tested by comparing the mean K-BRIAN scores of the BD patients and control subjects. Concurrent validity was tested by evaluating the association between the K-BRIAN and the Morningness-Eveningness Questionnaire (MEQ). RESULTS: The mean K-BRIAN scores of the control subjects and patients with BD differed significantly (p < 0.001). Particularly, the mean K-BRIAN score was considerably lower among control subjects (mean±standard deviation=35.00±8.88) than among patients with BD type I (41.19±12.10) and type II (50.18±13.73). The Cronbach’s alpha for the K-BRIAN was 0.914. The K-BRIAN was found to correlate with the MEQ (r=-0.45, p < 0.001). CONCLUSION: The findings affirm that the K-BRIAN has good construct validity and internal consistency. This suggests that the K-BRIAN can be used to assess biological rhythms in the Korean population, especially for patients with mood disorder.

The Role of BDNF as a Mediator of Neuroplasticity in Bipolar Disorder

The cognitive impairment and neuroanatomical changes that takes place among patients with bipolar disorder (BD) patients has been well described. Recent data suggest that changes in neuroplasticity, cell resilience and connectivity are the main neuropathological findings in BD. Data from differential lines of research converges to the brain-derived neurotrophic factor (BDNF) as an important contributor to the neuroplasticity changes described among BD patients. BDNF serum levels have been shown to be decreased in depressive and manic episodes, returning to normal levels in euthymia. BDNF has also been shown to decrease as the disorder progresses. Moreover, factors that negatively influence the course of BD, such as life stress and trauma have been shown to be associated with a decrease in BDNF serum levels. These findings suggest that BDNF plays a central role in the progression of BD. The present review discusses the role of BDNF as a mediator of the neuroplastic changes that occur in portion with mood episodes and the potential use of serum BDNF as a biomarker in BD.