Inflammatory monocyte gene expression: trait or state marker in bipolar disorder?
Becking et al. Int J Bipolar Disord
Inflammatory monocyte gene expression: trait or state marker in bipolar disorder?
K. Becking 0 2 3
B. C. M. Haarman 1 2
R. F. Riemersma van der Lek 0 2 3
L. Grosse 6
W. A. Nolen 2
S. Claes 5
H. A. Drexhage 4
R. A. Schoevers 0 2 3
0 ICPE/UCP/Triade (CC.72), Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University Medical Center Groningen, University of Groningen , PO Box 30001, 9700 RB Groningen , The Netherlands
1 Radiology Morphological Solutions , Berkel en Rodenrijs , The Netherlands
2 Department of Psychiatry, University Medical Center Groningen, University of Groningen , Groningen , The Netherlands
3 ICPE/UCP/Triade (CC.72), Interdisciplinary Center Psychopathology and Emo- tion Regulation (ICPE), University Medical Center Groningen, University of Gro- ningen , PO Box 30001, 9700 RB Groningen , The Netherlands
4 Department of Immunology, Erasmus MC , Rotterdam , The Netherlands
5 Department of Psychiatry, University of Leuven (KU Leuven) , Louvain , Belgium
6 Department of Psychiatry, University of Mün- ster , Münster , Germany
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.
Bipolar disorder; Gene expression; Mood episode; Trait; State
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Background
Disturbances in the immune system have frequently been
reported in bipolar disorder (BD) (Leboyer et al. 2012).
Several meta-analyses found peripheral cytokines to be
raised in patients compared to healthy controls (HC)
(Modabbernia et al. 2013; Munkholm et al. 2013).
However, the results are heterogeneous, with also studies
reporting on normal (Guloksuz et al. 2010) or even lower
cytokine levels (Boufidou et al. 2004) in BD compared to
HC. This may be due to the fact that peripheral cytokines
are strongly influenced by lifestyle and disease factors
(O’Connor et al. 2009). Focusing on the main cellular
producers of these cytokines, such as circulating
monocytes and macrophages, may be a better approach to find
stable markers for BD. Indeed, studies from our group
focusing on gene expression of circulating monocytes
found a discriminating pro-inflammatory gene
expression in BD patients compared to HC (Drexhage et al.
2010; Padmos et al. 2008).
It remains unclear whether these immunological
disturbances are related to the mood state, or are a trait
phenomenon. Most studies compared BD patients to
HC, without differentiating between patients in
different mood states. The few available studies that
examined immune disturbances across mood states found
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significantly higher levels of peripheral inflammatory
markers during a mood episode compared to euthymia
(Barbosa et al. 2014; Brietzke et al. 2009; Cunha et al.
2008; Ortiz-Domínguez et al. 2007; Tsai et al. 2012).
Regarding inflammatory gene expression, our original
hypothesis prior to the study described below was that
monocyte activity might be a diagnostic biomarker for
BD and thus a trait factor. However, in further analysis
of our previous study, we already found the expression
of specific inflammatory genes to be higher in a small
subsample of depressed versus euthymic patients and to
a lesser extent in manic compared to euthymic patients
(Padmos et al. 2008). Furthermore, we reported a
possible relation between a sub-clus (...truncated)