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

International Journal of Bipolar Disorders, Sep 2015

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.

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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 - 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 © 2015 Becking et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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)


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K. Becking, B. C. M. Haarman, R. F. Riemersma van der Lek, L. Grosse, W. A. Nolen, S. Claes, H. A. Drexhage, R. A. Schoevers. Inflammatory monocyte gene expression: trait or state marker in bipolar disorder?, International Journal of Bipolar Disorders, 2015, pp. 20, Volume 3, Issue 1, DOI: 10.1186/s40345-015-0037-x