Relationship between clinical features and inflammation‐related monocyte gene expression in bipolar disorder – towards a better understanding of psychoimmunological interactions

Abstract

Our hypothesis that lifetime psychotic features would be associated with pro-inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro-inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood-regulating medications.

The effect of mood-stabilizing drugs on cytokine levels in bipolar disorder: A systematic review

“…Lithium has been proposed to exert its immunomodulatory role at the gene expression level. Several researchers have described downregulation of proinflammatory gene expression after treatment with lithium in both patients with BD (Haarman et al, 2014;Padmos et al, 2008) and HCs (Watanabe et al, 2014). Other possible mechanisms are the effects of lithium on different intracellular signaling pathways.…”

“…Included studies are characterized by a broad heterogeneity regarding several potentially confounding factors: demographic characteristics, mood state, symptom severity, duration of medication-free period or duration of mood-stabilizing drug use, concomitant drug use, illness duration and comorbidities among others. Many of these factors are known to influence cytokine levels (Haack et al, 1999;Haarman et al, 2014;O'Connor et al, 2009). Moreover, methodological differences such as sample type (plasma vs. serum) and cytokine assay type (enzyme-linked immunosorbent assay vs. enzyme immunoassay vs. flow cytometry) further increase heterogeneity (Leng et al, 2008;Zhou et al, 2010).…”

“…According to this hypothesis, excessive production of cytokines due to chronic activation of macrophages, microglia, and T-cells is suggested to cause psychiatric signs and symptoms through effects on neurotransmission, neuroendocrine function and neural plasticity (Beumer et al, 2012;Haarman et al, 2014;Maes et al, 1995b;Miller et al, 2009;Rosenblat et al, 2014).…”

Exaggerated Increases in Microglia Proliferation, Brain Inflammatory Response and Sickness Behaviour upon Lipopolysaccharide Stimulation in Non-Obese Diabetic Mice

“…Nevertheless, increasing evidence suggests that chronic mild inflammation of the brain may play a critical role in their development. A link between pro-inflammatory monocyte activation, microglial activation and mood disorders has been shown, at least in a subset of patients [21,22,23,24,25]. …”

Evidence of neuroinflammation in subgroups of schizophrenia and mood disorder patients: A semiquantitative postmortem study of CD3 and CD20 immunoreactive lymphocytes in several brain regions

“…multiple sclerosis, myasthenia gravis, rheumatoid arthritis, lupus erythematosus) as well as the close epidemiological association between autoimmune diseases and psychosis and depression (Benros et al, 2013) suggest similar pathogenetic mechanisms. Moreover, alterations in peripheral immune cells such as T-and B-lymphocytes and of various cytokines have been described in psychotic patients (Debnath & Berk, 2014;Drexhage et al, 2011;Manu et al, 2014;Miller, Gassama, Sebastian, Buckley, & Mellor, 2013;Müller, Weidinger, Leitner, & Schwarz, 2015;Steiner et al, 2010;Tomasik, Rahmoune, Guest, & Bahn, 2014), in patients suffering from major depressive disorder (Raison & Miller, 2013;Setiawan et al, 2015) and in mania (Dickerson et al, 2013;Haarman et al, 2014). In the cerebrospinal fluid (CSF) of patients from the affective and schizophrenia spectrum, subgroups of patients with abnormal immune responses were identified suggesting blood-CSF barrier dysfunction (Bechter et al, 2010;Endres et al, 2015).…”