Immune activation, steroid resistancy and bipolar disorder

Kupka, Ralph; Breunis, M. Nadine; Knijff, Esther M.; Ruwhof, Cindy; Nolen, W.A.; Drexhage, H. A.

doi:10.1034/j.1399-5618.4.s1.29.x

Cited by 21 publications

(11 citation statements)

References 8 publications

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“…40,46 No doubt, however, that the field has been pioneered by Drexhage et al 23 describing a raised number of pro-inflammatory (M1) monocytes in bipolar patients, by several technical means. 47, 48, 49 Thus, our study is the first independent confirmation of an M1 signature in monocytes from peripheral blood mononuclear cells of bipolar patients without medical comorbidities and strengthens the case for the identification of a subgroup of BD patients who may benefit by anti-inflammatory therapies. Altered monocyte cytokine profile can be the result of an immune or inflammatory process occurring in the central nervous system.…”

Section: Discussionsupporting

confidence: 73%

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

et al. 2014

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We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgfβ (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.

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Section: Discussionsupporting

confidence: 73%

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

et al. 2014

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“…A key feature of BD is shifts in mood states, and it has been suggested that immune system activation may vary across mood episodes of different polarity . During depressive episodes, an increase in proinflammatory cytokines, such as IL‐8, CRP and TNF‐α, was significant among patients with BD versus controls; whereas in mania, levels of IL‐6, IL‐8 and TNF‐α were found to be increased, with inconsistent results for IL‐4 . In another study, cytokine levels were compared in depressed, manic and euthymic patients with BD, finding an increase in IL‐2, IL‐4 and IL‐6 levels in mania and only increase of IL‐6 during depression, whereas euthymic patients showed an increase of IL‐4 .…”

Section: Resultsmentioning

confidence: 99%

Role of immunological factors in the pathophysiology and diagnosis of bipolar disorder: Comparison with schizophrenia

Altamura

Buoli

Pozzoli

2013

Psychiatry Clin Neurosci

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Several lines of evidence point to the key role of neurobiological mechanisms and shared genetic background in schizophrenia and bipolar disorder. For both disorders, neurodevelopmental and neurodegenerative processes have been postulated to be relevant for the pathogenesis as well as dysregulation of immuno-inflammatory pathways. Inflammation is a complex biological response to harmful stimuli and it is mediated by cytokines cascades, cellular immune responses, oxidative factors and hormone regulation. Cytokines, in particular, are supposed to play a critical role in infectious and inflammatory processes, mediating the cross-talk between the brain and the immune system; they also possibly contribute to the development of the central nervous system. From this perspective, even though mixed results have been reported, it seems that both schizophrenia and bipolar disorder are associated with an imbalance in inflammatory cytokines; in fact, some of these could represent biological markers of illness and could be possible targets for pharmacological treatments. In light of these considerations, the purpose of the present paper was to provide a comprehensive and critical review of the existing literature about immunological abnormalities in bipolar disorder with particular attention to the similarities and differences with schizophrenia.

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“…IL-1b (OrtizDominguez et al 2007;Knijff et al 2007;Papiol et al 2004;Kupka et al 2002), IL-2 (Ortiz-Dominguez et al 2007;Breunis et al 2003;Liu et al 2004;Boufidou et al 2004), IL-6 (Ortiz-Dominguez et al 2007;Kim et al 2007;Padmos et al 2008;Kupka et al 2002), IL-8 (O'Brien et al 2006), IFNc (Liu et al 2004;Su et al 2002;Kim et al 2004;Boufidou et al 2004) as well as IL-2R (Breunis et al 2003;Tsai et al 2001;Tsai et al 1999;Maes et al 1995;Kupka et al 2002) and IL-6R (Ortiz-Dominguez et al 2007;Maes et al 1995;Rapaport et al 1999), and MDD e.g. IL-1b,, IL-2, IL-6, sIL-6R, IL-8,, TNFa, and interferon-c (IFNc) (Dowlati et al 2010;Miller et al 2009;Marques-Deak et al 2007;Schiepers et al 2005).…”

Section: Altered Cytokine Levelsmentioning

confidence: 99%

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

et al. 2010

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The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for obesity in mood disorder populations (and vice versa) is a consequence of shared pathophysiological pathways. We conducted a PubMed search of all English-language articles with the following search terms: obesity, inflammation, hypothalamic-pituitary-adrenal axis, insulin, cognition, CNS, and neurotransmitters, cross-referenced with major depressive disorder and bipolar disorder. The frequent co-occurrence of mood disorders and obesity may be characterized by interconnected pathophysiology. Both conditions are marked by structural and functional abnormalities in multiple cortical and subcortical brain regions that subserve cognitive and/or affective processing. Abnormalities in several interacting biological networks (e.g. immuno-inflammatory, insulin signaling, and counterregulatory hormones) contribute to the co-occurence of mood disorders and obesity. Unequivocal evidence now indicates that obesity and mood disorders are chronic low-grade pro-inflammatory states that result in a gradual accumulation of allostatic load. Abnormalities in key effector proteins of the pro-inflammatory cascade include, but are not limited to, cytokines/adipokines such as adiponectin, leptin, and resistin as well as tumor necrosis factor alpha and interleukin-6. Taken together, the bidirectional relationship between obesity and mood disorders may represent an exophenotypic manifestation of aberrant neural and inflammatory networks. The clinical implications of these observations are that, practitioners should screen individuals with obesity for the presence of clinically significant depressive symptoms (and vice versa). This clinical recommendation is amplified in individuals presenting with biochemical indicators of insulin resistance and other concurrent conditions associated with abnormal inflammatory signaling (e.g. cardiovascular disease).

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Immune activation, steroid resistancy and bipolar disorder

Abstract: Kupka RW, Breunis MN, Knijff E, Ruwhof C, Nolen WA, Drexhage HA. Immune activation, steroid resistancy and bipolar disorder.   Bipolar Disord 2002: 4(Suppl. 1): 73–74. © Blackwell Munksgaard, 2002

Cited by 21 publications

References 8 publications

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

Role of immunological factors in the pathophysiology and diagnosis of bipolar disorder: Comparison with schizophrenia

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

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Immune activation, steroid resistancy and bipolar disorder

Abstract: Kupka RW, Breunis MN, Knijff E, Ruwhof C, Nolen WA, Drexhage HA. Immune activation, steroid resistancy and bipolar disorder. Bipolar Disord 2002: 4(Suppl. 1): 73–74. © Blackwell Munksgaard, 2002

Cited by 21 publications

References 8 publications

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

Role of immunological factors in the pathophysiology and diagnosis of bipolar disorder: Comparison with schizophrenia

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

Contact Info

Product

Resources

About

Abstract: Kupka RW, Breunis MN, Knijff E, Ruwhof C, Nolen WA, Drexhage HA. Immune activation, steroid resistancy and bipolar disorder.   Bipolar Disord 2002: 4(Suppl. 1): 73–74. © Blackwell Munksgaard, 2002