Peripheral inflammation during abnormal mood states in bipolar I disorder

Abstract

Background Bipolar disorder carries a substantive morbidity and mortality burden, particularly related to cardiovascular disease. Abnormalities in peripheral inflammatory markers, which have been commonly reported in case-control studies, potentially link these co-morbidities. However, it is not clear whether inflammatory markers change episodically in response to mood states or are indicative of chronic pro-inflammatory activity, regardless of mood, in bipolar disorder. Methods Investigations focused on comparing concentrations of specific inflammatory cytokines associated with immune activation status (primary outcome = tumor necrosis factor alpha (TNF-α)) in 37 participants with bipolar disorder across 3 mood states (mania N=15, depression N=9, normal mood N=13) and 29 controls without a psychiatric disorder (total N=66). Cytokine levels were also compared to T1ρ, a potential neuroimaging marker for inflammation, in select brain regions in a subsample (N=39). Results Participants with bipolar disorder and healthy controls did not differ significantly in inflammatory cytokine concentrations. However, compared to cases with normal mood, cases with abnormal mood states (mania and depression) had significantly elevated levels of TNF-α, its soluble receptors (sTNFR1/sTNFR2), other macrophage-derived cytokines (interleukin 1β (IL-1β), IL-6, IL-10, IL-18) in addition to IL-4, interferon-γ, monocyte chemotactic protein-1, fibroblast growth factor β, and vascular endothelial growth factor. Cytokine levels were not correlated with signals from T1ρ imaging in selected structures (amygdalae, hippocampi, hypothalamus, anterior cingulate gyrus, middle frontal gyrus). Limitations Participants were not followed prospectively across mood states. Conclusion Activation of inflammatory markers was found in abnormal mood states of bipolar disorder. Longitudinal study of individuals with mood disorders is needed to confirm these findings and to elucidate the time course of any such changes.

Association between Elevated C-Reactive Protein and Manic Polarity in Acute Psychiatric Inpatients with Affective Symptomatology

“…The results show elevated CRP levels in patients hospitalized due to manic exacerbation compared to depressed exacerbation, suggesting that, in affective patients, manic polarity has a stronger link to inflammation compared to depressed polarity. The results of this study concur with recent reports suggesting increased immune activation in bipolar patients compared to non-bipolar patients [2, 3, 7, 9, 16-20], and increased immune activation in manic patients compared both to the non-manic bipolar patients and the non-bipolar patients [9, 14, 15, 17, 21-23]. However, in those studies, patients were selected and categorized based on their DSM diagnoses, while we employed a transdiagnositc approach and included all inpatients with acute affective exacerbation leading to hospitalization, regardless of their primary DSM diagnoses.…”

Bipolar disorder with Marfan syndrome: a case illustration based on possible involvement of TGF-β1 in the common etiopathogenesis

“…Unlikely, a recent meta-analysis showed no significant differences between BPD patients and healthy controls for the levels of TGF-β1 [6]. Two recent studies have not demonstrated elevated TGF-β1 plasma levels in BPD [13,14]. In contrast, another has found TGF-β1 and IL-23 plasma levels significantly higher in BPD [15] (Table 1).…”

Both Serum Brain-Derived Neurotrophic Factor and Interleukin-6 Levels Are Not Associated with Therapeutic Response to Lamotrigine Augmentation Therapy in Treatment-Resistant Depressive Disorder

“…In addition, elevated proinflammatory cytokines are also involved in the pathophysiology of mood disorder [13-15]. Serum interleukin-6 (IL-6) levels among them are increased during depression and are reduced to normal levels after recovery in patients with major depressive disorder [13].…”

“…Serum interleukin-6 (IL-6) levels among them are increased during depression and are reduced to normal levels after recovery in patients with major depressive disorder [13]. In addition, peripheral IL-6 levels are increased in bipolar depression, and its levels approach normal in the euthymic state [14, 15]. This suggests that decreased IL-6 levels are associated with effective treatment of major depressive episodes.…”