Peripheral inflammation during abnormal mood states in bipolar I disorder

•Elevations in TNF-α, its soluble and other macrophage-derived cytokines appear most prominent in abnormal mood states of bipolar disorder.•Magnetic resonance imaging, using T1ρ, does not identify changes in the brain associated with these cytokines.•Longitudinal study is needed to better understand the relationship between cytokines and mood states in bipolar disorder.

BackgroundBipolar 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.MethodsInvestigations 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).ResultsParticipants 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, and 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, and middle frontal gyrus).LimitationsParticipants were not followed prospectively across mood states.ConclusionActivation 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.