Peripheral inflammation during abnormal mood states in bipolar I disorder.
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, 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).


CONCLUSIONS
Participants were not followed prospectively across mood states.


CONCLUSIONS
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.
Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 200 Hawkins Drive W278GH, Iowa City, IA 52242-1057, USA; Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 200 Hawkins Drive W278GH, Iowa City, IA 52242-1057, USA; Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA, 52242, USA. Electronic address: jess-fiedorowicz@uiowa.edu.
Jess G
JG
Fiedorowicz
Department of Psychiatry, University of Texas Health Science Center at Houston, Houston, TX, USA.
Alan R
AR
Prossin
Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 200 Hawkins Drive W278GH, Iowa City, IA 52242-1057, USA.
Casey P
CP
Johnson
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 200 Hawkins Drive W278GH, Iowa City, IA 52242-1057, USA; Department of Electrical and Computer Engineering, College of Engineering, The University of Iowa, Iowa City, IA, 52242, USA.
Gary E
GE
Christensen
Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 200 Hawkins Drive W278GH, Iowa City, IA 52242-1057, USA; Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 200 Hawkins Drive W278GH, Iowa City, IA 52242-1057, USA.
Vincent A
VA
Magnotta
Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 200 Hawkins Drive W278GH, Iowa City, IA 52242-1057, USA; Veterans Affairs Hospital Center, Iowa City, IA, USA.
John A
JA
Wemmie
D000328:Adult; D000339:Affect / Q000502:physiology*; D001714:Bipolar Disorder / Q000276:immunology* / Q000523:psychology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
Affect; Bipolar disorder; Inflammation; Neuroimaging