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Inflammatory cytokines and nuclear factor-kappa B activation in adolescents with bipolar and major depressive disorders.

ABSTRACT: UNLABELLED:Adults with bipolar disorder (BD) and major depressive disorder (MDD) have higher circulating levels of proinflammatory cytokines than healthy controls. However, it is not known whether pediatric-onset patients with BD or MDD show increases in levels of inflammation or activation of nuclear factor kappa B (NF-?B), a key transcription factor in inflammatory signaling. Circulating levels of inflammatory cytokines, as well as spontaneous and stimulated levels of activated NF-?B in total peripheral blood mononuclear cells, monocytes and lymphocytes were measured in adolescents with BD (n=18), MDD (n=13), or no psychiatric history (n=20). Participants had a range of mood symptoms at time of testing. Adolescents with BD had significantly higher spontaneous levels of NF-?B in peripheral blood mononuclear cells, monocyte and lymphocyte populations, and higher plasma levels of IL-1? than healthy controls. Following stimulation with recombinant human TNF-?, participants with BD and MDD both had greater increases in NF-?B in monocytes than controls. Further, greater stimulated increases of NF-?B in monocytes were associated with the current severity of depressive symptoms. The results are limited by the small sample and cross-sectional design. Interventions that target early immunological dysregulation should be examined in relation to long-term outcomes in youth with bipolar and depressive disorders. CLINICAL TRIAL REGISTRATION INFORMATION:Early Intervention for Youth at Risk for Bipolar Disorder, https://clinicaltrials.gov/ct2/show/NCT01483391.

SUBMITTER: Miklowitz DJ

PROVIDER: S-EPMC4912920 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Inflammatory cytokines and nuclear factor-kappa B activation in adolescents with bipolar and major depressive disorders.

Miklowitz David J DJ Portnoff Larissa C LC Armstrong Casey C CC Keenan-Miller Danielle D Breen Elizabeth C EC Muscatell Keely A KA Eisenberger Naomi I NI Irwin Michael R MR

Psychiatry research 20160507

<h4>Unlabelled</h4>Adults with bipolar disorder (BD) and major depressive disorder (MDD) have higher circulating levels of proinflammatory cytokines than healthy controls. However, it is not known whether pediatric-onset patients with BD or MDD show increases in levels of inflammation or activation of nuclear factor kappa B (NF-κB), a key transcription factor in inflammatory signaling. Circulating levels of inflammatory cytokines, as well as spontaneous and stimulated levels of activated NF-κB i ...[more]

PMID: 27227701

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Project description:Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.

Dataset Information

Inflammatory cytokines and nuclear factor-kappa B activation in adolescents with bipolar and major depressive disorders.

Publications

Inflammatory cytokines and nuclear factor-kappa B activation in adolescents with bipolar and major depressive disorders.

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