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

Abstract

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 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-κB in peripheral blood mononuclear cells, monocyte and lymphocyte populations, and higher plasma levels of IL-1β than healthy controls. Following stimulation with recombinant human TNF-α, participants with BD and MDD both had greater increases in NF-κB in monocytes than controls. Further, greater stimulated increases of NF-κB 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.

Keywords: Inflammation; Inflammatory signaling; Interleukin-1; Lymphocytes; Monocytes; NF-ΚB; Peripheral blood mononuclear cells.