The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia

Biol Psychiatry. 2019 Jan 1;85(1):25-34. doi: 10.1016/j.biopsych.2018.06.015. Epub 2018 Jun 28.


Background: Transcript levels for cytokines and the viral restriction factor interferon-induced transmembrane protein are markedly higher in the prefrontal cortex in schizophrenia. These gene products are regulated by the nuclear factor-κB (NF-κB) transcriptional complex. NF-κB activity, which requires the formation of NF-κB family member heterodimers, is regulated by activation receptors, kinases, and inhibitors. Whether any of these factors are altered in schizophrenia is not known. It is also unclear whether NF-κB-related disturbances reflect ongoing cortical immune activation or a long-lasting response to a prenatal immune-related insult.

Methods: Transcript levels for NF-κB pathway markers were assessed using quantitative polymerase chain reaction in the prefrontal cortex from 1) 62 matched pairs of schizophrenia and unaffected comparison subjects, 2) antipsychotic-exposed monkeys, and 3) adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant polyinosinic-polycytidylic acid.

Results: In schizophrenia subjects, but not antipsychotic-exposed monkeys, we found higher messenger RNA levels for 1) most NF-κB family members, 2) all NF-κB activation receptors, 3) several kinases, and 4) one inhibitor (IκBα) whose transcript level is itself regulated by NF-κB activity. A similar pattern of elevated NF-κB-related messenger RNA levels was seen in adult mice that received daily polyinosinic-polycytidylic acid injections, but not in adult mice subjected to maternal immune activation in utero.

Conclusions: Higher NF-κB activity, evidenced by elevated transcript levels for NF-κB family members, activation receptors, and kinases, may contribute to increased markers of cortical immune activation in schizophrenia.

Keywords: Cytokine; Inflammation; Maternal immune activation; Microglia; NF-κB; Postmortem; Prefrontal cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Animals
  • Antipsychotic Agents / therapeutic use
  • Case-Control Studies
  • Cytokines / blood*
  • Female
  • Humans
  • Macaca fascicularis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • NF-kappa B / blood*
  • Prefrontal Cortex / immunology
  • Pregnancy
  • RNA, Messenger / blood
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*
  • Signal Transduction


  • Antipsychotic Agents
  • Cytokines
  • NF-kappa B
  • RNA, Messenger