Gene expression in peripheral blood mononuclear cells in impulsive aggression: Intermittent explosive disorder compared with non-aggressive healthy and psychiatric controls. (February 2022)

• Record Type: Journal Article
• Authors: Coccaro, Emil F.; Irwin, Michael; Arevalo, Jesusa M.G.; Dizon, Thomas; Cole, Steven
• Is Part Of: Psychoneuroendocrinology. Volume 136(2022)
• Publication Date: 2022-02
• Subjects: Inflammation -- Stress -- Aggression -- IED -- Gene expression; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2021.105453
• Languages: English
• ISSNs: 0306-4530

Abstract

Abstract: Evidence of chronic, systemic, low levels of inflammation is present in several stress-related psychiatric conditions including schizophrenia, depression, and intermittent explosive disorder (IED). We analyzed leukocyte gene expression (mRNA) to quantify the activity of pro and anti-inflammatory signaling pathways. Work performed in non-aggressive populations has uncovered a Conserved Transcriptional Response to Adversity (CTRA) characterized by an upregulation of pro-inflammatory gene transcription in chronically stressed individuals. We used pathway-based bioinformatic analyses of genome-wide transcriptional profiles of peripheral blood leukocyte samples from IED study participants (N = 45) and controls [healthy (n = 45) and psychiatric (n = 34)], with analyses focusing on the pro-inflammatory transcription control pathway mediated by the NF-kB family of transcription factors (typically upregulated in CTRA) and the antiviral transcription control pathway mediated by anti-viral response (IRF) family transcription factors (typically downregulated in CTRA). Compared with both healthy and psychiatric controls, individuals with IED had upregulated transcriptional activity of the antiviral response (IRF), but no evidence of pro-inflammatory NF-kB activation. Analyses implicated CD4 + T cells, CD8 + T cells, and B lymphocytes in IED-related transcriptional alterations, but showed no significant indication of monocyte involvement. This suggests that the inflammatory profile of IED differs substantially from that observed previously in other stress-related disorders, and may involve a pathogen-driven adaptive immune etiology. Highlights: Low levels of inflammation are present in several stress-related psychiatric conditions including those with recurrent impulsive aggression. Leukocyte gene expression (mRNA) assessed activity of pro-/anti-inflammatory pathways in aggressive and non-aggressive individuals. Compared with controls, aggressive individuals had upregulated activity for antiviral response but not for pro-inflammatory NF-kB activation. The inflammatory profile of aggressive individuals differs from that in other disorders, possibly involving a pathogen-driven immune etiology.