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Plasma and cerebrospinal fluid inflammatory markers and human aggression

Neuropsychopharmacology volume 48, pages 1060–1066 (2023)Cite this article

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Abstract

A growing body of work suggests that individuals with aggressive behavior and/or aggressive tendencies have evidence of chronic, low level, inflammation as manifested by elevated circulating levels of acute phase reactant proteins and pro-inflammatory cytokines. While animal studies report that direct application of pro-inflammatory proteins in brain increase aggressive behavior, there is no data on the relationship of central levels of these proteins and aggression in human subjects. We simultaneously measured levels of both plasma and lumbar cerebrospinal fluid (CSF) C-Reactive Protein (CRP) and IL-6, IL-8, and TNF-α in 77 medically healthy, drug-free, individuals with varying degrees of aggression including 22 individuals with DSM-5 Intermittent Explosive Disorder (IED). Aggression was assessed using the Life History of Aggression (LHA) and the Buss-Perry Aggression Questionnaire (BPAQ). Plasma and CSF levels of CRP, IL-8, and TNF-α, but not IL-6, correlated significantly with each other. Aggressive individuals with IED displayed elevated plasma, but not CSF, levels of proinflammatory markers and this relationship was specific to IED. Similarly, composite aggression scores correlated significantly with plasma, but not CSF, pro-inflammatory markers. Aggressive behavior in humans is correlated with Plasma, but not CSF, proinflammatory markers despite the observation that these two sets of markers are significantly correlated. Since the direct application of proinflammatory proteins in brains of animals increase aggressive behavior, proinflammatory proteins likely influence brain-based behavior in a manner not reflected in lumbar CSF.

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Fig. 1: Plasma/CSF Correlation of CRP and Cytokines.
Fig. 2: Plasma and CSF Pro-Inflammatory Levels as a Function Group.
Fig. 3: Correlation Between COMP Plasama Pro-Inflammatory Level and COMP Aggression/Anger-Hostility/Impulsivity Score.

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Acknowledgements

Alan Klock, M.D. and Robert Fong, M.D. (Department of Anesthesiology and Critical Care at the University of Chicago, Division of Biological Sciences) performed the lumbar punctures.

Funding

This work was supported by a grant from the National Institute of Mental Health: RO1 MH104673 (Dr. Coccaro).

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Authors and Affiliations

  1. Clinical Neuroscience and Psychotherapeutics Research Unit, Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Emil F. Coccaro

  2. Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA

    Royce Lee

  3. Department of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, USA

    Elizabeth C. Breen & Michael R. Irwin

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Contributions

EFC: Conceptualization, Funding Acquisition, Project Management, Data Collection, Statistical Analysis, Writing. RL: Data collection, Writing—review and editing. ECB: Laboratory analysis (assays) and Interpretation of Data. MRI: Conceptualization, Interpretation of Data, and Revising Manuscript Critically for Important Intellectual Content.

Corresponding author

Correspondence to Emil F. Coccaro.

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Competing interests

EFC reports being a consultant to and being on the Scientific Advisory Boards of Azevan Pharmaceuticals, Inc., Avanir Pharmaceuticals, Inc., Boerhinger Ingelheim, Pharma, Inc., and being a current recipient of a grant award from the NIMH and NIAAA. RL, ECB, and MRI report no biomedical financial interests or competing interests.

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Coccaro, E.F., Lee, R., Breen, E.C. et al. Plasma and cerebrospinal fluid inflammatory markers and human aggression. Neuropsychopharmacol. 48, 1060–1066 (2023). https://doi.org/10.1038/s41386-023-01541-3

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