Salivary cortisol awakening levels are reduced in human subjects with intermittent explosive disorder compared with controls

Alejandro D Meruelo; Matthew A Timmins; Michael R Irwin; Emil F Coccaro

doi:10.1016/j.psyneuen.2023.106070

Salivary cortisol awakening levels are reduced in human subjects with intermittent explosive disorder compared with controls

Psychoneuroendocrinology. 2023 May:151:106070. doi: 10.1016/j.psyneuen.2023.106070. Epub 2023 Feb 22.

Authors

Alejandro D Meruelo¹, Matthew A Timmins², Michael R Irwin³, Emil F Coccaro⁴

Affiliations

¹ Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
² Clinical Neuroscience and Psychotherapeutics Research Unit, Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
³ Department of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, USA.
⁴ Clinical Neuroscience and Psychotherapeutics Research Unit, Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address: emil.coccaro@osumc.edu.

PMID: 36863129
PMCID: PMC10262314 (available on 2024-05-01)
DOI: 10.1016/j.psyneuen.2023.106070

Abstract

Background: The role of the hypothalamic-pituitary-adrenal (HPA) axis in human aggressive behavior is poorly characterized, though some studies report that, unlike depression, circulating or salivary levels of cortisol are low compared with controls.

Methods: In this study, we collected three salivary cortisol levels (two in the morning and one in the evening) on three separate days in 78 adult study participants with (n = 28) and without (n = 52) prominent histories of impulsive aggressive behavior. Plasma C-Reactive Protein (CRP) and Interleukin-6 (IL-6) were also collected in most study participants. Aggressive study participants meet DSM-5 criteria for Intermittent Explosive Disorder (IED) while non-aggressive participants either had a history of a psychiatric disorder or no such history (Controls).

Results: Morning, but not evening, salivary cortisol levels were significantly lower in IED (p < 0.05), compared with control, study participants. In addition, salivary cortisol levels correlated with measures of trait anger (partial r = -0.26, p < 0.05) and aggression (partial r = -0.25, p < 0.05) but not with measures of impulsivity, psychopathy, depression, history of childhood maltreatment, or other tested variables that often differ in individuals with IED. Finally, plasma CRP levels correlated inversely with morning salivary cortisol levels (partial r = -0.28, p < 0.05); plasma IL-6 levels showed a similar, though not statistically significant (r_p = -0.20, p = 0.12) relationship with morning salivary cortisol levels.

Conclusion: The cortisol awakening response appears to be lower in individuals with IED compared with controls. In all study participants, morning salivary cortisol levels correlated inversely with trait anger, trait aggression, and plasma CRP, a marker of systemic inflammation. This suggests the present of a complex interaction between chronic-low level inflammation, the HPA axis, and IED that warrants further investigation.

Keywords: Aggression; C-reactive protein; Cortisol; IED; Impulsivity.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Aggression / physiology
Disruptive, Impulse Control, and Conduct Disorders*
Humans
Hydrocortisone*
Hypothalamo-Hypophyseal System
Inflammation
Interleukin-6
Pituitary-Adrenal System
Research Subjects

Substances

Hydrocortisone
Interleukin-6

Abstract

Publication types

MeSH terms

Substances

Grants and funding