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

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 in-dividuals 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 (rp =-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.

Automated summary

This study found that morning salivary cortisol levels were significantly lower in individuals with Intermittent Explosive Disorder (IED) compared with controls. Salivary cortisol levels were inversely correlated with trait anger, trait aggression, and plasma C-Reactive Protein (CRP), a marker of systemic inflammation. This suggests a complex interaction between chronic-low level inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, and IED.