The role of substance use, smoking, and inflammation in risk for suicidal behavior

•Smoking has the strongest association with aggression, impulsivity, and poor sleep.•Smoking is associated with increased inflammation.•Inflammation is associated with aggression and impulsivity.•Smoking may increase risk for suicidal behavior through inflammatory pathways. Alcohol and substance use disorders are important predictors for suicidal behavior. However, the role of individual substances as proximal risk factors for suicidal behavior and the mechanisms through which substance use affect risk are not entirely clear. We examine whether the frequency of substance use and whether biological markers in the HPA axis and inflammatory pathways are associated with clinical risk factors of suicidal behavior of aggression, impulsivity, hopelessness, and poor sleep. The sample consisted of psychiatric inpatients, aged 15–30 years, admitted for suicide attempt (n = 38), suicidal ideation (n = 40); and healthy controls (n = 37). We measured hair cortisol concentrations, glucocorticoid receptor (GR) sensitivity, stimulated production of interleukin- or IL-6, C-reactive protein, and mRNA expression of GR, SKA2, FKBP5, TNF-α, and IL-1β. Smoking was associated with increased aggression [β = 2.9, 95% CI (–0.03, 6), p = 0.05], impulsivity [β = 3.1, 95% CI (1.6, 4.6), p