Childhood trauma cortisol and immune cell glucocorticoid transcript levels are associated with increased risk for suicidality in adolescence

Rising adolescent suicide rates present a growing unmet need. Childhood trauma (CT) has been associated with altered cortisol dynamics and immune cell glucocorticoid reactivity, yet their additive longer-term contributions to later suicide outcomes are less clear. The current study compared CT scores, resting salivary free cortisol and mononuclear cell gene expression levels of the nuclear receptor, subfamily 3, member 1 (NR3C1) coding the glucocorticoid receptor, and its co-chaperons FKBP prolyl isomerase 5 (FKBP5) and KIT Ligand (KITLG), between a cohort of adolescents presenting with a suicidal crisis requiring hospital treatment, and matched healthy controls. Childhood trauma scores and glucocorticoid measures were significantly altered among suicidal adolescents, and CT scores correlated with mononuclear cell glucocorticoid transcripts. Both CT scores and glucocorticoid measures explained substantial additive portions of the variance in adolescent suicidality. Long-term perturbations in cortisol dynamics and immune cell glucocorticoid response elements denote dysregulated immune stress reactivity, and may possess value in prediction and point to modifiable-risk factors in prevention of clinically significant suicidality during the brittle period of adolescence, years after childhood trauma exposure.