Depressed suicidal adolescent males have an altered cortisol response to a pharmacological challenge

Dysregulation of the HPA axis and the dysfunction of the central serotonin (5HT) system are the most replicated biomarkers of depression and suicidal ideation and behavior. However, few studies have examined the two systems simultaneously. In this study, cortisol response was measured in depressed adolescents, following the administration of a central serotonin receptor agonist, meta-chlorphenylpiprazine (mCPP). Adolescents with major depression (MDD; n = 44; males = 15, females = 29; mean age ± SD = 15.5 ± 1.5) were divided into two groups: non-suicidal or those who reported passive suicidal ideation (n = 21), and those who had either threatened suicide or engaged in suicidal acts (n = 23). Sequential infusions of normal saline and mCPP were administered, and serial blood samples were collected for cortisol response. A differential time by group pattern of cortisol response following mCPP was found in the entire group (F(6,242) = 2.6, p=0.018). However, this was mostly attributed to males (F(6,73) = 2.3, p = 0.043) who had threatened or engaged in suicidal acts and displayed a higher cortisol response at 10 and 25 min after the infusion of mCPP, which was not affected by the severity of depression. This differential pattern of cortisol secretion in response to a serotonergic agonist may be a biomarker for more severe forms of suicidal ideation and behavior in adolescent males.