Traumatic stress results in hypothalamic pituitary adrenal (HPA) axis abnormalities and an increased risk to both suicidal behaviors and post-traumatic stress disorder (PTSD). Previous work out of our laboratory identified SKA2 DNA methylation associations with suicidal behavior in the blood and brain of multiple cohorts. Interaction of SKA2 with stress predicted suicidal behavior with ~80% accuracy. SKA2 is hypothesized to reduce the ability to suppress cortisol following stress, which is of potentially high relevance in traumatized populations. Our objective was to investigate the interaction of SKA2 and trauma exposure on HPA axis function, suicide attempt and PTSD. SKA2 DNA methylation at Illumina HM450 probe cg13989295 was assessed for association with suicidal behavior and PTSD metrics in the context of Child Trauma Questionnaire (CTQ) scores in 421 blood and 61 saliva samples from the Grady Trauma Project (GTP) cohort. Dexamethasone suppression test (DST) data were evaluated for a subset of 209 GTP subjects. SKA2 methylation interacted with CTQ scores to predict lifetime suicide attempt in saliva and blood with areas under the receiver operator characteristic curve (AUCs) of 0.76 and 0.73 (95% confidence interval (CI): 0.6–0.92, P=0.003, and CI: 0.65–0.78, P<0.0001) and to mediate the suppression of cortisol following DST (β=0.5±0.19, F=1.51, degrees of freedom (df)=12/167, P=0.0096). Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.

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Objective The pediatric emergency department (ED) is a critical location for the identification of children and adolescents at risk for suicide. Screening instruments that can be easily incorporated into clinical practice in EDs to identify and intervene with patients at increased suicide risk is a promising suicide prevention strategy and patient safety objective. This study is a retrospective review of the implementation of a brief suicide screen for pediatric psychiatric ED patients as standard of care. Methods The ASQ (Ask Suicide Screening Questions) was implemented in an urban pediatric ED for patients with psychiatric presenting complaints. Nursing compliance rates, identification of at-risk patients and sensitivity for repeated ED visits were evaluated using medical records from 970 patients. Results ASQ was implemented with a compliance rate of 79%. 53% of the patients who screened positive (237/448) did not present to the ED with suicide-related complaints. These identified patients were more likely to be male, African American and have externalizing behavior diagnoses. The ASQ demonstrated a sensitivity of 93% and specificity of 43% to predict return ED visits with suicide-related presenting complaints within six months of the index visit. Conclusions Brief suicide screening instruments can be incorporated into standard of care in pediatric ED settings. Such screens can identify patients who do not directly report suicide-related presenting complaints at triage and who may be at particular risk for future suicidal behavior. Results have the potential to inform suicide prevention strategies in pediatric EDs.