Predicting worsening suicidal ideation with clinical features and peripheral expression of messenger RNA and microRNA during antidepressant treatment

Objective: To investigate how the combination of clinical and molecular biomarkers can predict worsening of suicidal ideation during antidepressant treatment. Methods: Samples were obtained from 237 patients with major depressive disorder (DSM-IV criteria) treated with either duloxetine or placebo in an 8-week randomized controlled trial. Data were collected between 2007 and 2011. The relationship between treatment-worsening suicidal ideation (TWSI) and a number of clinical variables, as well as peripheral expression of messenger RNA (mRNA) and microRNA (miRNA), was assessed at baseline. We generated 4 predictive models for TWSI: clinical, mRNA, miRNA, and a combined model comprising the best predictive variables from clinical, mRNA, and miRNA data. Results: Eleven patients (9.8%) presented with TWSI in the duloxetine group. Among the clinical variables, only baseline depressive severity was found to be mildly predictive of TWSI. Two mRNAs (stathmin 1 [STMN1] and protein phosphatase 1 regulatory subunit 9B [PPP1R9B]) and 2 miRNAs (miR-3688 and miR-5695) were identified that were significantly predictive of TWSI when mRNA and miRNA were assessed separately (P=.002,.044,.004, and.005, respectively). The best model included baseline depression severity and expression of STMN1 and miR-5695 and predicted TWSI with area under the curve = 0.94 (P<.001). Additionally, the combined model did not significantly predict TWSI in the placebo group. Conclusions: This study generated a predictive tool for TWSI that combines both biological and clinical variables. These biological variables can be easily quantified in peripheral tissues, thus rendering them viable targets to be used in both clinical practice and future studies of suicidal behaviors.