Identifying Biobehavioral Predictors and Targeting Mechanisms of Intervention in Adolescent Posttraumatic Stress Disorder

/ABSTRACT. The overall objective of the proposed K23 is to support Dr. Rachel Siciliano in acquiring the skills necessary to become an independent investigator focused on elucidating mechanisms underlying treatment and individual differences corresponding to treatment response in trauma- exposed youth. Trauma-related mental health problems are a major public health problem. Over four million adolescents meet criteria for posttraumatic stress disorder (PTSD) in the U.S., and while evidence-based treatments (EBTs) are effective, up to a quarter of youth do not respond. EBT mechanisms and predictors of EBT components remain largely unknown. EBTs for PTSD include repeated imaginal exposure to trauma- related content, hypothesized to impact distress and PTSD symptoms via shifts in biological reactivity. Further, baseline threat reactivity and emotion regulation characteristics may influence EBT response. The proposed K23 directly addresses critical gaps in understanding how and for whom repeated imaginal exposure is effective in adolescents with trauma-exposure and PTSD symptoms. The goals of the proposed project are to: (1) examine the biobehavioral effects of repeated imaginal exposure and assess psychophysiological change as a potential mechanism of anxiety change; (2) assess baseline threat reactivity and emotion regulation as predictors of exposure task response; and (3) determine if baseline characteristics and exposure task responses relate to PTSD symptoms longitudinally. Dr. Siciliano is a promising candidate with a strong foundation in biobehavioral assessment and trauma-focused treatment but requires additional training. The proposed training plan closely aligns with the research goals and includes: (1) clinical and randomized controlled trials for adolescent PTSD; (2) EEG and EMG acquisition and analysis with data integration techniques; (3) experimental therapeutics, treatment mechanisms, causal inference, and longitudinal statistics; (4) precision medicine approaches and subgroup analyses; and (5) professional development. The rich academic environment at the Medical University of South Carolina and collective expertise of the mentorship team (Drs. Danielson, McTeague, Cisler, Whitfield-Gabrieli, Hayat) are uniquely suited to provide this training. The mentorship team, coursework, seminars, workshops, and conference attendance afforded by the K23 are essential for launching the candidate's independent career as a high impact translational scientist focused on EBT mechanisms and precision medicine advances for trauma-exposed youth. Findings have wide-ranging implications, as imaginal exposure is a central component in multiple interventions, and identifying distinct combinations of baseline characteristics matching onto exposure may improve treatment response predictions, thus advancing more precise interventions. Results from the proposed research will inform the development of future R01 grants targeting specific mechanisms of EBT components and testing if response to those components varies as a function of baseline characteristics or profiles. Project Number: 1K23MH141303-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Rachel Siciliano | Institution: MEDICAL UNIVERSITY OF SOUTH CAROLINA, CHARLESTON, SC | Award Amount: $206,547 | Activity Code: K23 | Study Section: Special Emphasis Panel[ZRG1 BP-R (81)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11372391