The applicant's long-term objective is to develop a research program focusing on understanding biological mechanisms underpinning externalizing behaviors, including those associated with PTSD, in order to facilitate the development of improved strategies to reduce these behaviors. This is consistent with the NIMH's mission to reduce the burden of mental illness. The applicant's medium-term objective is to become an independent, NIH-funded investigator and a recognized expert in neural and endocrine mechanisms implicated in trauma and aggression. The applicant will accomplish this by i) deepening an existing competency in fMRI with advanced functional connectivity methods; ii) broadening an existing competency in conducting clinical research by gaining experience working in a residential treatment facility and by acquiring training in PTSD assessment techniques; and iii) gaining new competency in endocrinology research. PTSD effects an estimated > 21 million Americans and >30% of PTSD patients do not respond to treatment. PTSD may manifest in the brain as increased neural response to threat cues and disrupted neural responses during emotion regulation. Evidence of PTSD may also present in the body; i.e., as high levels of testosterone. The link between testosterone, neural responses and PTSD is poorly understood. A better understanding of the biological mechanisms underpinning PTSD would likely facilitate the development of improved interventions. Thus, this proposal aims to (i) determine the extent to which testosterone responsiveness modulates response to threat cues in youth with PTSD and (ii) determine the extent to which testosterone responsiveness modulates emotion regulation deficits in youth with PTSD. The applicant proposes to accomplish these aims by recruiting 38 adolescent patients with PTSD and 38 comparison adolescents (aged 14-17; half male; controlling for pubertal status) from a large residential treatment program. A counter-balanced repeated-measures design will be employed where participants will complete an fMRI paradigm designed to assess response to threat and emotion regulation following a testosterone manipulation. Pilot data indicates that a testosterone response can be non-invasively elicited by a social challenge paradigm. Participants will complete the fMRI task following this challenge paradigm or following a paradigm designed to reduce T levels. It is anticipated that the proposed study will show the extent to which an increase in T is associated with an increased responsiveness to emotional stimuli and reduced emotion regulation in youth with PTSD. As current intervention strategies for pediatric PTSD do not consider the role of T, these data will be important in the development of novel treatment modalities. The proposed research would take place at Boys Town, Omaha, NE and Iowa State Univ. Participants will be drawn from the approximately 500 youth in residential treatment at Boys Town and scanned using the on- site dedicated research scanner, while the endocrine research would take place at Iowa State.

Public Health Relevance

Posttraumatic Stress Disorder (PTSD) is a disorder with a high economic, social and human cost affecting many Americans, including many adolescents. A large number of individuals do not respond well to treatment, likely because the biological mechanisms of PTSD are not fully understood. The goal of the current study is to define the neural and hormonal mechanisms implicated in PTSD in youth in order to facilitate the development of improved interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH110643-02
Application #
9471854
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Sarampote, Christopher S
Project Start
2017-04-15
Project End
2021-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Father Flanagan's Boys' Home
Department
Type
DUNS #
073136806
City
Boys Town
State
NE
Country
United States
Zip Code
68010
Aloi, Joseph; Blair, Karina S; Crum, Kathleen I et al. (2018) Adolescents show differential dysfunctions related to Alcohol and Cannabis Use Disorder severity in emotion and executive attention neuro-circuitries. Neuroimage Clin 19:782-792
Meffert, Harma; Thornton, Laura C; Tyler, Patrick M et al. (2018) Moderation of prior exposure to trauma on the inverse relationship between callous-unemotional traits and amygdala responses to fearful expressions: an exploratory study. Psychol Med 48:2541-2549
White, Stuart F; Thornton, Laura C; Leshin, Joseph et al. (2018) Looming Threats and Animacy: Reduced Responsiveness in Youth with Disrupted Behavior Disorders. J Abnorm Child Psychol 46:741-754
White, Stuart F; Zhao, Hui; Leong, Kelly Kimiko et al. (2017) Neural correlates of conventional and harm/welfare-based moral decision-making. Cogn Affect Behav Neurosci 17:1114-1128
Thornton, Laura C; Penner, Elizabeth A; Nolan, Zachary T et al. (2017) The processing of animacy information is disrupted as a function of callous-unemotional traits in youth with disruptive behavior disorders. Neuroimage Clin 16:498-506
Hwang, Soonjo; White, Stuart F; Nolan, Zachary T et al. (2014) Neurodevelopmental changes in the responsiveness of systems involved in top down attention and emotional responding. Neuropsychologia 62:277-85