This Mentored Patient-Oriented Career Development Award (K23) application is designed to advance the candidate?s long-term goal of becoming an independent clinical scientist to improve the treatment of aggression, a major public health problem. Exposure to trauma is common in the general population and is a risk factor for the development of a range of psychopathology, including posttraumatic stress disorder (PTSD). PTSD is associated with an increased propensity toward aggression. Individuals with PTSD show hyperresponsivity to threatening stimuli. These individuals also show increased responsivity in brain regions associated with emotional reactivity and decreased responsivity in brain regions supporting emotion regulation during exposure to negatively-valenced and threatening stimuli. There is also evidence that inhibitory mechanisms are impaired in PTSD as well as evidence for abnormal brain functioning during tasks that require cognitive control. It is unclear, however, to what extent these emotional and cognitive control processes are related to aggression in PTSD, and whether these relationship are mediated through neural mechanisms. The proposed research aims to characterize the neural circuitry of aggression in response to provocation in 150 individuals from the community who vary in PTSD symptom severity. Participants will complete a behavioral aggression task while situated in an MRI scanner. In the course of the task the participant will be interpersonally provoked with a threat of shock by a (fictitious) confederate, and will have the opportunity to retaliate. The purpose of the task is to permit modeling of the blood oxygen level dependent (BOLD) activity related to (1) the neural response to direct interpersonal threat and (2) the neural correlates related to the decision to retaliate. The overarching purpose of the proposed study is to test whether the relationship between PTSD symptoms and aggression are mediated through neural mechanisms related to provocation (implicating emotional reactivity) and/or neural mechanisms related to retaliation (implicating emotion regulation and cognitive control mechanisms). The overall goal of the application is to receive additional training that will prepare Dr. Fanning for an independent career in the translational neuroscience of aggression. In order to meet this long-term goal, training aims will include developing a program of research in the neuroscience of aggression, training in fMRI design and analysis, and advanced statistical training.
Exposure to trauma is common in the general population and is a risk factor for the development of psychopathology, including posttraumatic stress disorder (PTSD) and aggressive behavior. Aggression is a destructive behavior that places a heavy public health burden on society, not only in human suffering but also in costs associated with medical treatment, disability, lost productivity, and premature death. Understanding how brain circuit functioning plays a role in this relationship is necessary to develop effective treatments to reduce aggression that develops or worsens following traumatic exposure.
