Impaired social functioning is a frequent and disabling consequence of trauma-related disorders. Although social withdrawal results in widespread disability in trauma-exposed populations, little is known about the neurobiological mechanisms underlying this dysfunction. In this project, social withdrawal following trauma exposure is conceptualized as resulting from dysregulation within brain reward pathways. The applicant proposes to use a neuroeconomic paradigm, the Trust Task, to probe alterations in social reward functioning in trauma-exposed populations. Possible contributions of a stress peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), implicated in changes in social behavior following stress exposure, will be identified. The central hypothesis is that in trauma-exposed populations, the extent of social withdrawal (decreased social network size) will be predicted by alterations in both Trust Task behavior and abnormal reward-related neural signaling in the ventral striatum, dorsal striatum, and medial prefrontal cortex. This Mentored Patient-Oriented Research Career Development Award combines research and training activities to support the applicant's long-range goal of developing an independent research program applying neuroeconomic paradigms within dimensional models of anxiety and mood disorders. The first training aim is to develop the applicant's expertise in research on trauma and PTSD. This will be supported through intensive mentorship, provided by Isabelle Rosso, Ph.D., an expert on PTSD neurochemistry, and Kerry Ressler, M.D., Ph.D., an expert in the translational neuroscience of PTSD, both of McLean Hospital/ Harvard Medical School (HMS). The second training aim is to develop expertise in fMRI paradigm design and analysis of neuroeconomic data. This will be supported via mentorship by Diego Pizzagalli, Ph.D., an expert in affective neuroscience, and through consultation with Blaise Frederick, Ph.D., an expert on fMRI, both at McLean Hospital/ HMS, as well as through consultation with Read Montague, Ph.D., a neuroeconomics expert at Virginia Tech Carilion Research Institute. The third training aim is to develop expertise in stress neuroendocrinology, including stress peptides and their interactions with ovarian hormones.
This aim will be supported by Dr. Ressler, who originally identified the relationship between PACAP and PTSD in humans. The program of training has been carefully planned to position the applicant for research independency by the end of the award period. The contribution of the proposed research will advance the field by identifying behavioral, neural, and molecular biomarkers for social anhedonia and social withdrawal in trauma-exposed women. By using neuroeconomic paradigms to characterize alterations in reward circuitry that contribute to social withdrawal, the proposed research represents a substantive departure from the status quo. To summarize, the proposed project will provide the applicant with a strong foundation in PTSD research and functional neuroimaging, while also advancing understanding of the neural mechanisms underlying social withdrawal following trauma exposure.
By using a neuroeconomic paradigm to identify neural and molecular targets related to social anhedonia following trauma exposure in women, this research is expected to increase understanding of the mechanisms underlying social withdrawal, a behavior that is strongly associated with health outcomes including increased risk of disability, reduced immune response, increased mortality risk, and suicidality. This work is particularly critical because of the high incidence of trauma exposure in women and the prominent, long-lasting, and costly social deficits that result. This project is relevant to NIMH's mission because it is an example of the identification of biomarkers and behavioral indicators associated with mental disorders (Strategy 1.3), and because it may ultimately result in improvement in the treatment of trauma and stress-related disorders.
| Olson, Elizabeth A; Kaiser, Roselinde H; Pizzagalli, Diego A et al. (2018) Anhedonia in Trauma-Exposed Individuals: Functional Connectivity and Decision-Making Correlates. Biol Psychiatry Cogn Neurosci Neuroimaging 3:959-967 |
