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Introduction: Many Veterans with PTSD struggle with symptoms of social dysfunction, including isolation [1] and physical violence [2]. Current Veterans Affairs (VA) treatments effectively decrease posttraumatic stress symptoms (PTSS) [3, 4, 5, 6], but do not directly target social dysfunction. In the current study, we investigate deficits in two potential mechanisms: trust and social responsiveness. We propose to use the iterated Trust Game [7, 8]– an economic exchange task that operationalizes trust and social responsiveness– to investigate differences due to PTSS severity. We will also investigate changes after treatment using the Trust Game in a dataset of Veterans undergoing residential treatment for PTSD at a VA Medical Center. We hypothesize that those with greater PTSS severity will show deficits in trust or social responsiveness, and these deficits will assuage with PTSS improvement after treatment. Methods: We analyze a cross-sectional dataset of combat-exposed Veterans (n = 153) and a dataset undergoing residential treatment for PTSD (n = 36). PTSS are measured using the PTSD CheckList (PCL). Each Veteran plays a ten-round variant of the iterated Trust Game. Each round involves exchange between the Veteran (or “investor”) who is endowed $20 each round, and a “trustee”, in whom the investor may entrust any portion of the $20. The investment is tripled before being sent to the trustee, and the trustee may return any proportion. Trust is operationalized as investment, and social responsiveness is operationalized as the ability of the trustee’s changes in response to the investor—“trustee reciprocity”—to predict changes in the investor’s next round investment. We investigate the two potential mechanisms in the cross-sectional dataset. To determine the relationship between trust and PTSS, we regress investment onto PCL. To investigate the relationship between social responsiveness and PTSS, we regress round change in investment onto the interaction of PCL and trustee reciprocity. We next investigate the impact of treatment in the residential treatment dataset. To determine the impact of PTSS improvement on trust, we regress change in investment onto PCL score change (posttreatment–pretreatment). To determine the impact of treatment-related change on social responsiveness, we regress round change in investment onto the interaction of change in PCL (posttreatment–pretreatment), visit, and trustee reciprocity. Results: In the cross-sectional dataset, higher PTSS correlates with decrease in trust, operationalized as investment (β1 = −0.002, p = 0.003, n = 153). Increase in trustee reciprocity correlates with increase in round change in investment (β1 = −0.25, p < 0.001, n = 153), indicating Veterans were socially responsive. There was no PTSS-related variation in social responsive- ness (0 < β3 < 0.001,p = 0.5,n = 153). In the residential treatment dataset, less PTSS improvement correlated with decrease in trust after treatment (β1 = −0.006, p = 0.015, n = 36). Veterans were socially responsive (β1 = 0.39,p < 0.001,n = 36), with a decrease in responsiveness at posttreatment (β5 = −0.29,p = 0.001, n = 36) and a greater decrease posttreatment in those with less improvement in PTSS (β7 = −0.01, p = 0.02, n = 36). Conclusions: In the cross-sectional dataset, trust decreased with higher PTSS, while social responsiveness did not change with PTSS severity. This suggests that Veterans with more severe PTSS show deficits in trust, but not social responsiveness, and supports deficit trust as a mechanism for the social dysfunction observed in Veterans with PTSD. In the residential treatment dataset, both trust and social responsiveness decreased with less improvement in PTSS after treatment. This suggests that Veterans whose PTSS do not improve with treatment experience further decline in mechanisms of social functioning after discharge. In the absence of a control group, it is hard to determine whether this decline is due to symptom-related order effect, or unsuccessful treatment itself. These findings suggest decreased trust, but not social responsiveness, is a mechanism of social dysfunction observed in PTSD. Further investigation into mechanisms of social dysfunction and treatment-related change in Veterans with PTSD, the iatrogenic effects described, and the way these effects can be minimized is also necessary. These findings lend support to treatments that directly target social dysfunction in the context of treatment-resistant post- traumatic stress disorder. / National Institute of Health, 1I01RX000120, NIH-I01 2009-2010, 2013-2014, NIH-I01 2018-2019 National Institute of Health, 5I01RX002354, NIH-I01 2018-2019, 2020-2021 / Master of Science

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The current study takes an initial step toward deriving a method for empirically based, theory-driven treatment matching in a military population suffering from PTSD. Along with the more overt symptoms of PTSD (e.g., persistent hyperarousal), secondary cognitive symptoms have also been shown to be significantly associated with avoidance and intrusive symptoms, as well as contribute to functional impairment. Based on the factor analytic and treatment literature for PTSD, it appears that there are two central mechanisms associated with beneficial therapeutic change that underlies both CPT and PE treatments (i.e., habituation, changes in cognitions). Additionally, different traumatic events and peritraumatic responses may be associated with unique symptom profiles and may necessitate targeted treatment. The present study proposes a novel approach to treatment matching based on the factor structure of PTSD and underlying mechanisms of treatment response. More broadly, this paper provides evidence for a broader understanding of peritraumatic responses and the potential implications of these responses for symptom profiles and illness trajectories.