Neuroeconomics of Social Behavior Following Trauma Exposure

Study Overview
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Brief Summary
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This study will use a neuroeconomic paradigm with state-of-the-art imaging protocols to probe abnormal social reward processing underlying social withdrawal in symptomatic trauma-exposed women. By also gathering self-report measures of social anhedonia, performance on non-social and social reward valuation tasks, and measures of real-world social functioning including social network size, we aim to specify how alterations in social reward processing result in social withdrawal and functional impairment.

Detailed Description
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Impaired social functioning is a frequent and disabling sequela of trauma-related disorders. PTSD is associated with a high rate of severe impairment in quality of life relative to other anxiety disorders, including panic disorder, social phobia, and OCD, with particularly marked impairment in social quality of life. Mounting evidence indicates that impairment in quality of life in PTSD is strongly related to its effect on social functioning. Such difficulties are widespread and affect multiple social networks, including marital relationships, and friendships and family relationships. Social withdrawal, defined here in terms of reduced social network size, is of particular interest because of its strong relationship with health outcomes, including increased risk of disability, reduced immune response, and increased mortality risk; most critically, poor social integration is associated with a threefold increase in suicide risk. Because women are at a 2.3-to-3-fold increased risk compared to men of developing PTSD following trauma, understanding the differential neurobiological pathways that may contribute to the development of stress-related disorders in women is particularly critical. Women are more likely than men to endorse social detachment following trauma, especially when the trauma involves exposure to violence. In this project, we propose abnormal reward processing (anhedonia) as a specific mechanism underlying social withdrawal in trauma-exposed women, and we present a paradigm that capitalizes on advances in neuroeconomics to elucidate the neural underpinnings of social withdrawal. Additionally, we propose to identify the possible influences of a stress peptide (pituitary adenylate cyclase-activating polypeptide: PACAP) implicated in sex-specific changes in social behavior following stress exposure.

Official Title
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Social Withdrawal Following Trauma Exposure: a Neuroeconomic Approach

Conditions
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Posttraumatic Stress Disorder

Participation Criteria
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Eligibility Criteria
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Phase 1: Inclusion Criteria: Age 18-45 Self-reported healthy volunteer status Exclusion Criteria: Inability to provide written informed consent in English Inability to see task due to visual impairment Participants who produce T-scores of 65 or higher on any Brief Symptom Inventory (BSI) subscales will not be eligible to remain in the Trust Task participant pool. Phase 2: Inclusion Criteria: Female Trauma exposure appropriate to group For trauma-exposed groups the index trauma is actual or threatened physical assault or sexual violence PCL-5 score 33 and above (for PS-SA and PS-nonSA groups) Right handedness Age 18-45 English as a first language Exclusion Criteria: History of neurological illness (including head injury with loss of consciousness > 5 minutes) Medical conditions that may influence neuroimaging (e.g. HIV) Current or past DSM-5 Axis I disorder (for HC group) History of bipolar disorder or schizophrenia spectrum disorder Contraindications for MRI Alcohol dependence in the past 5 years Substance dependence in the past 3 years Daily substance use in the past year Prescribed psychotropic medication use in the past month Wechsler Abbreviated Scale of Intelligence- Second Edition (WASI-II) FSIQ < 70.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Phase 1<br>Healthy control participants will provide neuroeconomic game responses to form a pool of potential responses for participants to interact with during Phase 2. | |
| Phase 2: PTS-SA<br>posttraumatic spectrum-socially anhedonic | |
| Phase 2: PTS-nonSA<br>posttraumatic spectrum-non-socially anhedonic | |
| Phase 2: HC<br>healthy controls | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group differences in neuroeconomic game performance | Compared to the PTS-nonSA and HC groups, the PTS-SA group will demonstrate lower investments and slower learning rates on the Trust Task than on the non-social risk task compared with PTS-nonSA and HC subjects | Measured on the day of the MRI scan | 
| Group differences in fMRI BOLD signal | The HC and PTS-nonSA groups will show greater ventral striatum (VS), dorsal striatum (DS), and medial prefrontal cortex (mPFC) responses during the outcome phase of the trust game for 'share' versus baseline, compared to the PTS-SA group, for the real partner condition (Trust Task), but not for the risk task. | Measured on the day of the MRI scan | 
| Correlations between behavior and fMRI BOLD signal | Because social withdrawal will occur in response to reduced social reward value, we hypothesize that across the PTS groups, reduced VS, DS, and mPFC activity during the outcome phase of the trust game for 'share' outcomes will be associated with lower Trust Task investments, greater self-reported social anhedonia, and smaller social network size. | Measured on the day of the MRI scan | 
| PACAP correlations | Elevated PACAP levels will be associated with lower investments on the Trust Task; decreased social reward signals during the outcome phase for 'share' outcomes in the VS, DS, and mPFC; and smaller social network size. | Measured on the day of the MRI scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mediation analysis | Within the PTS groups, decreased VS, DS, and mPFC response to 'share' outcomes will mediate the relationship between social anhedonia and reduced social network size. | Measured on the day of the MRI scan | 
| Functional connectivity (psychophysiological interaction) | PTS individuals with higher self-reported social anhedonia and social withdrawal will show reduced VS-mPFC connectivity for social rewards on the Trust Task. | Measured on the day of the MRI scan | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fMRI, stress, peptide, social, neuroimaging