Posttraumatic stress disorder (PTSD) affects a significant proportion of the population, with general population estimates ranging from 6.4% to 6.8%. To-date there is no biological markers to identify individuals at risk for PTSD, and available treatments are only partially successful. Understanding the behavioral and neural mechanisms that underlie the development and maintenance of PTSD is important in order to inform and refine behavioral and pharmacotherapeutic interventions designed to improve patients'quality of life and, ideally, to prevent the disorder in the first place. One aspect of mst traumas that is widely ignored in the context of PTSD is the high levels of uncertainty surrounding highly adverse circumstances. In the battlefield, for example, soldiers are aware of the various dangers to themselves and others, but are seldom able to estimate the likelihood for the realization of those dangers. An adverse outcome combined with the distress of uncertainty is likely to be associated with more deleterious outcomes (e.g., greater severity of PTSD symptoms) than the same outcome in the absence of such distress. The individual's ability to cope with uncertainty may therefore determine their reaction to extreme harmful events, as well as their ability to psychologically adapt to such events. At the same time, the association of uncertainty with harmful outcomes may subsequently augment the individual's aversion for uncertainty. Behavioral economics analysis suggests that behavior under uncertainty is affected by the individual's weighting of two separate factors: (1) risk attitude, which reflects a trade-of between the probabilities of gains or losses, and the magnitude of those gains and losses~ and (2) ambiguity attitude, which reflects an individual's sensitivity to missing information about these probabilities. Neuroeconomics studies show that risk and ambiguity attitudes are reflected in the neural activation in regions of the medial prefrontal cortex (MPFC), the striatum and the amygdala, all areas that have been implicated in valuation processes in general. Intriguingly, these very same areas show structural and functional abnormalities in PTSD. In this proposal, we aim to characterize behavior under uncertainty and its neural correlates in trauma survivors with and without PTSD and healthy controls with no trauma experience. We hypothesize that individuals with PTSD will be more averse to ambiguity, and that trauma controls will be less averse to ambiguity compared to non-trauma-exposed controls. We further hypothesize that in individuals with PTSD activity in valuation areas, which normally reflects attitudes towards risk and ambiguity will cease to do so under conditions of ambiguous losses. We plan to test these hypotheses using a combination of functional MRI and experimental economics behavioral methods.

Public Health Relevance

Our attitudes towards uncertainty shape nearly every aspect of our behavior, including our reactions to extreme adverse outcomes whose occurrence is uncertain, such as being in an accident or the death of a loved one. Is intolerance to uncertainty associated with PTSD? We propose an analysis of the precise behavioral and neural basis of uncertainty attitudes in trauma survivors with and without PTSD and healthy controls with no trauma experience to better understand the neural basis of PTSD. Such understanding will inform and refine behavioral and pharmacotherapeutic interventions designed to improve patients'quality of life and, ideally, to prevent the disorder in the first place.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH102634-01A1
Application #
8709712
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Borja, Susan
Project Start
2014-03-17
Project End
2016-02-28
Budget Start
2014-03-17
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$249,750
Indirect Cost
$99,750
Name
Yale University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520