Pupil response to threat: A physiological marker for PTSD?
July 27, 2015
For a significant minority of the population, interpersonal violence leads to profoundly distressing symptoms of posttraumatic stress disorder (PTSD) and devastating functional impairment. Individual variability in response to violent trauma depends on a number of factors, including genetic susceptibility (Zoldaz & Diamond, 2013) and the potency of trauma exposure (Kessler et al., 1995). Being able to identify those who may be at risk for developing PTSD subsequent to trauma exposure has far reaching public health and clinical utility. Imagine the value of being able to identify individuals at risk for developing long lasting emotional scars after exposure to traumatic stress, and then using this information about susceptibility to prevent the onset of PTSD. This ability would not only improve the health related quality of life for at risk individuals (Lettinga et al., 2002), it would also decrease financial burden on the health-care system, enabling the US to accomplish national goals as outlined in newly enacted health-care reform policy (Patient Protection and Affordable Care Act of 2010). Other areas where this information would be valuable includes screening troops before deployment, first responders before working at the scene of an emergency, or children growing up in neighborhoods where exposure to community violence is a way of life. It is well established that a significant number of troops returning from tours of duty and first responders suffer PTSD. Furthermore, trauma exposure, PTSD and related impairments in academic achievement, physical health, and occupational attainment are prevalent among youth, and more so for those who reside in low income, urban centers (Fairbank, 2008). Thus, interrupting the development of PTSD, diminishing its severity, or shortening its course holds tremendous benefit to the individual and society.
The search for physiological markers for PTSD has been largely inconclusive to date (Zoldaz & Diamond, 2013); however, a less studied and promising marker for PTSD is pupil response. Pupillometry allows continuous measurements of involuntary physiological pupil reactions to visual stimuli (Granholm & Steinhauer, 2004). Yet, few reports have examined whether this reflex could serve as diagnostic marker of PTSD. Using eye-tracking technology, Cascardi, Armstrong, Chung, and Pare (in press) evaluated pupil responses to threatening and neutral pictures from the International Affective Picture System (Lang, Bradley, & Cuthbert, 2008). Pictures were matched on pre-identified characteristics, such as number and position of elements. Each picture was shown to participants for 30 seconds and presentation was balanced across participants so that an equal number of threat or neutral pictures appeared first. Threatening pictures depicted scenes of interpersonal violence. A sample of 40 trauma-exposed individuals who experienced at least one form of interpersonal violence, such as physical or sexual assault, were recruited for participation; 40% of participants met diagnostic criteria for PTSD using the Clinical Administered PTSD scale (Blake et al., 1995; Weathers, Keane, & Davidson, 2001).
This is the first study to show that individuals with PTSD exhibited significantly more pupil dilation to pictures with threatening content than trauma-exposed controls. This effect was observed independently of time-elapsed since trauma, cumulative violence exposure, and trait anxiety. It was also only detected in response to specific threat-relevant parts of the threatening pictures, such as a gun or a knife, and only for those with PTSD. Pupil response to neutral pictures was similar for both trauma-exposed groups. Pupil dilation may reflect increased activity of the sympathetic nervous system (Granholm & Steinhauer, 2004). Although the mechanism underlying the heightened physiological arousal in the PTSD group was not examined, existing research indicates that dysregulation of the brain networks that normally regulate fear is involved (Admon et al., 2009; Bremner, Elzinga, Schmahl, & Vermetten, 2008; Shin, Rauch, & Pitman, 2006).
The findings of this study suggest that pupil responses to threat constitute a potential physiological marker of PTSD. A major strength of this measure rests in its objectivity, improving detection of who may be at risk for PTSD and enhancing diagnostic precision. The public health and clinical value of this research is evident. In a matter of seconds, eye-tracking technology might be used to evaluate an individual’s risk for PTSD. An application like this has the potential to interrupt the development of PTSD in at risk individuals or confirm diagnosis. Additionally, for those already diagnosed with PTSD and undergoing psychological intervention, the absence of pupil dilation in response to threat could provide a physiological marker for positive therapeutic response. Future research would benefit from investigation of the utility of these applications to enhance diagnostic precision and risk assessment. Furthermore, future research would also benefit from prospective studies to determine whether pupil response to threat precedes or follows the onset of PTSD.
1) Which may be more likely: pupil response to threat in individuals with PTSD precedes the onset of trauma or reflects a physiological expression of arousal associated with the aftermath of trauma?
2) Can pupil dilation to threat be used during prolonged exposure sessions to gauge therapeutic response within and across treatment sessions?
3) What are the ethical concerns associated with research on pupil response to threat as a predictor of PTSD in children exposed to interpersonal trauma?
About the Authors
Michele Cascardi (blog author) is an Associate Professor in Child Advocacy and Policy at Montclair State University Robert D. McCormick Center for Child Advocacy, NJ and visiting faculty in the Center for Molecular and Behavioral Neuroscience, Rutgers- Newark, NJ. Her research focuses on trauma and dating violence, and pupil response as a physiological marker for PTSD.
Davine Armstrong is an MPH student at the Rutgers School of Public Health, and Research Laboratory Manager at the Center for Molecular and Behavioral Neuroscience at Rutgers-Newark, NJ. Her research focuses on improving health related quality of life through innovative techniques and health education interventions.
Leeyup Chung is a postdoctoral researcher in Department of Neurobiology at Duke University, NC. His research focuses on neural circuit for social interactions.
Admon, R., Lubin, G., Stern, O., Rosenberg, K., Sela, L., Ben-Ami, H., & Hendler, T.
(2009). Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity. Proceedings of the National Academy of Sciences, 106, 14120-14125.doi: 10.1073/pnas.0903183106
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman, F. D., Charney,
D. S., & Keane, T. M. (1995). The development of a clinician-administered PTSD scale. Journal of Traumatic Stress, 8, 75-90.
Bremner, J. D., Elzinga, B., Schmahl, C., & Vermetten, E. (2008). Structural and
functional plasticity of the human brain in posttraumatic stress disorder. Progressive Brain Research, 167, 171-186. doi:10.1016/S0079-6123(07)67012-5
Cascardi, M, Armstrong D, Chung, L & Pare, D. (in press). Pupil response to threat: A
comparison of trauma-exposed individuals with or without PTSD. Journal of Traumatic Stress.
Fairbank, J. A. (2008). The epidemiology of trauma and trauma related disorders in
children and youth. PTSD Research Quarterly, 19, 1, 1-8.
Granholm, E., & Steinhauer, S. R. (2004). Pupillometric measures of cognitive and
emotional processes. International Journal of Psychophysiology, 52, 1-6. doi:10.1016/j.ijpsycho.2003.12.001
Kessler, R. C., Berglund, P. A., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E.
(2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry, 62, 593-602. doi:10.1001/archpsyc.62.6.593.
Lettinga, K. D., Verbon, A., Nieuwkerk, P. T., Jonkers, R. E., Gersons, B. P. R., Prins, J. M., & Speelman, P. (2002). Health-related quality of life and posttraumatic stress disorder among survivors of an outbreak of Legionnaires Disease. Clinical Infectious Diseases, 35, 1-7.
Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (2008). International affective picture
system (IAPS): Affective ratings of pictures and instruction manual. Technical Report A-8. University of Florida, Gainesville, FL.
Patient Protection and Affordable Care Act, 42 U.S.C. § 18001 et seq. (2010).
Shin, L. M., Rauch, S. L., & Pitman, R. K. (2006). Amygdala, medial prefrontal cortex,
and hippocampal function in PTSD. Annals of New York Academy of Sciences, 1071, 67-79.
Weathers, F. W., Keane, T. M., & Davidson, J. R. (2001). Clinician-Administered PTSD
Scale: A review of the first ten years of research. Depression and Anxiety, 13, 132-156. doi: 10.1002/da.1029
Zoladz, P. R. & Diamond, D. M. (2013). Current status on behavioral and biological
markers of PTSD: A search for clarity in a conflicting literature. Neuroscience and Biobehavioral Reviews, 37, 860-895. doi.org/10.1016/j.neubiorev.2013.03.024