Fear-potentiated startle in posttraumatic stress disorder

doi:10.1016/0006-3223(94)00321-S

Biological Psychiatry

Volume 38, Issue 6, 15 September 1995, Pages 378-385

https://doi.org/10.1016/0006-3223(94)00321-S Get rights and content

Exaggerated startle is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD); however, objective studies have given conflicting results as to whether or not startle is increased in PTSD. The present study investigated startle in PTSD during the threat of shock (fear-potentiated startle). The eyeblink component of the startle reflex was measured at various times preceding and following the anticipation of unpleasant electric shocks in 9 PTSD subjects and 10 age-matched, healthy controls. Startle amplitude was significantly greater during baseline and during shock anticipation in the PTSD subjects, compared to the controls. Habituation of the startle reflex was normal. Because other studies in the literature, as well as in our own laboratory, have failed to find exaggerated startle at baseline (i.e., absence of stress) in PTSD patients, it is unlikely that the present results reflect a chronic elevation of startle in this group. Instead, the higher levels of startle in the PTSD group probably resulted from a greater conditioned emotional response in this group, triggered by anticipation of electric shocks that generalized to the unfamiliar experimental context in which testing occurred. Hence, emotionally charged test procedures may be especially informative in distinguishing PTSD patients from other psychiatric diagnostic groups.

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Fear-potentiated startle (FPS) has been widely used to study fear processing in humans and rodents. Human studies showed higher startle amplitudes and exaggerated fear reactivity to unpredictable vs. predictable threats in individuals suffering from post-traumatic stress disorder (PTSD). Although human FPS studies use both sexes, a surprisingly limited number of rodent FPS studies use females. Here we investigate the effects of signal-threat contingency, signal-threat order and threat predictability on FPS in both sexes. We use a classic fear-conditioning protocol (100% contingency of cue and shock pairings, with forward conditioning such that the cue co-terminates with the shock) and compare it to modified fear-conditioning protocols (70% contingency; backward conditioning; or cue and shock un-paired). Although there are no sex differences in the startle amplitudes when corrected for body weight, females consistently demonstrate higher shock reactivity during fear-conditioning. Both sexes and strains demonstrate comparable levels of cued, non-cued, and contextual fear in the classic FPS and FPS following fear-conditioning with 70% contingency or backward order (cue co-starts with shock). However, in the classic FPS, Sprague-Dawley females show reduced proportion between cued fear and cue-elicited vigilant state than males. Lastly, a prominent sex difference is uncovered following unpredictable fear-conditioning (cue and shock un-paired), with Wistar, but not Sprague-Dawley, females showing significantly higher startle overall during the FPS recall, regardless of trial type, and higher contextual fear than males. This striking sex difference in processing unpredictable threats in rodent FPS might help to understand the mechanisms underlying higher incidence of PTSD in women.
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This study develops a fear-potentiated startle paradigm (FPS) and a machine learning approach to accurately predict PTSD symptoms using electrogram data. A three-phase fear-potentiated startle paradigm was designed to assess the conditioning, generalization, and extinction of fear. Electrooculogram and electrocardiogram signals were collected during the FPS. A total of 1107 Chinese firefighters participated in the study. The Chinese version PCL-C was administered to all subjects. A cutoff of 38 or higher is used to indicate PTSD symptoms. Electrogram features were extracted and selected to build a machine learning model to classify individuals. The machine learning model was 5-fold cross validated. The importance of the selected features was calculated. Classification performance metrics were evaluated for the machine learning model. The machine learning model can identify firefighters with a PCL-C score of 38 or above with sensitivity and specificity both above 0.85 when 5-fold cross validated on a 1107-person sample. The area under the receiver operating characteristic curve of the model is 0.93. Features related to fear generalization are found to be the most important. The proposed fear-potentiated startle paradigm and machine learning approach can accurately predict PTSD symptoms in Chinese firefighters, which can improve the screening and diagnosis of PTSD.
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: This work was supported by the National Center for Posttraumatic Stress Disorder, NIMH grants 1R29MH50720 (CG) and RO1-MH40140 (DSC), and MH47840, Research Scientist Development Award MH-00004, and a grant from the Air Force Office of Scientific Research (MD).

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Original articleFear-potentiated startle in posttraumatic stress disorder

Offline latency and amplitude scoring of the human reflex eyeblink with Fortran IV (computer program abstract)

Psychophysiology

Cardiac response to relevant stimuli as an adjunctive tool for diagnosis of posttraumatic stress disorder in Vietnam veterans

Behav Ther

A psychophysiological study of posttraumatic stress disorder in Vietnam veterans

Psychiatr Q

Conditioned fear as revealed by magnitude of startle response to an auditory stimulus

J Exp Psychol

Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat related PTSD

Am J Psychiatry

Diazepam and flurazepam: Effects on conditioned fear as measured by the potentiated startle paradigm

Psychopharmacology

The role of the amygdala in fear and anxiety

Ann Rev Neurosci

Conditioned fear and startle magnitude: Effects of different footshock or backshock intensities

J Exp Psychol

Noradrenergic agonists and antagonists: Effects on conditioned fear as measured by the potentiated startle paradigm

Psychopharmacology

Assessment of sympathetic nervous function in humans from noradrenaline kinetics

Clin Sci

Fear potentiated startle in humans

Effects of anticipatory anxiety on the acoustic blink reflex

Psychophysiology

Measuring the time-course of anxiety using the fear-potentiated startle reflex

Psychophysiology

Baseline and fear-potentiated startle in panic disorder patients

Biol Psychiatry

Men Under Stress

Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm

Behav Neurosci

Efferent pathway of the amygdala involved in conditioned fear as measured with the fear-potentiated startle paradigm

Behav Neurosci

The Traumatic Neurosis of War

Original article
Fear-potentiated startle in posttraumatic stress disorder