Toward an Objective Assessment of Fight-or-Flight System Function in Anxiety Disorders: Startle Reflex Modulation in Threat Coping Contexts as a Candidate Neurophysiological Marker of Disrupted Defense System Operation
- 1Medical University of South Carolina
Abstract
Background: As a key mechanism of disorder, clinical anxiety changes how a defensive motivation system functions in active threat coping contexts. Building on initial evidence that a lab-based escape/avoid preparation task is sensitive to disruptions in underlying defensive activation, current research moved toward implementation as a clinical assessment by testing if task responding predicts symptoms in anxiety treatment seekers. Methods: In our escape/avoid task, unpleasant images are shown after 5.5-second cues that indicate if the upcoming image can be prevented (avoid context), terminated after onset (escape context), or not controlled (no-control comparator). To assess defensive activation during response preparation/threat anticipation, a startle reflex indicator of such activation is probed during each cue. Guided by prior data, 125 individuals were classified into groups based on whether startle was enhanced 1) in a no-control, relative to avoid, context, and 2) in an escape, relative to avoid, context. To test clinical correlates, anxiety (State-Trait Anxiety Inventory), depression (Beck Depression Inventory), and worry (Penn State Worry Questionnaire) were then compared across response groups. Results: Anxiety and worry were higher in participants with enhanced no-control and escape startle than in participants with enhanced no-control but not escape startle. Further, depression was higher in participants with under-enhancement of no-control startle than other groups. Finally, when comparing startle-based profiles to canonical questionnaire cut-off score-based groups, ~54-63% convergence emerged. Conclusions: Defensive profiling in escape/avoid contexts shows promise as a prognostic indicator, but a need to continue improving is also indicated. Possibilities to improve predictiveness and reliability are discussed.
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BibTeX
@misc{gertler2026toward,
title = {{Toward an Objective Assessment of Fight-or-Flight System Function in Anxiety Disorders: Startle Reflex Modulation in Threat Coping Contexts as a Candidate Neurophysiological Marker of Disrupted Defense System Operation}},
author = {J. H. Gertler and C. Marsicano and M. S. George and L. M. McTeague and C. T. Sege},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.751525},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.751525v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Toward an Objective Assessment of Fight-or-Flight System Function in Anxiety Disorders: Startle Reflex Modulation in Threat Coping Contexts as a Candidate Neurophysiological Marker of Disrupted Defense System Operation
AU - J. H. Gertler
AU - C. Marsicano
AU - M. S. George
AU - L. M. McTeague
AU - C. T. Sege
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.751525
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.751525v1
AB - Background: As a key mechanism of disorder, clinical anxiety changes how a defensive motivation system functions in active threat coping contexts. Building on initial evidence that a lab-based escape/avoid preparation task is sensitive to disruptions in underlying defensive activation, current research moved toward implementation as a clinical assessment by testing if task responding predicts symptoms in anxiety treatment seekers. Methods: In our escape/avoid task, unpleasant images are shown after 5.5-second cues that indicate if the upcoming image can be prevented (avoid context), terminated after onset (escape context), or not controlled (no-control comparator). To assess defensive activation during response preparation/threat anticipation, a startle reflex indicator of such activation is probed during each cue. Guided by prior data, 125 individuals were classified into groups based on whether startle was enhanced 1) in a no-control, relative to avoid, context, and 2) in an escape, relative to avoid, context. To test clinical correlates, anxiety (State-Trait Anxiety Inventory), depression (Beck Depression Inventory), and worry (Penn State Worry Questionnaire) were then compared across response groups. Results: Anxiety and worry were higher in participants with enhanced no-control and escape startle than in participants with enhanced no-control but not escape startle. Further, depression was higher in participants with under-enhancement of no-control startle than other groups. Finally, when comparing startle-based profiles to canonical questionnaire cut-off score-based groups, ~54-63% convergence emerged. Conclusions: Defensive profiling in escape/avoid contexts shows promise as a prognostic indicator, but a need to continue improving is also indicated. Possibilities to improve predictiveness and reliability are discussed.
ER -