Impaired fear inhibition is a biomarker of PTSD but not depression
Open accessAbstract
BACKGROUND: A central problem in posttraumatic stress disorder (PTSD) is a reduced capacity to suppress fear under safe conditions. Previously, we have shown that combat-related PTSD patients have impaired inhibition of fear-potentiated startle (FPS). Given the high comorbidity between PTSD and depression, our goal was to see whether this impairment is specific to PTSD, or a non-specific symptom associated with both disorders. METHODS: Fear-potentiated startle was assessed in 106 trauma-exposed individuals divided into four groups: (a) No diagnosis control, (b) PTSD only, (c) major depression (MDD) only, and (d) comorbid PTSD and MDD. We used a novel conditional discrimination procedure, in which one set of shapes (the danger signal) was paired with aversive airblasts to the throat, and different shapes (the safety signal) were presented without airblasts. The paradigm also included fear inhibition transfer test. RESULTS: Subjects with comorbid MDD and PTSD had higher FPS to the safety signal and to the transfer test compared to controls and MDD only subjects. In contrast to the control and MDD groups, the PTSD and comorbid PTSD and MDD groups did not show fear inhibition to safety cues. CONCLUSIONS: These results suggest that impaired fear inhibition may be a specific biomarker of PTSD symptoms.
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PTSD has often been described as a disorder of impaired fear extinction.
“As PTSD has often been described as a disorder of impaired fear extinction (73, 185–187)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [185]
The Introduction describes reduced fear suppression under safe conditions as a core problem in PTSD. The Discussion also cites studies suggesting impaired fear suppression during extinction may be a risk factor. But this paper frames its own findings chiefly as impaired fear inhibition and safety-signal processing, rather than describing PTSD specifically as a disorder of impaired fear extinction. (LLM, conf=0.78)
Experimental — accuracy not yet measuredFear-potentiated startle can be dysregulated in PTSD.
“Studies in PTSD have shown that fear-potentiated startle can be dysregulated in PTSD (Jovanovic et al., 2010;Pole et al., 2003)”
From Physiological feelings (2019) · cites this paper as Jovanovic et al., 2010
Subjects with high hyperarousal symptoms show the greatest difficulty inhibiting a fear response to safety cues.
“For example, previous work has shown that subjects with high hyperarousal symptoms show the greatest difficulty inhibiting a fear response to safety cues (45).”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [45]
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Self-citationKroes, M. C. W., Dunsmoor, J. E., Hakimi, M., Oosterwaal, S., NYU PROSPEC collaboration, Meager, M. R., & Phelps, E. A. (2019) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsz039 · Cited by 46 · see citing works
Stevens, J. S., Ely, T. D., Sawamura, T., Guzman, D., Bradley, B., Ressler, K. J., & Jovanovic, T. (2016) · Depression and Anxiety · doi:10.1002/da.22506 · Cited by 40 · see citing works
Self-citationHarnett, N. G., Wood, K. H., Ference, E. W., Reid, M. A., Lahti, A. C., Knight, A. J., & Knight, D. C. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.04.010 · Cited by 31 · see citing works
Lieberman, L., Gorka, S. M., Funkhouser, C. J., Shankman, S. A., & Phan, K. L. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.04.002 · Cited by 30 · see citing works
Late glucocorticoid receptor antagonism changes the outcome of adult life stress
Ding, J., da Silva, M. S., Lingeman, J., Chen, X., Shi, Y., Han, F., & Meijer, O. C. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.05.014 · Cited by 26 · see citing works
Translational fear inhibition models as indices of trauma-related psychopathology
D. Norrholm, S., & Jovanovic, T. (2011) · Current Psychiatry Reviews · doi:10.2174/157340011797183193 · Cited by 17 · see citing works
- Authors
- Jovanovic, T., Norrholm, S. D., Blanding, N. Q., Davis, M., Duncan, E., Bradley, B., & Ressler, K. J.
- Affiliations
- Emory University (US)
- Howard Hughes Medical Institute (US)
- Venue
- Depression and Anxiety
- Publisher
- Hindawi Limited
- Published
- 2010-03
- Volume
- 27
- Issue
- 3
- Pages
- 244-251
- ISSN
- 1091-4269 (ISSN-L)
- 1520-6394
- PMC
- PMC2841213
- OpenAlex
- W2036863219
- Cited by
- 444
- References
- 42
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 16 · 2023: 23 · 2022: 30 · 2021: 37 · 2020: 32 · 2019: 32 · 2018: 32 · 2017: 25 · 2016: 45 · 2015: 33 · 2014: 39 · 2013: 33 · 2012: 25
- FWCI
- 28.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Depression and Anxiety (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Emory University
- National Institutes of Health (UL1TR000454)
- National Institute of Mental Health (MH 071537, R01MH071537, R56MH071537)
- National Center for Research Resources (M01-RR00039, M01RR000039)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- post-traumatic stress disorder, major depressive disorder, fear inhibition, fear-potentiated startle, conditional discrimination, safety signals, damage-associated molecular patterns, PTSD-depression comorbidity, war injuries, biomarkers
- MeSH terms
- Adolescent, Adult, Aged, Arousal, Depressive Disorder, Electromyography, Fear, Female, Humans, Inhibition, Psychological, Male, Middle Aged, Surveys and Questionnaires, Reflex, Startle, Stress Disorders, Post-Traumatic, Biomarkers, Comorbidity, Diagnostic and Statistical Manual of Mental Disorders, Young Adult
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