Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Prospective longitudinal assessment of sensorimotor gating as a risk/resiliency factor for posttraumatic stress disorder

Abstract

Little is understood about cognitive mechanisms that confer risk and resiliency for posttraumatic stress disorder (PTSD). Prepulse Inhibition (PPI) is a measure of pre-attentional response inhibition that is a stable cognitive trait disrupted in many neuropsychiatric disorders characterized by poor behavioral or cognitive inhibition, including PTSD. Differentiating between PTSD-related phenotypes that are pre-existing factors vs. those that emerge specifically after trauma is critical to understanding PTSD etiology and can only be addressed by prospective studies. This study tested the hypothesis that sensorimotor gating performance is associated with risk/resiliency for combat-related PTSD. As part of a prospective, longitudinal study, 1226 active duty Marines and Navy Corpsman completed a PPI test as well as a clinical interview to assess PTSD symptoms both before,  and 3 and 6 months after a combat deployment. Participants that developed PTSD 6 months following deployment (N=46)  showed lower PPI across pre and post-deployment time points compared to participants who did not develop PTSD (N=1182) . Examination of the distribution of PTSD across PPI performance revealed a lower than expected number of cases in the highest performing quartile compared to the rest of the distribution (p < 0.04). When controlling for other factors that predict PTSD in this population, those in the top 25% of PPI performance showed a >50% reduction in chance to develop PTSD (OR = 0.32). Baseline startle reactivity and startle habituation were not significantly different between PTSD risk and control groups. These findings suggest that robust sensorimotor gating may represent a resiliency factor for development of PTSD following trauma.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: PPI performance before and after deployment in those that did and did not go on to develop PTSD post-deployment.
Fig. 2: Startle reactivity and habituation do not differ across those that did and did not go on to develop PTSD post deployment.
Fig. 3: Prevalence of PTSD in top PPI performers.

References

  1. Druss BG, Hwang I, Petukhova M, Sampson NA, Wang PS, Kessler RC. Impairment in role functioning in mental and chronic medical disorders in the United States: results from the National Comorbidity Survey Replication. Mol Psychiatry. 2008;14:728–37.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, et al. Disability and quality of life impact of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl. 2004;109:21–27.

    Article  Google Scholar 

  3. Breslau N. The epidemiology of trauma, PTSD, and other posttrauma disorders. Trauma Violence Abuse. 2009;10:198–210.

    Article  PubMed  Google Scholar 

  4. Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress. 2013;26:537–47.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Zhang L, Li H, Benedek D, Li X, Ursano R. A strategy for the development of biomarker tests for PTSD. Med Hypotheses. 2009;73:404–9.

    Article  PubMed  Google Scholar 

  6. Swerdlow NR, Braff DL, Geyer MA. Cross-species studies of sensorimotor gating of the startle reflex. Ann N Y Acad Sci. 1999;877:202–16.

    Article  CAS  PubMed  Google Scholar 

  7. Greenwood TA, Braff DL, Light GA, Cadenhead KS, Calkins ME, Dobie DJ, et al. Initial heritability analyses of endophenotypic measures for Schizophrenia: the consortium on the genetics of schizophrenia. Arch Gen Psychiatry. 2007;64:1242–50.

    Article  PubMed  Google Scholar 

  8. Kohl S, Heekeren K, Klosterkötter J, Kuhn J. Prepulse inhibition in psychiatric disorders - apart from schizophrenia. J Psychiatr Res. 2013;47:445–52.

    Article  CAS  PubMed  Google Scholar 

  9. Flaten MA. Test-retest reliability of the somatosensory blink reflex and its inhibition. Int J Psychophysiol. 2002;45:261–5.

    Article  PubMed  Google Scholar 

  10. Abel K, Waikar M, Pedro B, Hemsley D, Geyer M. Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls. J Psychopharmacol. 1998;12:330–7. 337

    Article  CAS  PubMed  Google Scholar 

  11. Schwarzkopf SB, McCoy L, Smith DA, Boutros NN. Test-retest reliability of prepulse inhibition of the acoustic startle response. Biol Psychiatry. 1993;34:896–900.

    Article  CAS  PubMed  Google Scholar 

  12. Ludewig K, Ludewig S, Seitz A, Obrist M, Geyer MA, Vollenweider FX. The acoustic startle reflex and its modulation: effects of age and gender in humans. Biol Psychol. 2003;63:311–23.

    Article  PubMed  Google Scholar 

  13. Francis DD, Szegda K, Campbell G, Martin WD, Insel TR. Epigenetic sources of behavioral differences in mice. Nat Neurosci. 2013;6:445–6.

    Article  Google Scholar 

  14. Swerdlow NR, Light GA, Cadenhead KS, Sprock J, Hsieh MH, Braff DL. Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function. Arch Gen Psychiatry. 2006;63:1325–35.

    Article  PubMed  Google Scholar 

  15. Castellanos FX, Fine EJ, Kaysen D, Marsh WL, Rapoport JL, Hallett M. Sensorimotor gating in boys with Tourette’s syndrome and ADHD: preliminary results. Biol Psychiatry. 1996;39:33–41.

    Article  CAS  PubMed  Google Scholar 

  16. Perry W, Minassian A, Feifel D, Braff DL. Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania. Biol Psychiatry. 2001;50:418–24.

    Article  CAS  PubMed  Google Scholar 

  17. Ahmari SE, Risbrough VB, Geyer MA, Simpson HB. Impaired sensorimotor gating in unmedicated adults with obsessive-compulsive disorder. Neuropsychopharmacology. 2012;37:1216–23.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ludewig S, Ludewig K, Geyer MA, Hell D, Vollenweider FX. Prepulse inhibition deficits in patients with panic disorder. Depress Anxiety. 2002;15:55–60.

    Article  CAS  PubMed  Google Scholar 

  19. Nievergelt CM, Maihofer AX, Klengel T, Atkinson EG, Chen CY, Choi KW, et al. International meta-analysis of PTSD genome-wide association studies identifies sex and ancestry-specific genetic risk loci. Nat Commun. 2019;10:4558.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Stein MB, Levey DF, Cheng Z, Wendt FR, Harrington K, Pathak GA, et al. Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program. Nat Genet. 2021;53:174–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Risbrough VB, Vaughn MN, Friend SF. Role of inflammation in traumatic brain injury–associated risk for neuropsychiatric disorders: state of the evidence and where do we go from here. Biol Psychiatry. 2022;91:438–48.

    Article  CAS  PubMed  Google Scholar 

  22. Swerdlow NR, Braff DL, Geyer MA. Sensorimotor gating of the startle reflex: What we said 25 years ago, what has happened since then, and what comes next. Psychopharmacology. 2016;30:1072–81.

    Article  Google Scholar 

  23. Swerdlow NR, Geyer MA, Braff DL. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology. 2001;156:194–215.

    Article  CAS  PubMed  Google Scholar 

  24. Naysmith LF, Kumari V, Williams SCR. Neural mapping of prepulse-induced startle reflex modulations as indices of sensory information processing in healthy and clinical populations: a systematic review. Hum Brain Mapp. 2021;42:5495–518.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Braff DL, Geyer MA, Swerdlow NR. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology. 2001;156:234–58.

    Article  CAS  PubMed  Google Scholar 

  26. Acheson DT, Gresack JE, Risbrough VB. Hippocampal dysfunction effects on context memory: Possible etiology for posttraumatic stress disorder. Neuropharmacology. 2012;62:674–85.

    Article  CAS  PubMed  Google Scholar 

  27. Ressler KJ, Berretta S, Bolshakov VY, Rosso IM, Meloni EG, Rauch SL, et al. Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits. Nat Rev Neurol. 2022;18:273–88.

    Article  CAS  PubMed  Google Scholar 

  28. Ornitz EM, Pynoos RS. Startle modulation in children with posttraumatic stress disorder. Am J Psychiatry. 1989;146:866–70.

    Article  CAS  PubMed  Google Scholar 

  29. Grillon C, Morgan CA, Southwick SM, Davis M, Charney DS. Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder. Psychiatry Res. 1996;64:169–78.

    Article  CAS  PubMed  Google Scholar 

  30. Grillon C, Morgan CA 3rd, Davis M, Southwick SM. Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder. Biol Psychiatry. 1998;44:1027–36.

    Article  CAS  PubMed  Google Scholar 

  31. Echiverri-Cohen AM, Zoellner LA, Ho W, Husain J. An analysis of inhibitory functioning in individuals with chronic posttraumatic stress disorder. J Anxiety Disord. 2016;37:94–103.

    Article  PubMed  Google Scholar 

  32. Pineles SL, Blumenthal TD, Curreri AJ, Nillni YI, Putnam KM, Resick PA, et al. Prepulse inhibition deficits in women with PTSD. Psychophysiology. 2016;53:1377–85.

    Article  PubMed  Google Scholar 

  33. Butler RW, Braff DL, Rausch JL, Jenkins MA, Sprock J, Geyer MA. Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat-related PTSD. Am J Psychiatry. 1990;147:1308–12.

    Article  CAS  PubMed  Google Scholar 

  34. Lipschitz DS, Mayes LM, Rasmusson AM, Anyan W, Billingslea E, Gueorguieva R, et al. Baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder. J Am Acad Child Adolesc Psychiatry. 2005;44:807–14.

    Article  PubMed  Google Scholar 

  35. Holstein DH, Vollenweider FX, Jancke L, Schopper C, Csomor PA. P50 suppression, prepulse inhibition, and startle reactivity in the same patient cohort suffering from posttraumatic stress disorder. J Affect Disord. 2010;126:188–97.

    Article  PubMed  Google Scholar 

  36. Vrana SR, Calhoun PS, McClernon FJ, Dennis MF, Lee ST, Beckham JC. Effects of smoking on the acoustic startle response and prepulse inhibition in smokers with and without posttraumatic stress disorder. Psychopharmacology. 2013;230:477–85.

    Article  CAS  PubMed  Google Scholar 

  37. Meteran H, Vindbjerg E, Wiingaard Uldall S, Glenthoj B, Carlsson J, Orange B. Startle habituation, senory, and sensorimotor gating in trauma-affected refuges with posttraumatic stress disorder. Psychol Med. 2018;49:581–9.

    Article  PubMed  Google Scholar 

  38. Bakshi VP, Alsene KM, Roseboom PH, Connors EE. Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits? Neuropharmacology. 2012;62:737–48.

    Article  CAS  PubMed  Google Scholar 

  39. Risbrough VB, Hauger RL, Roberts AL, Vale WW, Geyer MA. Corticotropin-releasing factor receptors CRF1 and CRF2 exert both additive and opposing influences on defensive startle behavior. J Neurosci. 2004;24:6545–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Flandreau E, Risbrough V, Lu A, Ableitner M, Geyer MA, Holsboer F, et al. Cell type-specific modifications of corticotropin-releasing factor (CRF) and its type 1 receptor (CRF) on startle behavior and sensorimotor gating. Psychoneuroendocrinology. 2014;53C:16–28.

    Google Scholar 

  41. Rajbhandari AK, Baldo BA, Bakshi VP. Predator stress-induced CRF release causes enduring sensitization of basolateral amygdala norepinephrine systems that promote PTSD-like startle abnormalities. J Neurosci. 2015;35:14270–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Baker DG, Nash WP, Litz BT, Geyer MA, Risbrough VB, Nievergelt CM, et al. Predictors of risk and resilience for posttraumatic stress disorder among ground combat Marines: methods of the Marine Resiliency Study. Prev Chronic Dis. 2012;9:E97.

    PubMed  PubMed Central  Google Scholar 

  43. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, et al. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995;8:75–90.

    Article  CAS  PubMed  Google Scholar 

  44. Blanchard EB, Hickling EJ, Taylor AE, Forneris CA, Loos W, Jaccard J. Effects of varying scoring rules of the Clinician-Administered PTSD Scale (CAPS) for the diagnosis of post-traumatic stress disorder in motor vehicle accident victims. Behav Res Ther. 1995;33:471–5.

    Article  CAS  PubMed  Google Scholar 

  45. Blanchard EB, Hickling EJ, Taylor AE, Loos W. Psychiatric morbidity associated with motor vehicle accidents. J Nerv Ment Dis. 1995;183:495–504.

    Article  CAS  PubMed  Google Scholar 

  46. Blanchard EB, Hickling EJ, Buckley TC, Taylor AE, Vollmer A, Loos WR. Psychophysiology of posttraumatic stress disorder related to motor vehicle accidents: replication and extension. J Consult Clin Psychol. 1996;64:742–51.

    Article  CAS  PubMed  Google Scholar 

  47. Weathers FW, Ruscio AM, Keane TM. Psychometric properties of nine scoring rules for the Clinician-Administered Post-traumatic Stress Disorder Scale. Psychological Assess. 1999;11:124–33.

    Article  Google Scholar 

  48. King LA, King DW, Vogt DS, Knight J, Samper RE. Deployment Risk and Resilience Inventory: a collection of measures for studying deployment-related experiences of military personnel and veterans. Mil Psychol. 2006;18:89–120.

    Article  Google Scholar 

  49. Nievergelt CM, Maihofer AX, Shekhtman T, Libiger O, Wang X, Kidd KK, et al. Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel. Investig Genet. 2013;4:13.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Yurgil KA, Barkauskas DA, Vasterling JJ, Nievergelt CM, Larson GE, Schork NJ, et al. Association between traumatic brain injury and risk of posttraumatic stress disorder in active-duty Marines. JAMA Psychiatry. 2014;71:149–57.

    Article  PubMed  Google Scholar 

  51. von Holst H, Cassidy JD. Mandate of the WHO Collaborating Centre Task Force on mild traumatic brain injury. J Rehabil Med. 2004:43;8–10.

  52. Gray MJ, Litz BT, Hsu JL, Lombardo TW. Psychometric properties of the life events checklist. Assessment. 2004;11:330–41.

    Article  PubMed  Google Scholar 

  53. Braff DL, Grillon C, Geyer MA. Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry. 1992;49:206–15.

    Article  CAS  PubMed  Google Scholar 

  54. Acheson DT, Stein MB, Paulus MP, Geyer MA, Risbrough VB. The effect of pregabalin on sensorimotor gating in ‘low’ gating humans and mice. Neuropharmacology. 2012;63:480–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Glenn DE, Acheson DT, Geyer MA, Nievergelt CM, Baker DG, Risbrough VB. High and low threshold for startle reactivity associated with Ptsd symptoms but not Ptsd risk: evidence from a prospective study of active duty marines. Depress Anxiety. 2016;33:192–202.

    Article  PubMed  Google Scholar 

  56. Acheson DT, Stein MB, Paulus MP, Ravindran L, Simmons AN, Lohr JB, et al. Effects of anxiolytic treatment on potentiated startle during aversive image anticipation. Hum Psychopharmacol Clin Exp. 2012;27:419–27.

    Article  CAS  Google Scholar 

  57. Swerdlow NR, Sprock J, Light GA, Cadenhead K, Calkins ME, Dobie DJ, et al. Multi-site studies of acoustic startle and prepulse inhibition in humans: initial experience and methodological considerations based on studies by the Consortium on the Genetics of Schizophrenia. Schizophr Res. 2007;92:237–51.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Swerdlow NR, Light GA, Sprock J, Calkins ME, Green MF, Greenwood TA, et al. Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS. Schizophr Res. 2014;152:503–12.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Acheson DT, Geyer MA, Risbrough VB. Psychophysiology in the study of psychological trauma: where are we now and where do we need to be? Curr Top Behav Neurosci. 2014;21:157–83.

    Article  CAS  PubMed  Google Scholar 

  60. Admon R, Milad MR, Hendler T. A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities. Trends Cogn Sci. 2013;17:337–47.

    Article  PubMed  Google Scholar 

  61. Kumari V, Antonova E, Zachariah E, Galea A, Aasen I, Ettinger U, et al. Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans. Neuroimage. 2005;26:1052–8.

    Article  PubMed  Google Scholar 

  62. Hazlett EA, Buchsbaum MS, Haznedar MM, Singer MB, Germans MK, Schnur DB, et al. Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients. Psychophysiology. 1998;35:186–98.

    Article  CAS  PubMed  Google Scholar 

  63. Neuner I, Stöcker T, Kellermann T, Ermer V, Wegener HP, Eickhoff SB, et al. Electrophysiology meets fMRI: neural correlates of the startle reflex assessed by simultaneous EMG-fMRI data acquisition. Hum Brain Mapp. 2010;31:1675–85.

    PubMed  PubMed Central  Google Scholar 

  64. Kumari V, Fannon D, Geyer MA, Premkumar P, Antonova E, Simmons A, et al. Cortical grey matter volume and sensorimotor gating in schizophrenia. Cortex. 2008;44:1206–14.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ota M, Sato N, Matsuo J, Kinoshita Y, Kawamoto Y, Hori H, et al. Multimodal image analysis of sensorimotor gating in healthy women. Brain Res. 2013;1499:61–68.

    Article  CAS  PubMed  Google Scholar 

  66. Swerdlow NR, Light GA. Neurophysiological biomarkers informing the clinical neuroscience of schizophrenia: mismatch negativity and prepulse inhibition of startle. Curr Topics Behav Neurosci. 2022, in press..

  67. Light GA, Swerdlow NR, Rissling AJ, Radant A, Sugar CA, Sprock J, et al. Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia. PLoS ONE. 2012;7:e39434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Greenwood TA, Light GA, Swerdlow NR, Calkins ME, Green MF, Gur RE, et al. Gating deficit heritability and correlation with increased clinical severity in schizophrenia patients with positive family history. Am J Psychiatry. 2016;173:385–91.

    Article  PubMed  Google Scholar 

  69. Quednow BB, Ejebe K, Wagner M. Meta-analysis on the association between genetic polymorphisms and prepulse inhibition of the acoustic startle response. Schizophr Res. 2018;198:52–59.

    Article  PubMed  Google Scholar 

  70. Vinogradov S, Fisher M, de Villers-Sidani E. Cognitive training for impaired neural systems in neuropsychiatric illness. Neuropsychopharmacology. 2012;37:43–76.

    Article  PubMed  Google Scholar 

Download references

Funding

Support for this work includes NIMH P50MH096889 (DGB and VBR), a Department of Veterans Affairs Merit Award and NIH R01AA026560 (VBR), project No. SDR 09-0128 (DGB and VBR) from the Veterans Administration Health Service Research and Development, the US Marine Corps and Navy Bureau of Medicine and Surgery (DGB and VBR), and the Center of Excellence for Stress and Mental Health (all authors). VBR is also the recipient of a Research Career Scientist award (# IK6BX006186) from the Department of Veterans Affairs.  The project described was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR001414. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Authors and Affiliations

Authors

Contributions

VBR, MAG, and DGB designed the study and supervised data collection and edited the manuscript, DTA contributed to data collection, conducted the analysis, and lead the manuscript preparation, CMN, KAY, and VBR aided data collection, processing, and analysis and edited the manuscript.

Corresponding author

Correspondence to Victoria B. Risbrough.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Acheson, D.T., Baker, D.G., Nievergelt, C.M. et al. Prospective longitudinal assessment of sensorimotor gating as a risk/resiliency factor for posttraumatic stress disorder. Neuropsychopharmacol. 47, 2238–2244 (2022). https://doi.org/10.1038/s41386-022-01460-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41386-022-01460-9

Search

Quick links