Psychophysiological Markers of Fear and Anxiety

  • Jamiah Hyde
  • Katherine M. Ryan
  • Allison M. WatersEmail author
Anxiety Disorders (A Pelissolo, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Anxiety Disorders


Purpose of Review

The purpose of this paper is to provide a current review of the recent literature (2015–2018) on psychophysiological markers of fear and anxiety.

Recent Finding

Relative to healthy controls, fear-based disorders are characterised by heightened physiological reactivity to circumscribe threat salient stimuli, whereas anxiety-related disorders are associated with a more blunted pattern of physiological reactivity.


Fear and anxiety disorders are marked by abnormal patterns of physiological reactivity, characterised by hyper- and hypo-reactivity in response to stimuli varying in threat salience.


Fear Anxiety Psychophysiology Markers 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Slade T, Johnston A, Oakley Browne MA, Andrews G, Whiteford H. 2007 national survey of mental health and wellbeing: methods and key findings. Aust N Z J Psychiatry. 2009;43(7):594–605.CrossRefGoogle Scholar
  2. 2.
    Lawrence D, Johnson S, Hafekost J, Boterhoven de Hann K, Sawyer M, Ainley J et al. The mental health of children and adolescents. Report on the second Australian child and adolescent survey of mental health and wellbeing. Department of Health, Canberra; 2015.Google Scholar
  3. 3.
    Berntson GG, Cacioppo JT, Quigley KS. Autonomic determinism: the modes of autonomic control, the doctrine of autonomic space, and the laws of autonomic constraint. Psychol Rev. 1991;98(4):459–87.CrossRefGoogle Scholar
  4. 4.
    Norman GJ, Cacioppo JT, Morris JS, Malarkey WB, Berntson GG, DeVries AC. Oxytocin increases autonomic cardiac control: moderation by loneliness. Biol Psychol. 2011;86(3):174–80.CrossRefGoogle Scholar
  5. 5.
    Porges SW. The Norton series on interpersonal neurobiology. The polyvagal theory: Neurophysiological foundations of emotions, attachment, communication, and self-regulation. New York, NY, US: W W Norton & Co 2011.Google Scholar
  6. 6.
    Frewen PA, Dozois DJ, Lanius RA. Neuroimaging studies of psychological interventions for mood and anxiety disorders: empirical and methodological review. Focus. 2010;8(1):92–109.CrossRefGoogle Scholar
  7. 7.
    Marwood L, Wise T, Perkins AM, Cleare AJ. Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety. Neurosci Biobehav Rev. 2018;95:61–72.CrossRefGoogle Scholar
  8. 8.
    Dawson ME, Schell AM, Courtney CG. The skin conductance response, anticipation, and decision-making. J Neurosci Psychol Econ. 2011;4(2):111–6. Scholar
  9. 9.
    Grillon C. Associative learning deficits increase symptoms of anxiety in humans. Biol Psychiatry. 2002;51(11):851–8. Scholar
  10. 10.
    Henderson RR, Bradley MM, Lang PJ. Emotional imagery and pupil diameter. Psychophysiology. 2018;55(6):e13050-n/a. Scholar
  11. 11.
    Bradley MM, Miccoli L, Escrig MA, Lang PJ. The pupil as a measure of emotional arousal and autonomic activation. Psychophysiology. 2008;45(4):602–7. Scholar
  12. 12.
    Nater UM, Rohleder N. Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology. 2009;34(4):486–96.CrossRefGoogle Scholar
  13. 13.
    Schumacher S, Kirschbaum C, Fydrich T, Ströhle A. Is salivary alpha-amylase an indicator of autonomic nervous system dysregulations in mental disorders?—a review of preliminary findings and the interactions with cortisol. Psychoneuroendocrinology. 2013;38(6):729–43.CrossRefGoogle Scholar
  14. 14.
    Kemp AH, Koenig J, Thayer JF. From psychological moments to mortality: a multidisciplinary synthesis on heart rate variability spanning the continuum of time. Neurosci Biobehav Rev. 2017;83:547–67.CrossRefGoogle Scholar
  15. 15.
    Mather M, Thayer JF. How heart rate variability affects emotion regulation brain networks. Curr Opin Behav Sci. 2018;19:98–104. Scholar
  16. 16.
    Thayer JF, Åhs F, Fredrikson M, Sollers JJ, Wager TD, Institutionen för p, et al. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev. 2012;36(2):747–56. Scholar
  17. 17.
    •• Kotov R, Krueger RF, Watson D, Achenbach TM, Althoff RR, Bagby RM, et al. The hierarchical taxonomy of psychopathology (HiTOP): a dimensional alternative to traditional nosologies. J Abnorm Psychol. 2017;126(4):454–77. This paper outlines an innovative new model of psychopathology, the Hierarchical Taxonomy of Psychopathology (HiTOP), which organises psychopathological syndromes using dimensional criteria. CrossRefGoogle Scholar
  18. 18.
    Clark LA, Watson D. Distress and fear disorders: an alternative empirically based taxonomy of the ‘mood’ and ‘anxiety’disorders. Br J Psychiatry. 2006;189(6):481–3.CrossRefGoogle Scholar
  19. 19.
    Waters AM, Pine DS. Evaluating differences in Pavlovian fear acquisition and extinction as predictors of outcome from cognitive behavioural therapy for anxious children. J Child Psychol Psychiatry. 2016;57(7):869–76.CrossRefGoogle Scholar
  20. 20.
    •• Waters AM, Craske MG. Towards a cognitive-learning formulation of youth anxiety: a narrative review of theory and evidence and implications for treatment. Clin Psychol Rev. 2016;50:50–66 This recent narrative review provides a novel cognitive-learning framework to understanding anxiety disorders, integrating theoretical and empirical insights from cognitive and conditioning research. CrossRefGoogle Scholar
  21. 21.
    McTeague LM, Lang PJ. The anxiety spectrum and the reflex physiology of defense: from circumscribed fear to broad distress. Depress Anxiety. 2012;29(4):264–81.CrossRefGoogle Scholar
  22. 22.
    Friedman BH. An autonomic flexibility–neurovisceral integration model of anxiety and cardiac vagal tone. Biol Psychol. 2007;74(2):185–99.CrossRefGoogle Scholar
  23. 23.
    Kirschbaum C, Pirke K-M, Hellhammer DH. The ‘Trier social stress test’–a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28(1–2):76–81.CrossRefGoogle Scholar
  24. 24.
    Vaidyanathan U, Patrick CJ, Cuthbert BN. Linking dimensional models of internalizing psychopathology to neurobiological systems: affect-modulated startle as an indicator of fear and distress disorders and affiliated traits. Psychol Bull. 2009;135(6):909–42.CrossRefGoogle Scholar
  25. 25.
    McLaughlin KA, Sheridan MA, Gold AL, Duys A, Lambert HK, Peverill M, et al. Maltreatment exposure, brain structure, and fear conditioning in children and adolescents. Neuropsychopharmacology. 2016;41(8):1956–64.CrossRefGoogle Scholar
  26. 26.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.) 2013.Google Scholar
  27. 27.
    Wannemueller A, Adolph D, Joehren H-P, Blackwell SE, Margraf J. Psychophysiological reactivity of currently dental phobic-, remitted dental phobic-and never-dental phobic individuals during exposure to dental-related and other affect-inducing materials. Behav Res Ther. 2017;90:76–86.CrossRefGoogle Scholar
  28. 28.
    Sánchez-Navarro JP, Martínez-Selva JM, Maldonado EF, Carrillo-Verdejo E, Pineda S, Torrente G. Autonomic reactivity in blood-injection-injury and snake phobia. J Psychosom Res. 2018;115:117–24.CrossRefGoogle Scholar
  29. 29.
    • Diemer J, Lohkamp N, Mühlberger A, Zwanzger P. Fear and physiological arousal during a virtual height challenge—effects in patients with acrophobia and healthy controls. J Anxiety Disord. 2016;37:30–9 This study finds that height phobic and healthy largely did not differ in the physiological arousal during a VR height exposure, however the phobic group self-reported more fear. CrossRefGoogle Scholar
  30. 30.
    Notzon S, Deppermann S, Fallgatter A, Diemer J, Kroczek A, Domschke K, et al. Psychophysiological effects of an iTBS modulated virtual reality challenge including participants with spider phobia. Biol Psychol. 2015;112:66–76.CrossRefGoogle Scholar
  31. 31.
    Schumacher S, Miller R, Fehm L, Kirschbaum C, Fydrich T, Ströhle A. Therapists’ and patients’ stress responses during graduated versus flooding in vivo exposure in the treatment of specific phobia: a preliminary observational study. Psychiatry Res. 2015;230(2):668–75.CrossRefGoogle Scholar
  32. 32.
    Kotianova A, Kotian M, Slepecky M, Chupacova M, Prasko J, Tonhajzerova I. The differences between patients with panic disorder and healthy controls in psychophysiological stress profile. Neuropsychiatr Dis Treat. 2018;14:435–41.CrossRefGoogle Scholar
  33. 33.
    Choi KW, Jang EH, Kim AY, Fava M, Mischoulon D, Papakostas GI, et al. Heart rate variability for treatment response between patients with major depressive disorder versus panic disorder: a 12-week follow-up study. J Affect Disord. 2019;246:157–65.CrossRefGoogle Scholar
  34. 34.
    Katz AC, Weinberg A, Gorka SM, Auerbach RP, Shankman SA. Effect of comorbid post-traumatic stress disorder and panic disorder on defensive responding. 2017.Google Scholar
  35. 35.
    • Cooper SE, Grillon C, Lissek S. Impaired discriminative fear conditioning during later training trials differentiates generalized anxiety disorder, but not panic disorder, from healthy control participants. Compr Psychiatry. 2018;85:84–93 This study finds both PD and GAD demonstrated impaired discrimination between danger and safety cues compared to controls, however these errors were sustained for longer in GAD than PD and healthy controls, suggesting greater inflexibility in psychophysiological reactivity in GAD compared to PD. CrossRefGoogle Scholar
  36. 36.
    Petrowski K, Wichmann S, Siepmann T, Wintermann G-B, Bornstein SR, Siepmann M. Effects of mental stress induction on heart rate variability in patients with panic disorder. Appl Psychophysiol Biof. 2017;42(2):85–94.CrossRefGoogle Scholar
  37. 37.
    Petrowski K, Wintermann G-B, Kirschbaum C, Strahler J. Salivary alpha-amylase response following repeated psychosocial stress in patients with panic disorder. J Anxiety Disord. 2016;37:54–63.CrossRefGoogle Scholar
  38. 38.
    Wichmann S, Kirschbaum C, Lorenz T, Petrowski K. Effects of the cortisol stress response on the psychotherapy outcome of panic disorder patients. Psychoneuroendocrinology. 2017;77:9–17.CrossRefGoogle Scholar
  39. 39.
    Wintermann G-B, Kirschbaum C, Petrowski K. Predisposition or side effect of the duration: the reactivity of the HPA-axis under psychosocial stress in panic disorder. Int J Psychophysiol. 2016;107:9–15.CrossRefGoogle Scholar
  40. 40.
    Garcia-Leal C, Parente AC, Del-Ben CM, Guimarães FS, Moreira AC, Elias LLK, et al. Anxiety and salivary cortisol in symptomatic and nonsymptomatic panic patients and healthy volunteers performing simulated public speaking. Psychiatry Res. 2005;133(2–3):239–52.CrossRefGoogle Scholar
  41. 41.
    Petrowski K, Herold U, Joraschky P, Wittchen H-U, Kirschbaum C. A striking pattern of cortisol non-responsiveness to psychosocial stress in patients with panic disorder with concurrent normal cortisol awakening responses. Psychoneuroendocrinology. 2010;35(3):414–21.CrossRefGoogle Scholar
  42. 42.
    •• Alkozei A, Creswell C, Cooper PJ, Allen JJ. Autonomic arousal in childhood anxiety disorders: associations with state anxiety and social anxiety disorder. J Affect Disord. 2015;175:25–33 This study finds that children with SAD and children without SAD exhibited no differences in physiological reactivity, suggesting that children may not yet demonstrate the inflexible responding often reported in adults with SAD. CrossRefGoogle Scholar
  43. 43.
    Myllyneva A, Ranta K, Hietanen JK. Psychophysiological responses to eye contact in adolescents with social anxiety disorder. Biol Psychol. 2015;109:151–8.CrossRefGoogle Scholar
  44. 44.
    Keil V, Hepach R, Vierrath S, Caffier D, Tuschen-Caffier B, Klein C, et al. Children with social anxiety disorder show blunted pupillary reactivity and altered eye contact processing in response to emotional faces: insights from pupillometry and eye movements. J Anxiety Disord. 2018;58:61–9.CrossRefGoogle Scholar
  45. 45.
    Ketay S, Welker KM, Beck LA, Thorson KR, Slatcher RB. Social anxiety, cortisol, and early-stage friendship. J Soc Pers Relat. 2018. Scholar
  46. 46.
    García-Rubio MJ, Espín L, Hidalgo V, Salvador A, Gómez-Amor J. Autonomic markers associated with generalized social phobia symptoms: heart rate variability and salivary alpha-amylase. Stress. 2017;20(1):61–8.CrossRefGoogle Scholar
  47. 47.
    Carnevali L, Mancini M, Koenig J, Makovac E, Watson DR, Meeten F, et al. Cortical morphometric predictors of autonomic dysfunction in generalized anxiety disorder. Auton Neurosci. 2019;217:41–8.CrossRefGoogle Scholar
  48. 48.
    Shinba T. Major depressive disorder and generalized anxiety disorder show different autonomic dysregulations revealed by heart-rate variability analysis in first-onset drug-naïve patients without comorbidity. Psychiatry Clin Neurosci. 2017;71(2):135–45.CrossRefGoogle Scholar
  49. 49.
    Seeley SH, Mennin DS, Aldao A, McLaughlin KA, Rottenberg J, Fresco DM. Impact of comorbid depressive disorders on subjective and physiological responses to emotion in generalized anxiety disorder. Cogn Ther Res. 2016;40(3):290–303.CrossRefGoogle Scholar
  50. 50.
    Levine JC, Fleming R, Piedmont JI, Cain SM, Chen W-J. Heart rate variability and generalized anxiety disorder during laboratory-induced worry and aversive imagery. J Affect Disord. 2016;205:207–15.CrossRefGoogle Scholar
  51. 51.
    • Kircanski K, Waugh CE, Camacho MC, Gotlib IH. Aberrant parasympathetic stress responsivity in pure and co-occurring major depressive disorder and generalized anxiety disorder. J Psychopathol Behav Assess. 2016;38(1):5–19 This study finds no differences in HRV responsivity to a stressor between GAD, MDD, and comorbid GAD-MDD, suggesting a similar pattern of impaired, inflexible psychophysiological responding between these distress disorders. CrossRefGoogle Scholar
  52. 52.
    •• Pan X, Wang Z, Wu X, Wen SW, Liu A. Salivary cortisol in post-traumatic stress disorder: a systematic review and meta-analysis. BMC Psychiatry. 2018;18(1):324 This review is the most recent meta-analysis of salivary cortisol in PTSD, and clarifies inconsistent results reported previously, finding a trend of lower salivary cortisol in PTSD compared to controls. CrossRefGoogle Scholar
  53. 53.
    Campbell AA, Wisco BE, Silvia PJ, & Gay NG. Resting respiratory sinus arrhythmia and posttraumatic stress disorder: A meta-analysis. Biol. Psychol. 2019;144:125–135.Google Scholar
  54. 54.
    Jenness JL, Miller AB, Rosen ML, McLaughlin KA. Extinction learning as a potential mechanism linking high vagal tone with lower PTSD symptoms among abused youth. J Abnorm Child Psychol. 2018;47:659–670.CrossRefGoogle Scholar
  55. 55.
    Park JE, Lee JY, Kang S-H, Choi JH, Kim TY, So HS, et al. Heart rate variability of chronic posttraumatic stress disorder in the Korean veterans. Psychiatry Res. 2017;255:72–7.CrossRefGoogle Scholar
  56. 56.
    Dennis PA, Dedert EA, Van Voorhees EE, Watkins LL, Hayano J, Calhoun PS, et al. Examining the crux of autonomic dysfunction in PTSD: whether chronic or situational distress underlies elevated heart rate and attenuated heart-rate variability. Psychosom Med. 2016;78(7):805–9.CrossRefGoogle Scholar
  57. 57.
    Hinrichs R, Michopoulos V, Winters S, Rothbaum AO, Rothbaum BO, Ressler KJ, et al. Mobile assessment of heightened skin conductance in posttraumatic stress disorder. Depress Anxiety. 2017;34(6):502–7.CrossRefGoogle Scholar
  58. 58.
    van’t Wout M, Spofford CM, Unger WS, Sevin EB, Shea MT. Skin conductance reactivity to standardized virtual reality combat scenes in veterans with PTSD. Appl Psychophysiol Biof. 2017;42(3):209–21.CrossRefGoogle Scholar
  59. 59.
    Kirsch V, Wilhelm FH, Goldbeck L. Psychophysiological characteristics of pediatric posttraumatic stress disorder during script-driven traumatic imagery. Eur J Psychotraumatol. 2015;6(1):25471.CrossRefGoogle Scholar
  60. 60.
    • Quevedo K, Johnson AE, Loman MM, Lafavor T, Moua B, Gunnar MR. The impact of early neglect on defensive and appetitive physiology during the pubertal transition: a study of startle and postauricular reflexes. Dev Psychobiol. 2015;57(3):289–304 This study finds early neglect is associated with hypoactive reactivity to threat in later childhood. CrossRefGoogle Scholar
  61. 61.
    Schiweck C, Piette D, Berckmans D, Claes S, Vrieze E. Heart rate and high frequency heart rate variability during stress as biomarker for clinical depression. A systematic review. Psychol Med. 2019;49(2):200–11.CrossRefGoogle Scholar
  62. 62.
    Koenig J, Kemp AH, Beauchaine TP, Thayer JF, Kaess M. Depression and resting state heart rate variability in children and adolescents—a systematic review and meta-analysis. Clin Psychol Rev. 2016;46:136–50.CrossRefGoogle Scholar
  63. 63.
    Yancey JR, Vaidyanathan U, Patrick CJ. Aversive startle potentiation and fear pathology: mediating role of threat sensitivity and moderating impact of depression. Int J Psychophysiol. 2015;98(2):262–9.CrossRefGoogle Scholar
  64. 64.
    Dekel S, Ein-Dor T, Rosen JB, Bonanno GA. Differences in cortisol response to trauma activation in individuals with and without comorbid PTSD and depression. Front Psychol. 2017;8:797.CrossRefGoogle Scholar
  65. 65.
    Gonçalves R, Rodrigues H, Novaes F, Arbol J, Volchan E, Coutinho ESF, et al. Listening to the heart: a meta-analysis of cognitive behavior therapy impact on the heart rate of patients with anxiety disorders. J Affect Disord. 2015;172:231–40.CrossRefGoogle Scholar
  66. 66.
    Wendt J, Hamm AO, Pané-Farré CA, Thayer JF, Gerlach A, Gloster AT, et al. Pretreatment cardiac vagal tone predicts dropout from and residual symptoms after exposure therapy in patients with panic disorder and agoraphobia. Psychother Psychosom. 2018;87(3):187–9.CrossRefGoogle Scholar
  67. 67.
    Goessl VC, Curtiss JE, Hofmann SG. The effect of heart rate variability biofeedback training on stress and anxiety: a meta-analysis. Psychol Med. 2017;47(15):2578–86.CrossRefGoogle Scholar
  68. 68.
    Gorka S, Klumpp H, Ajilore O, Francis J, Craske M, Langenecker S, et al. 327. Startle reactivity to unpredictable threat as a psychophysiological treatment target for fear-based anxiety disorders. Biol Psychiatry. 2017;81(10):S134.CrossRefGoogle Scholar
  69. 69.
    Keefe JR, Guo W, Li QS, Amsterdam JD, Mao JJ. An exploratory study of salivary cortisol changes during chamomile extract therapy of moderate to severe generalized anxiety disorder. J Psychiatr Res. 2018;96:189–95.CrossRefGoogle Scholar
  70. 70.
    •• Lang PJ, McTeague LM, Bradley MM. RDoC, DSM, and the reflex physiology of fear: a biodimensional analysis of the anxiety disorders spectrum. Psychophysiology. 2016;53(3):336–47. This paper presents research on anxiety disorders conducted from the Research Domain Crieria (RDoc) framework, a new research initiative for studying mental illness proposed by the National Institute of Mental Health (NIMH). This framework employs multiple “units of analysis” including molecular, cellular, physiology and self-report measures. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Lang PJ, McTeague LM, Bradley MM. The psychophysiology of anxiety and mood disorders. Z Psychol. 2017;225:175–88.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jamiah Hyde
    • 1
  • Katherine M. Ryan
    • 1
  • Allison M. Waters
    • 1
    Email author
  1. 1.School of Applied PsychologyGriffith UniversityMt. GravattAustralia

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