Individual differences in fear-potentiated startle as a function of resting heart rate variability: Implications for panic disorder

https://doi.org/10.1016/j.ijpsycho.2008.07.013Get rights and content

Abstract

Background

Anticipatory anxiety, which can be indexed by the startle potentiation to a threat of shock, has been implicated in the development of panic disorder. Large individual differences exist in startle potentiation to threat of shock but few differences have been found between panic patients in general and non-anxious controls. The present studies explored resting heart rate variability (HRV) as a source of individual differences in startle potentiation in students at risk for panic disorder and in unmedicated panic patients.

Methods

Participants in Study 1 were 22 students high and 21 students low in anxiety sensitivity (AS). Nine unmedicated panic patients and 15 matched non-anxious controls were included in Study 2. Startle potentiation to the threat of shock was examined as a function of AS (Study 1) and diagnostic category (Study 2) as well as resting HRV.

Results

Whereas no differences in startle potentiation were found as a function of AS or panic disorder diagnosis in general, both studies revealed that low resting HRV was associated with exaggerated startle responses to the threat of shock.

Conclusions

The present results replicate and extend the sparse literature on fear-potentiated startle in panic disorder. Low HRV was associated with more pronounced startle potentiation to both explicit and contextual cues. Thus, low HRV may be a useful endophenotype for at least some anxiety disorders.

Introduction

Panic disorder affects between 3% and 5% of the population and is associated with severe behavioral and economic consequences (Wittchen and Jacobi, 2005). One of the prominent features of panic disorder is anxious apprehension which is the anticipation of potentially threatening events in the future (DSM-IV; American Psychiatric Association, 1994, Grillon, 2002). Moreover, there is an increasing appreciation of the role of anticipatory anxiety in the development of panic disorder (Bouton et al., 2001). Anticipatory anxiety is characterized by strong physiological arousal (increase in heart rate [Deane, 1961, Deane, 1969, Deane and Zeaman, 1958], respiratory rate [Masaoka and Homma, 2000, Masaoka and Homma, 2001], and skin conductance level [Chattopadhyay et al., 1980]), hypervigilance towards potential threat, excessive worry, uncertainty (Barlow, 2000, Grillon, 2002), and a clear potentiation of the startle reflex (Grillon et al., 1991, Grillon et al., 1993, Melzig et al., 2007). The latter finding is particularly important, because the potentiation of the acoustic startle reflex rather specifically indexes the activation of the mammalian defense system (for a review, see Lang et al., 2000). It has repeatedly been shown that the startle eyeblink response elicited by a brief acoustic probe stimulus is augmented during viewing of unpleasant pictures and is even further potentiated during viewing of phobia-relevant stimuli (Bradley, 2000, Hamm et al., 1997). Moreover, this potentiation of the startle reflex by anticipatory anxiety seems to operate on a very fundamental level outside of the participants' awareness and is mediated by the extended amygdala, a subcortical limbic structure located in the anterior temporal lobe (see Davis, 2000). Although, as explained above, anticipatory anxiety is considered a hallmark of panic disorder, few differences in anxiety-associated startle modulation have been found between panic patients and non-anxious controls when studied using threat of shock paradigms (Chattopadhyay et al., 1980, Grillon et al., 1994, Grillon, 2002, Melzig et al., 2007). However, the data collected in panic patients also indicate that there are large individual differences associated with the quality of emotional functioning, e.g., the severity of depression (Melzig et al., 2007). The present study was designed to explore further possible sources of individual differences in startle potentiation during threat of shock.

One individual difference factor that has recently been shown to influence startle magnitude and emotion-modulated startle is resting heart rate variability (Ruiz-Padial et al., 2003). It was reported that persons with low resting HRV showed potentiated startle responses to neutral foreground stimuli, which may be interpreted as a constant state of hypervigilance due to anticipation of adverse events in the environment. Thus, individual differences in resting HRV may influence the modulation of startle responses and this may also hold true for startle potentiation during anticipatory anxiety. Interestingly, lowered HRV has been linked to a number of physiological and psychological disorders and emotion regulation ability (see Thayer and Brosschot, 2005 for a review). Furthermore, it has been proposed that HRV reflects the level of inhibitory control of the prefrontal cortex, not only over sympathoexcitatory circuits but also over defensive networks (Thayer and Lane, 2000). Although there is an ongoing discussion that this prefrontal inhibitory control may even be critical for the development of pathological anxiety (Quirk and Gehlert, 2003) as found in panic disorder, to date HRV as a potential source of inter-individual variability in startle potentiation during anticipatory anxiety has not been examined.

In the present paper, we report the results of two studies in which we investigated the relationship between startle potentiation during anticipatory anxiety and the resting HRV of the participants. In the first study, persons were selected on the basis of their scores on a measure of anxiety sensitivity, an individual difference variable that has been shown to be associated with the future development of panic disorder (McNally, 2002, Hayward et al., 2000, Schmidt et al., 1997, Schmidt et al., 1999). In the second study, unmedicated patients with diagnosed panic disorder and matched controls were examined. Consistent with prior research, we expected that the low and high anxiety sensitivity groups as well as the panic disorder patients and matched controls would not differ overall on startle potentiation during threat of shock. However, we expected that independent of anxiety grouping or diagnostic categories, those persons with low resting HRV would show larger startle potentiation compared to those with high resting HRV.

Section snippets

Study 1 — Participants

Participants were recruited for a study evaluating the influence of anxiety sensitivity on physiological responding to diverse anticipation and symptom provocation tasks. Approximately 250 university students were screened with the Anxiety Sensitivity Index (ASI; Peterson and Reiss, 1992). Participants scoring either high or low (at least one standard deviation (9 points) from the mean (20 points)) on the ASI were contacted by telephone and screened for the following exclusion criteria:

Study 2 — Participants

Nine outpatients with panic disorder (7 women, mean age 34.2 years) were recruited for this study from the University of Greifswald Psychotherapy Clinic. In addition, 15 healthy control participants, matched for age and gender, who were not taking any medication (7 women, mean age: 34.6) and did not smoke were recruited through postings at diverse university facilities. Patients and controls were asked to take part in a psychophysiological study during which they would be exposed to different

Discussion

The results of the present experiments provide valuable insights into the nature of the individual differences in fear-potentiated startle responses. Whereas there was little evidence for differences in fear-potentiated startle responses due to anxiety sensitivity, a putative risk factor for the development of panic disorder (McNally, 2002), or for panic patients when compared to the control group as a whole, the results of the two studies showed that low resting HRV was associated with larger

Acknowledgments

This study was supported by the Department of Neuroscience at the University of Greifswald and by a grant from the federal government (Improving the Treatment of Panic Disorder 01GV0614).

The contribution of Julian F. Thayer was supported by a Senior Fellowship from the Krupp-Wissenschaftskolleg Greifswald.

References (75)

  • GrillonC. et al.

    Darkness facilitates the acoustic startle reflex in humans

    Biol. Psychiatry

    (1997)
  • HaywardC. et al.

    Predictors of panic attacks in adolescents

    J. Am. Acad. Child Adolesc. Psych.

    (2000)
  • LangP.J. et al.

    Fear and anxiety: animal models and human cognitive psychophysiology

    J. Affect. Disord.

    (2000)
  • MasaokaY. et al.

    The source generator of respiratory-related anxiety potential in the human brain

    Neurosci. Lett.

    (2000)
  • MasaokaY. et al.

    The effect of anticipatory anxiety on breathing and metabolism in humans

    Respir. Physiol.

    (2001)
  • McNallyR.J.

    Anxiety sensitivity and panic disorder

    Biol. Psychiatry

    (2002)
  • NiskanenJ.-P. et al.

    Software for advanced HRV analysis

    Comput. Methods Programs Biomed.

    (2004)
  • NitschkeJ.B. et al.

    Functional neuroanatomy of aversion and its anticipation

    NeuroImage

    (2006)
  • ThayerJ.F. et al.

    A model of neurovisceral integration in emotion regulation and dysregulation

    J. Affect. Disord.

    (2000)
  • ThayerJ.F. et al.

    Psychosomatics and psychopathology: looking up and down from the brain

    Psychoneuroendocrinology

    (2005)
  • ThayerJ.F. et al.

    Effect of angiotensin-converting enzyme insertion/deletion polymorphism DD genotype on high-frequency heart rate variability in African Americans

    Am. J. Cardiol.

    (2003)
  • WangX. et al.

    Ethnic differences and heritability of heart rate variability in African- and European American youth

    Am. J. Cardiol.

    (2005)
  • WittchenH.U. et al.

    Size and burden of mental disorders in Europe — a critical review and appraisal of 27 studies

    Eur. Neuropsychopharmacol.

    (2005)
  • American Psychiatric Association

    Diagnostic and Statistical Manual of Mental Disorders

    (1994)
  • AggletonJ.P. et al.

    The enigma of the amygdale: on its contribution to human emotion

  • AhernG.L. et al.

    Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test

    Epilepsia

    (2001)
  • BarlowD.H.

    Unraveling the mysteries of anxiety and its disorders from the perspective of emotion theory

    Am. Psychol.

    (2000)
  • BeckA.T. et al.

    Beck Depression Inventory — Manual

    (1987)
  • BoutonM.E. et al.

    A modern learning theory perspective on the etiology of panic disorder

    Psychol. Rev.

    (2001)
  • BradleyM.M.

    Emotion and motivation

  • BradleyM.M. et al.

    Measuring emotion: behaviour, feeling, and physiology

  • ChamblessD.L. et al.

    Assessment of fear of fear in agoraphobics: the body sensations questionnaire and the agoraphobic cognitions questionnaire

    J. Consult. Clin. Psychol.

    (1984)
  • ChattopadhyayP. et al.

    Habituation of physiological responses in anxiety

    Biol. Psychiatry

    (1980)
  • CookE.W. et al.

    Stimulus control and data acquisition for IBM PCs and compatibles

    Psychophysiology

    (1987)
  • CuthbertB.N. et al.

    The psychophysiology of anxiety disorder: fear memory imagery

    Psychophysiology

    (2003)
  • DavidsonR.J.

    Affective style, psychopathology, and resilience: brain mechanisms and plasticity

    Am. Psychol.

    (2000)
  • DavisM.

    The role of the amygdala in conditioned and unconditioned fear and anxiety

  • Cited by (100)

    • Resilience of the Hellenic navy seals assessed by heart rate variability during cognitive tasks

      2021, Physiology and Behavior
      Citation Excerpt :

      A salient example refers to the relationship between HRV and performance in the presence of emotional distractors (such as emotion stroop) [31]. Taken together our results display that HNS had equivalent performance with HC in cognitive and emotional tasks but recorded lower HRV (REPHRASE το κιτρινο-δεν βγαζει νοημα) These observations appear to be incompatible with the theory that higher HRV is associated with greater capacity for emotion regulation [13, 32] and with greater performance on several cognitive tasks involving attention, working memory, and inhibitory control [33]. The aforementioned discrepancy regarding higher levels of HRV and intact cognitive performance, could also be understood considering the cognitive efficiency notion and the physical exhaustion.

    View all citing articles on Scopus
    View full text