Hostname: page-component-848d4c4894-pftt2 Total loading time: 0 Render date: 2024-05-09T20:31:30.731Z Has data issue: false hasContentIssue false
  • English
  • Français

Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders

Published online by Cambridge University Press:  24 April 2017

S. M. Gorka ,
L. Lieberman ,
H. Klumpp ,
K. L. Kinney ,
A. E. Kennedy ,
O. Ajilore ,
J. Francis ,
J. Duffecy ,
M. G. Craske  and
J. Nathan
...Show all authors
S. M. Gorka*
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA
L. Lieberman
Affiliation:
Department of Psychology, University of Illinois-Chicago, 1007 West Harrison St. (M/C 285) Chicago, IL 60607, USA
H. Klumpp
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA
K. L. Kinney
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA Department of Psychology, University of Illinois-Chicago, 1007 West Harrison St. (M/C 285) Chicago, IL 60607, USA
A. E. Kennedy
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA Jesse Brown VA Medical Center, Mental Health Service Line, 820 S. Damen Avenue Chicago, IL 60612, USA
O. Ajilore
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA
J. Francis
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA
J. Duffecy
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA
M. G. Craske
Affiliation:
Department of Psychology, University of California, Los Angeles, Franz Hall – Box 95156 Los Angeles, CA 90094, USA
J. Nathan
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA
S. Langenecker
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA
S. A. Shankman
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA Department of Psychology, University of Illinois-Chicago, 1007 West Harrison St. (M/C 285) Chicago, IL 60607, USA
K. L. Phan
Affiliation:
Department of Psychiatry, University of Illinois-Chicago, 1747 West Roosevelt Road Chicago, IL 60608, USA Department of Psychology, University of Illinois-Chicago, 1007 West Harrison St. (M/C 285) Chicago, IL 60607, USA Jesse Brown VA Medical Center, Mental Health Service Line, 820 S. Damen Avenue Chicago, IL 60612, USA Department of Anatomy and Cell Biology & the Graduate Program in Neuroscience, University of Illinois-Chicago, 808 S. Wood Street Chicago, IL 60612, USA
*
*Address for correspondence: S. M. Gorka, Ph.D., Department of Psychiatry, University of Illinois atChicago, 1747 Roosevelt Road, Chicago, IL 60608, USA. (Email: sgorka2@uic.edu)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT).

Methods

Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding.

Results

Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable.

Conclusions

Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.

Keywords

Anxietydistressfearstartle potentiationtemporal stabilityunpredictable threat
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 14 , October 2017 , pp. 2450 - 2460
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aiken, LS, West, SG, Reno, RR (1991). Multiple Regression: Testing and Interpreting Interactions. Sage: Newbury Park, CA.Google Scholar
Alvarez, RP, Chen, G, Bodurka, J, Kaplan, R, Grillon, C (2011). Phasic and sustained fear in humans elicits distinct patterns of brain activity. Neuroimage 1, 389–400.CrossRefGoogle Scholar
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5. American Psychiatric Association: Washington, DC.Google Scholar
Barlow, DH (2000). Unraveling the mysteries of anxiety and its disorders from the perspective of emotion theory. American Psychologist 55, 1247–1263.Google Scholar
Barlow, DH, Craske, MG (2006). Mastery of your Anxiety and Panic. Oxford University Press: New York.Google Scholar
Beck, AT (1979). Cognitive Therapy of Depression. Guilford Press: New York.Google Scholar
Blumenthal, TD, Cuthbert, BN, Filion, DL, Hackley, S, Lipp, OV, van Boxtel, A (2005). Committee report: guidelines for human startle eyeblink electromyographic studies. Psychophysiology 42, 1–15.CrossRefGoogle ScholarPubMed
Bradley, MM, Cuthbert, BN, Lang, PJ (1999). Affect and the startle reflex. In Startle Modification: Implication for Neuroscience, Cognitive Science, and Clinical Science (ed. Dawson, M.E., Schell, A.M. and Bohmet, A.H.), pp. 157–193. Cambridge University Press: New York.CrossRefGoogle Scholar
Butler, AC, Chapman, JE, Forman, EM, Beck, AT (2006). The empirical status of cognitive-behavioral therapy: a review of meta-analyses. Clinical Psychology Review 26, 17–31.Google Scholar
Carleton, RN (2012). The intolerance of uncertainty construct in the context of anxiety disorders: theoretical and practical perspectives. Expert Review of Neurotheraputics 12, 937–947.Google Scholar
Carleton, RN (2016 a). Fear of the unknown: one fear to rule them all? Journal of Anxiety Disorders 41, 5–21.Google Scholar
Carleton, RN (2016 b). Into the Unknown: a review and synthesis of contemporary models involving uncertainty. Journal of Anxiety Disorders 39, 30–43.Google Scholar
Clark, LA, Watson, D (2006). Distress and fear disorders: an alternative empirically based taxonomy of the ‘mood'and ‘anxiety'disorders. British Journal of Psychiatry 189, 481–483.Google Scholar
Cuthbert, BN, Kozak, MJ (2013). Constructing constructs for psychopathology: the NIMH research domain criteria. Journal of Abnormal Psychology 122, 928–937.Google Scholar
Craske, MG, Barlow, DH, O'Leary, TA (1992). Mastery of your Anxiety and Worry. Graywind Publications: Albany.Google Scholar
Davis, M (1998). Are different parts of the extended amygdala involved in fear versus anxiety? Biological Psychiatry 44, 1239–1247.Google Scholar
Davis, M (2006). Neural systems involved in fear and anxiety measured with fear-potentiated startle. American Psychologist 61, 741–756.Google Scholar
Davis, M, Walker, DL, Miles, L, Grillon, C (2010). Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105–135.Google Scholar
Gorka, SM, Lieberman, L, Shankman, SA, Phan, KL (2016). Startle potentiation to uncertain threat as a psychophysiological indicator of fear-based psychopathology: an examination across multiple internalizing disorders. Journal of Abnormal Psychology 126, 8–18.Google Scholar
Gorka, SM, Nelson, BD, Phan, KL, Shankman, SA (2014). Insula response to unpredictable and predictable aversiveness in individuals with panic disorder and comorbid depression. Biology of Mood and Anxiety Disorders 4, 1.CrossRefGoogle ScholarPubMed
Gorka, SM, Nelson, BD, Shankman, SA (2013). Startle response to unpredictable threat in comorbid panic disorder and alcohol dependence. Drug and Alcohol Dependence 132, 216–222.CrossRefGoogle ScholarPubMed
Grillon, C, Baas, JP, Lissek, S, Smith, K, Milstein, J (2004). Anxious responses to predictable and unpredictable aversive events. Behavioral Neuroscience 118, 916–924.CrossRefGoogle ScholarPubMed
Grillon, C, Baas, JM, Pine, DS, Lissek, S, Lawley, M, Ellis, V, Levine, J (2006). The benzodiazepine alprazolam dissociates contextual fear from cued fear in humans as assessed by fear-potentiated startle. Biological Psychiatry 60, 760–766.Google Scholar
Grillon, C, Chavis, C, Covington, MF, Pine, DS (2009 a). Two-week treatment with the selective serotonin reuptake inhibitor citalopram reduces contextual anxiety but not cued fear in healthy volunteers: a fear-potentiated startle study. Neuropsychopharmacology 34, 964–971.Google Scholar
Grillon, C, Heller, R, Hirschhorn, E, Kling, MA, Pine, DS, Schulkin, J, Vythilingam, M (2011). Acute hydrocortisone treatment increases anxiety but not fear in healthy volunteers: a fear-potentiated startle study. Biological Psychiatry 69, 549–555.Google Scholar
Grillon, C, Lissek, S, Rabin, S, McDowell, D, Dvir, S, Pine, DS (2008). Increased anxiety during anticipation of unpredictable but not predictable aversive stimuli as psychophysiologic marker of panic disorder. American Journal of Psychiatry 165, 898–904.Google Scholar
Grillon, C, Pine, DS, Lissek, S, Rabin, S, Bonne, O, Vythilingam, M (2009 b). Increased anxiety during anticipation of unpredictable aversive stimuli in posttraumatic stress disorder but not in generalized anxiety disorder. Biological Psychiatry 66, 47–53.Google Scholar
Grupe, DW, Nitschke, JB (2013). Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nature Reviews Neuroscience 14, 488–501.Google Scholar
Guy, W (1976). ECDEU Assessment Manual for Psychopharmacology. US Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs: Rockville, MD, Vol. 76, No. 338.Google Scholar
Hamilton, M (1959). The assesment of anxiety states by rating. British Journal of Medical Psychology 32, 50–55.Google Scholar
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, & Psychiatry 23, 56–62.CrossRefGoogle ScholarPubMed
Hettema, JM, Prescott, CA, Myers, JM, Neale, MC, Kendler, KS (2005). The structure of genetic and environmental risk factors for anxiety disorders in men and women. Archives of General Psychiatry 62, 182–189.Google Scholar
Hieronymus, F, Emilsson, JF, Nilsson, S, Eriksson, E (2016). Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression. Molecular Psychiatry 21, 523–530.CrossRefGoogle ScholarPubMed
Johnsen, TJ, Friborg, O (2015). The effects of cognitive behavioral therapy as an anti-depressive treatment Is falling: a meta-analysis. Psychological Bulletin 141, 747–768.Google Scholar
Kaye, JT, Bradford, DE, Curtin, JJ (2016). Psychometric properties of startle and corrugator response in NPU, affective picture viewing, and resting state tasks. Psychophysiology 53, 1241–1255.Google Scholar
Kendler, KS, Prescott, CA, Myers, J, Neale, MC (2003). The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Archives of General Psychiatry 60, 929–937.Google Scholar
Kennedy, SH, Konarski, JZ, Segal, ZV, Lau, MA, Bieling, PJ, McIntyre, RS, Mayberg, HS (2007). Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial. American Journal of Psychiatry 164, 778–788.CrossRefGoogle Scholar
Kozak, MJ, Cuthbert, BN (2016). The NIMH research domain criteria initiative: background, issues, and pragmatics. Psychophysiology 53, 286–297.Google Scholar
Lieberman, L, Gorka, SM, Shankman, SA, Phan, KL (2017). Impact of panic on psychophysiological and neural reactivity to unpredictable threat in depression and anxiety. Clinical Psychological Science 5, 52–63.Google Scholar
Lovibond, SH, Lovibond, PF (1995). Manual for the Depression Anxiety Stress scale, 2nd edn. Psychology Foundation: Sydney.Google Scholar
Morris, SE, Cuthbert, BN (2012). Research Domain Criteria: cognitive systems, neural circuits, and dimensions of behavior. Dialogues in Clinical Neuroscience 14, 29–37.CrossRefGoogle ScholarPubMed
Münsterkötter, AL, Notzon, S, Redlich, R, Grotegerd, D, Dohm, K, Arolt, V, Kugel, H, Zwanzger, P, Dannlowski, U (2015). Spider or no spider? Neural correlates of sustained and phasic fear in spider phobia. Depression and Anxiety 32, 656–663.Google Scholar
Nelson, BD, McGowan, SK, Sarapas, C, Robison-Andrew, EJ, Altman, SE, Campbell, ML, Gorka, SM, Katz, A, Shankman, SA (2013). Biomarkers of threat and reward sensitivity demonstrate unique associations with risk for psychopathology. Journal of Abnormal Psychology 122, 662–671.CrossRefGoogle ScholarPubMed
Sanislow, CA, Pine, DS, Quinn, KJ, Kozak, MJ, Garvey, MA, Heinssen, RK, Wang, PS, Cuthbert, BN (2010). Developing constructs for psychopathology research: research domain criteria. Journal of Abnormal Psychology 119, 631–639.CrossRefGoogle ScholarPubMed
Schmitz, A, Grillon, C (2012). Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test). Nature Protocols 7, 527–532.Google Scholar
Shankman, SA, Nelson, BD, Sarapas, C, Robison-Andrew, EJ, Campbell, ML, Altman, SE, McGowan, SK, Katz, AC, Gorka, SM (2013). A psychophysiological investigation of reward and threat sensitivity in individuals with depression and/or panic disorder. Journal of Abnormal Psychology 122, 322–338.Google Scholar
Simmons, AN, Flagan, TM, Wittmann, M, Strigo, IA, Matthews, SC, Donovan, H, Lohr, JB, Paulus, MP (2013). The effects of temporal unpredictability in anticipation of negative events in combat veterans with PTSD. Journal of Affective Disorders 146, 426–432.Google Scholar
Soto, CJ, Tackett, JL (2015). Personality traits in childhood and adolescence structure, development, and outcomes. Current Directions in Psychological Science 24, 358–362.Google Scholar
Watson, D (2009). Differentiating the mood and anxiety disorders: a quadripartite model. Annual Review of Clinical Psychology 5, 221–247.Google Scholar
Watson, D, O'Hara, MW, Naragon-Gainey, K, Koffel, E, Chmielewski, M, Kotov, R, Stasik, SM, Ruggero, CJ (2012). Development and validation of new anxiety and bipolar symptom scales for an expanded version of the IDAS (the IDAS-II). Assessment 19, 399–420.Google Scholar