Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T10:54:46.916Z Has data issue: false hasContentIssue false
  • English
  • Français

Reduced optimism and a heightened neural response to everyday worries are specific to generalized anxiety disorder, and not seen in social anxiety

Published online by Cambridge University Press:  14 March 2017

K. S. Blair ,
M. Otero ,
C. Teng ,
M. Geraci ,
M. Ernst ,
R. J. R. Blair ,
D. S. Pine  and
C. Grillon
K. S. Blair*
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA
M. Otero
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
C. Teng
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
M. Geraci
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
M. Ernst
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
R. J. R. Blair
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
D. S. Pine
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
C. Grillon
Affiliation:
Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
*
*Address for correspondence: K. S. Blair, Ph.D., Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, 15 K North Drive, Room 115A, MSC 2670, Bethesda, MD 20892-2670, USA. (Email: peschark@mail.nih.gov)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder.

Method

Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future.

Results

As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both).

Conclusions

The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.

Keywords

Functional magnetic resonance imaginggeneralized anxiety disordermedial prefrontal cortexsocial anxiety disorderworry
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 10 , July 2017 , pp. 1806 - 1815
Creative Commons
This is a work of the U.S. Government and is not subject to copyright protection in the United States.
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

Alexander, WH, Brown, JW (2011). Medial prefrontal cortex as an action-outcome predictor. Nature Neuroscience 14, 1338–1344.CrossRefGoogle ScholarPubMed
Ballard, K, Knutson, B (2009). Dissociable neural representations of future reward magnitude and delay during temporal discounting. NeuroImage 45, 143–150.CrossRefGoogle ScholarPubMed
Blair, KS, Geraci, M, Hollon, N, DeVido, J, Otero, M, Blair, RJR, Pine, DS (2012 a). Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia (GSP), generalized anxiety disorder (GAD) and comorbid GSP/GAD. Biological Psychiatry 15, 476–482.Google Scholar
Blair, KS, Geraci, M, Hollon, N, Otero, M, DeVido, J, Majestic, C, Jacobs, M, Blair, RJ, Pine, DS (2010). Social norm processing in adult social phobia: atypically increased ventromedial frontal cortex responsiveness to unintentional (embarrassing) transgressions. American Journal of Psychiatry 167, 1526–1532.Google Scholar
Blair, KS, Geraci, M, Otero, M, Majestic, C, Odenheimer, S, Jacobs, M, Blair, RJ, Pine, DS (2011). Atypical modulation of medial prefrontal cortex to self-referential comments in generalized social phobia. Psychiatry Research 193, 38–45.Google Scholar
Blair, KS, Geraci, M, Smith, BW, Hollon, N, Devido, J, Otero, M, Blair, JR, Pine, DS (2012 b). Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia, generalized anxiety disorder, and comorbid generalized social phobia/generalized anxiety disorder. Biological Psychiatry 72, 476–482.Google Scholar
Blair, KS, Marsh, AA, Morton, J, Vythilingham, M, Jones, M, Mondillo, K, Pine, DS, Drevets, WC, Blair, RJR (2006). Choosing the lesser of two evils, the better of two goods: specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate cortex in object choice. Journal of Neuroscience 26, 11379–11386.Google Scholar
Blair, KS, Otero, M, Teng, C, Jacobs, M, Odenheimer, S, Pine, DS, Blair, RJ (2013). Dissociable roles of ventromedial prefrontal cortex (vmPFC) and rostral anterior cingulate cortex (rACC) in value representation and optimistic bias. NeuroImage 78, 103–110.Google Scholar
Britton, JC, Grillon, C, Lissek, S, Norcross, MA, Szuhayny, KL, Chen, G, Ernst, M, Nelson, EE, Leibenluft, MD, Shechner, T, Pine, DS (2013). Response to learned threat: an fMRI study in adolescent and adult anxiety. American Journal of Psychiatry 170, 1195–1204.Google Scholar
Campbell-Sills, L, Simmons, AN, Lovero, KL, Rochlin, AA, Paulus, MP, Stein, MB (2011). Functioning of neural systems supporting emotion regulation in anxiety-prone individuals. NeuroImage 54, 689–696.Google Scholar
Cox, RW (1996). AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research 29, 162–173.Google Scholar
Craske, MG, Rauch, SL, Ursano, R, Prenoveau, J, Pine, DS, Zinbarg, RE (2009). What is an anxiety disorder? Depression and Anxiety 26, 1066–1085.Google Scholar
Etkin, A, Prater, KE, Hoeft, F, Menon, V, Schatzberg, AF (2010). Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. American Journal of Psychiatry 167, 545–554.Google Scholar
Etkin, A, Schatzberg, AF (2011). Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders. American Journal of Psychiatry 168, 968–978.CrossRefGoogle ScholarPubMed
First, M, Spitzer, R, Gibbon, M, Williams, J (1997). Structured Clinical Interview for DSM-IV. American Psychiatric Press: Washington, DC.Google Scholar
Helweg-Larsen, M, Shepperd, JA (2001). Do moderators of the optimistic bias affect personal or target risk estimates? A review of the literature. Personality and Social Psychology Review 5, 74–95.CrossRefGoogle Scholar
Kerns, JG, Cohen, JD, MacDonald, AW, Cho, RY, Stenger, VA, Carter, CS (2004). Anterior cingulate conflict monitoring and adjustments in control. Science 303, 1023–1026.Google Scholar
Krain, A, Gotimer, K, Hefton, S, Ernst, M, Castellanos, FX, Pine, DS, Milham, MP (2008). A functional magnetic resonance imaging investigation of uncertainty in adolescents with anxiety disorders. Biological Psychiatry 63, 563–568.Google Scholar
Levy, DJ, Glimcher, PW (2011). Comparing apples and oranges: using reward-specific and reward-general subjective value representation in the brain. Journal of Neuroscience 31, 14693–14707.CrossRefGoogle ScholarPubMed
Martin, EI, Ressler, KJ, Binder, E, Nemeroff, CB (2010). The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Clinical and Laboratory Medicine 30, 865–891.Google Scholar
McClure, EB, Monk, CS, Nelson, EE, Parrish, JM, Adler, A, Blair, RJ, Fromm, S, Charney, DS, Leibenluft, E, Ernst, M, Pine, DS (2007). Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Archives of General Psychiatry 64, 97–106.Google Scholar
Monk, CS, Nelson, EE, McClure, EB, Mogg, K, Bradley, BP, Leibenluft, E, Blair, RJ, Chen, G, Charney, DS, Ernst, M, Pine, DS (2006). Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. American Journal of Psychiatry 163, 1091–1097.CrossRefGoogle ScholarPubMed
Nitschke, JB, Sarinopoulos, I, Oathes, DJ, Johnstone, T, Whalen, PJ, Davidson, RJ, Kalin, NH (2009). Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. American Journal of Psychiatry 166, 302–310.CrossRefGoogle ScholarPubMed
Paulesu, E, Sambugaro, E, Torti, T, Danelli, L, Ferri, F, Scialfa, G, Sberna, M, Ruggiero, GM, Bottini, G, Sassaroli, S (2010). Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study. Psychological Medicine 40, 117–124.Google Scholar
Sharot, T, Kanai, R, Marston, D, Korn, CW, Rees, G, Dolan, RJ (2012). Selectively altering belief formation in the human brain. Proceedings of the National Academy of Sciences of the United States of America 109, 17058–17062.Google Scholar
Sharot, T, Korn, CW, Dolan, RJ (2011). How unrealistic optimism is maintained in the face of reality. Nature Neuroscience 14, 1475–1479.Google Scholar
Sharot, T, Riccardi, AM, Raio, CM, Phelps, EA (2007). Neural mechanisms mediating optimism bias. Nature 450, 102–106.CrossRefGoogle ScholarPubMed
Strunk, DR, Lopez, H, DeRubeis, RJ (2006). Depressive symptoms are associated with unrealistic negative predictions of future life events. Behavior Research and Therapy 44, 861–882.CrossRefGoogle ScholarPubMed
Talairach, J, Tournoux, P (1988). Co-planar Stereotaxic Atlas of the Human Brain. Thieme: Stuttgart.Google Scholar
Weinstein, ND (1980). Unrealistic optimism about future life events. Journal of Personality and Social Psychology 39, 806–820.Google Scholar
Whalen, PJ, Johnstone, T, Somerville, LH, Nitschke, JB, Polis, S, Alexander, AL, Davidson, RJ, Kalin, NH (2008). A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biological Psychiatry 63, 858–863.Google Scholar
White, SF, Geraci, M, Lewis, E, Leshin, J, Teng, C, Averbeck, B, Meffert, H, Ernst, M, Blair, RJ, Grillon, C, Blair, KS (2017). Prediction error representation in patients with generalized anxiety disorder during passive avoidance. American Journal of Psychiatry 174, 110–117.Google Scholar