Skip to main content

Abstract

Objective

Poor threat-safety discrimination reflects prefrontal cortex dysfunction in adult anxiety disorders. While adolescent anxiety disorders are impairing and predict high risk for adult anxiety disorders, the neural correlates of threat-safety discrimination have not been investigated in this population. The authors compared prefrontal cortex function in anxious and healthy adolescents and adults following conditioning and extinction, processes requiring threat-safety learning.

Method

Anxious and healthy adolescents and adults (N=114) completed fear conditioning and extinction in the clinic. The conditioned stimuli (CS+) were neutral faces, paired with an aversive scream. Physiological and subjective data were acquired. Three weeks later, 82 participants viewed the CS+ and morphed images resembling the CS+ in an MRI scanner. During scanning, participants made difficult threat-safety discriminations while appraising threat and explicit memory of the CS+.

Results

During conditioning and extinction, the anxious groups reported more fear than the healthy groups, but the anxious adolescent and adult groups did not differ on physiological measures. During imaging, both anxious adolescents and adults exhibited lower activation in the subgenual anterior cingulate cortex than their healthy counterparts, specifically when appraising threat. Compared with their age-matched counterpart groups, anxious adults exhibited reduced activation in the ventromedial prefrontal cortex when appraising threat, whereas anxious adolescents exhibited a U-shaped pattern of activation, with greater activation in response to the most extreme CS+ and CS–.

Conclusions

Two regions of the prefrontal cortex are involved in anxiety disorders. Reduced subgenual anterior cingulate cortex engagement is a shared feature in adult and adolescent anxiety disorders, but ventromedial prefrontal cortex dysfunction is age-specific. The unique U-shaped pattern of activation in the ventromedial prefrontal cortex in many anxious adolescents may reflect heightened sensitivity to threat and safety conditions. How variations in the pattern relate to later risk for adult illness remains to be determined.

Formats available

You can view the full content in the following formats:

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1195 - 1204
PubMed: 23929092

History

Received: 19 May 2012
Revision received: 30 August 2012
Accepted: 25 March 2013
Published online: 1 October 2013
Published in print: October 2013

Authors

Details

Jennifer C. Britton, Ph.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Christian Grillon, Ph.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Shmuel Lissek, Ph.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Maxine A. Norcross, B.S.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Kristin L. Szuhany, B.S.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Gang Chen, Ph.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Monique Ernst, M.D., Ph.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Eric E. Nelson, Ph.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Ellen Leibenluft, M.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Tomer Shechner, Ph.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.
Daniel S. Pine, M.D.
From the Department of Psychology, University of Miami, Coral Gables, Fla.; the National Institute of Mental Health, Bethesda, Md.; Department of Psychology, University of Minnesota, Minneapolis; School of Medicine, Johns Hopkins University, Baltimore; and Department of Psychology, Boston University, Boston.

Notes

Presented at the annual meeting of the American College of Neuropsychopharmacology, Miami Beach, Fla., Dec. 5–9, 2010, and Waikoloa, Hawaii, Dec. 4–8, 2011; and the annual meeting of the Anxiety and Depression Association of America, Baltimore, March 4–7, 2010, and New Orleans, March 24–27, 2011.
Address correspondence to Dr. Britton ([email protected]).

Funding Information

The authors report no financial relationships with commercial interests.
Supplementary Material

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard

View Options

View options

PDF/ePub

View PDF/ePub

Full Text

View Full Text

Get Access

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Purchase Options

Purchase this article to access the full text.

PPV Articles - American Journal of Psychiatry

PPV Articles - American Journal of Psychiatry

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share