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Published Online: 1 May 2010

Failure of Anterior Cingulate Activation and Connectivity With the Amygdala During Implicit Regulation of Emotional Processing in Generalized Anxiety Disorder

Amit Etkin, M.D., Ph.D., Katherine E. Prater, B.A., Fumiko Hoeft, M.D., Ph.D., Vinod Menon, Ph.D., and Alan F. Schatzberg, M.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 167, Number 5
https://doi.org/10.1176/appi.ajp.2009.09070931
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Abstract

Objective

Clinical data suggest that abnormalities in the regulation of emotional processing contribute to the pathophysiology of generalized anxiety disorder, yet these abnormalities remain poorly understood at the neurobiological level. The authors recently reported that in healthy volunteers the pregenual anterior cingulate regulates emotional conflict on a trial-by-trial basis by dampening activity in the amygdala. The authors also showed that this process is specific to the regulation of emotional, compared to nonemotional, conflict. Here the authors examined whether this form of noninstructed emotion regulation is perturbed in generalized anxiety disorder.

Method

Seventeen patients with generalized anxiety disorder and 24 healthy comparison subjects underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. Behavioral and neural measures were used to compare trial-by-trial changes in conflict regulation.

Results

Comparison subjects effectively regulated emotional conflict from trial to trial, even though they were unaware of having done so. By contrast, patients with generalized anxiety disorder were completely unable to regulate emotional conflict and failed to engage the pregenual anterior cingulate in ways that would dampen amygdalar activity. Moreover, performance and brain activation were correlated with symptoms and could be used to accurately classify the two groups.

Conclusions

These data demonstrate that patients with generalized anxiety disorder show significant deficits in the noninstructed and spontaneous regulation of emotional processing. Conceptualization of anxiety as importantly involving abnormalities in emotion regulation, particularly a type occurring outside of awareness, may open up avenues for novel treatments, such as by targeting the medial prefrontal cortex.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 167 • Number 5 • May 2010
Pages: 545 - 554
PubMed: 20123913

History

Received: 4 July 2009
Accepted: 19 November 2009
Published online: 1 May 2010
Published in print: May 2010

Authors

Details

Amit Etkin, M.D., Ph.D.
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Katherine E. Prater, B.A.
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Fumiko Hoeft, M.D., Ph.D.
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Alan F. Schatzberg, M.D.
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Notes

Presented in part at the Human Brain Mapping annual conference, San Francisco, June 19, 2009. Received July 4, 2009; revisions received Sept. 6 and Oct. 29, 2009; accepted Nov. 19, 2009. From the Department of Psychiatry and Behavioral Sciences, the Center for Interdisciplinary Brain Science Research, and the Program in Neuroscience, Stanford University. Address correspondence and reprint requests to Dr. Etkin, Stanford University School of Medicine, 401 Quarry Rd., Stanford, CA 94305, [email protected] (e-mail).

Competing Interests

Dr. Etkin has served as a consultant for Neostim. Dr. Schatzberg has served as a consultant to BrainCells, CeNeRx, CNS Response, Corcept, Eli Lilly, Forest Labs, GlaxoSmithKline, Innapharma, Lundbeck, Merck, Neuronetics, Novartis, Pathway Diagnostics, Pfizer, PharmaNeuroBoost, Quintiles, Sanofi-Aventis, Synosis, Takeda, Xytis, and Wyeth and has received speaking fees from GlaxoSmithKline and Roche; he has equity holdings in BrainCells, CeNeRx, Corcept (co-founder), Forest, Merck, Neurocrine, Pfizer, PharmaNeuroBoost, Somaxon, and Synosis; and he was named an inventor on pharmacogenetic use patents on prediction of antidepressant response. The other authors report no financial relationships with commercial interests.

Funding Information

Supported by funds for a residency research program of the Veterans Affairs-Palo Alto Health Care System to Dr. Etkin, and NIH grants HD047520 and NS058899 to Dr. Menon and 5K23HD054720 to Dr. Hoeft.

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