Amygdala and insula response to emotional images in patients with generalized social anxiety disorder

Amygdala and insula response to emotional images in patients with generalized social anxiety disorder


J Psychiatry Neurosci 2010; 34(4): 296-302

Sabin G. Shah, BS; Heide Klumpp, PhD; Mike Angstadt, BS; Pradeep J. Nathan, PhD; K. Luan Phan, MD

Shah, Klumpp, Angstadt, Phan — Department of Psychiatry, University of Michigan, Ann Arbor, Mich.; Nathan — Department of Psychiatry, University of Cambridge, UK; Phan — Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, Mich.


Background: Functional brain imaging studies have demonstrated amygdala and insula hyper-reactivity to probes of social threat in participants with generalized social anxiety disorder (gSAD). The amygdala and insula are known to serve broad functions in emotional processing, including integration of affective information. However, few studies have examined brain responses in socially anxious participants during general emotional processing. We examined brain response to emotionally evocative images in patients with gSAD and matched healthy controls.

Methods: Eleven patients with gSAD who were not taking psychotropic medications and did not have psychiatric comorbidities and 11 matched healthy controls underwent functional magnetic resonance imaging while viewing blocks of emotionally salient (positive, negative, neutral) pictures.

Results: Participants with gSAD exhibited enhanced bilateral amygdala and insula reactivity to negative (v. neutral) images compared with healthy controls who did not exhibit enhanced reactivity. Within the gSAD group, the extent of amygdala activation was correlated with social anxiety severity, whereas the extent of insula activation was correlated with trait anxiety.

Limitations: The small sample size may have limited our ability to detect group differences in other relevant brain regions and in behavioural measures.

Conclusions: In addition to prior findings of probes of social information processing, our findings suggest that the amygdala and insula responses are hyper-reactive to general emotional images with negative emotional content and that these brain regions may play divergent roles in their representation of different phenotypes.

Submitted Jul. 29, 2008; Revised Oct. 24, Dec. 18, 2008; Accepted Dec. 23, 2008

Acknowledgements: This research was supported by a Seed Grant from the Brain Research Foundation (K.L.P.) and an NIH grant MH076198 (K.L.P.). We thank Rose McCarron for her assistance in participant recruitment and study coordination.

Competing interests: None declared.

Contributors: Dr. Phan designed the study. Mr. Angstadt acquired the data, which all authors analyzed. Mr. Shah and Drs. Klumpp and Phan wrote the article, which Mrs. Angstadt and Shah and Drs. Nathan and Phan reviewed. All authors gave final approval for publication.

Correspondence to: Dr. K.L. Phan, Department of Psychiatry, University of Michigan, Rachel Upjohn Bldg., Room 2751, Box 6765, 4250 Plymouth Rd., Ann Arbor, MI 48109-2700; fax 734 936-7868;