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Murray B. Stein, MD; Philippe R. Goldin, MS; Jitender Sareen, MD; Lisa T. Eyler Zorrilla, PhD; Gregory G. Brown, PhD

Arch Gen Psychiatry. 2002;59:1027-1034.

Background  Generalized social phobia (GSP) is characterized by fear of social interactions and sensitivity to disapproval by others. Given the established role of the amygdala as part of a distributed neural system for the processing of emotional cues, we hypothesized that subjects with GSP would exhibit greater amygdala activation in response to harsh (angry, fearful, and contemptous) vs accepting (happy) facial emotional expressions compared with healthy control subjects (HCs).

Methods  Fifteen subjects with DSM-IV GSP and 15 age-, sex-, handedness-, and education-matched HCs, free of psychotropic medication for at least 12 weeks, viewed 60 color photographs from a standardized set of human facial stimuli, during which the task was to identify the sex of the person in the photograph. Data were collected across 3 functional (echo-planar) runs using a Siemens 1.5-T magnet, and analyzed using Analysis of Functional Neuroimaging software (Medical College of Wisconsin, Milwaukee).

Results  In the left allocortex (including the amygdala, uncus, and parahippocampal gyrus), subjects with GSP produced a significantly greater percent blood oxygen level–dependent signal change than did HCs for contemptous compared with happy faces (GSP: 0.72% vs HC: -0.01%; F_1,29 = 9.56, P = .004, Cohen d = 1.15) and for angry compared with happy faces (GSP: 0.45% vs HC: -0.09%; F_1,29 = 6.78, P = .02, Cohen d = 1.00). Subjects with GSP and HCs did not produce a statistically different percent signal change for fearful or nonexpressive faces compared with the happy faces in this region.

Conclusions  These findings are consistent with a role for differential amygdala (and associated limbic) functioning in GSP. The pronounced response to contemptuous and angry facial expressions suggests that the amygdala in GSP may be particularly active in the processing of disorder-salient stimuli.

From the Department of Psychiatry, University of California–San Diego, and the Veterans Affairs San Diego Healthcare System, La Jolla, Calif. Dr Sareen is currently with the Department of Psychiatry, University of Manitoba, Winnipeg. Mr Goldin is currently with the Department of Psychology, Stanford University, Stanford, Calif. Dr Stein is a paid consultant to GlaxoSmithKline Co, Philadelphia, Pa.

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