Specific anxiety disorders are characterized by altered emotion processing of phobia-specific stimuli at the neurobiological level. Recent work has concentrated on specific anxiety-provoking stimuli; focusing on arousal- or fear-related brain areas such as the amygdala. We analyzed brain activation during the cued anticipation of unpleasant or uncertain emotional stimuli as a means of modeling an unspecific anxiety-laden situation. Sixteen patients with social anxiety disorder (SAD) and eighteen healthy control subjects completed a task during functional magnetic resonance imaging involving the anticipation of cued visual stimuli with prior known emotional valence (positive, negative, and neutral) or prior unknown/ambiguous emotional content. The anticipated stimuli had no social phobia specific content. During the anticipation of emotional stimuli of prior known negative and prior ambiguous emotional valence, brain activity in patients with SAD was increased in the upper midbrain/dorsal thalamus, the amygdala, and in temporo-occipital and parietal regions as compared to control subjects. Activity was decreased in SAD in left orbitofrontal cortex. Activations in the amygdala and in occipital regions correlated with trait anxiety and social anxiety measures. In conclusion, SAD was associated with enhanced activation in brain regions involved in emotional arousal as well as in attention and perception processing during the anticipation of non-specific, general emotional stimuli. Hence, our results suggest that patients with SAD not only have an altered processing of specific feared stimuli, but also a more generally disturbed emotion processing in basic neural pathways. These findings have implications for diagnostic models and the treatment of SAD.
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