There are three important strands to our work with patients with GSP and GAD. The first of these strands is determining the degree to which the pathology seen in GAD differs from that seen in GSP. In the first study of its kind, we presented patients with GSP, patients with GAD, patients with both GSP and GAD and no pathology individuals with angry, fearful, and neutral facial expression stimuli. We demonstrated clear differences in the pathology of GAD and GSP. Patients with GSP showed significantly increased activation to fearful relative to neutral expressions in several regions, including the amygdala. In contrast, patients with GAD showed significantly reduced activation to fearful relative to neutral faces compared to healthy individuals and patients with GSP but this was coupled with anomalously and significantly increased responses in a lateral region of prefrontal cortex. Patients with comorbid GAD/GSP appeared to present with the pathology associated with the GAD, but not the GSP. Our on-going work has continued to follow this approach. Specifically, we have been examining differences in automatic and controlled emotional regulation and, more recently, self-referential processing, across these patient groups. The second strand concerns the specific nature of the functional impairment seen in GSP. Patients with GSP show increased amygdala responses to socially threatening stimuli such as fearful and angry expressions. We followed this work up by examining the neural responses to receipt of praise or criticism in GSP. Participants were presented with positive, negative, and neutral statements (e.g., You are beautiful/ ugly/ human) that could be either about highly relevant and about themselves or less relevant about somebody else (e.g., He is beautiful). The results of this study indicated an important role for not only the amygdala but also medial prefrontal cortex (MPFC) in GSP. MPFC plays an important role in self-referential processing and it now appears that GSP reflects a particular sensitivity to self-referential information. Our on-going work has followed up on these results. In particular, we have been examining the specific nature of this sensitivity to self-referential information in patients with GSP. So, for example in one study we presented participants with the statements from the first study, however, this time the statements were always self-referential and what we varied instead was whether the statements originated from others (e.g., hearing You are beautiful/ ugly/ human) or the self (e.g., thinking I am beautiful/ ugly/ human). Whereas the healthy comparison individuals in this study showed significantly increased MPFC response to the I relative to U statements, the GSP patients showed increased MPFC responses to the U relative to the I comments. Further, the responses of the patients with GSP to the I statements correlated negatively with social anxiety symptom severity. These results underscore the importance of dysfunctional self-referential processing and MPFC in GSP. We believe that these data reflect a reorganization of self-referential reasoning in the disorder with a self-concept perhaps atypically related to the view of others. The third strand of work concerns the specific nature of the functional impairment seen in GAD. In particular, we have been examining whether some of the problems in emotional responding in GAD that we observed in our preliminary work with patients with this disorder might manifest in difficulties on decision making tasks. Using several decision making paradigms where successful performance is based on the appropriate representation of reward and punishment expectances, we observed significant impairment in patients with GAD (Devido et al., 2009). Notably, such impairments were not seen in patients with GSP. Our on-going work is following up these results and using functional magnetic resonance imaging to determine their neural basis.

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Blair, K S; Vythilingam, M; Crowe, S L et al. (2013) Cognitive control of attention is differentially affected in trauma-exposed individuals with and without post-traumatic stress disorder. Psychol Med 43:85-95
Blair, Karina S; Otero, Marcela; Teng, Cindy et al. (2013) Dissociable roles of ventromedial prefrontal cortex (vmPFC) and rostral anterior cingulate cortex (rACC) in value representation and optimistic bias. Neuroimage 78:103-10
Blair, Karina S; Geraci, Marilla; Smith, Bruce W et al. (2012) Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia, generalized anxiety disorder, and comorbid generalized social phobia/generalized anxiety disorder. Biol Psychiatry 72:476-82
Blair, Karina S; Geraci, Marilla; Korelitz, Katherine et al. (2011) The pathology of social phobia is independent of developmental changes in face processing. Am J Psychiatry 168:1202-9
Blair, Karina S; Geraci, Marilla; Otero, Marcela et al. (2011) Atypical modulation of medial prefrontal cortex to self-referential comments in generalized social phobia. Psychiatry Res 193:38-45
Blair, Karina S; Geraci, Marilla; Hollon, Nick et al. (2010) Social norm processing in adult social phobia: atypically increased ventromedial frontal cortex responsiveness to unintentional (embarrassing) transgressions. Am J Psychiatry 167:1526-32
DeVido, J; Jones, M; Geraci, M et al. (2009) Stimulus-reinforcement-based decision making and anxiety: impairment in generalized anxiety disorder (GAD) but not in generalized social phobia (GSP). Psychol Med 39:1153-61
Blair, Karina; Shaywitz, Jonathan; Smith, Bruce W et al. (2008) Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. Am J Psychiatry 165:1193-202