مدولاسیون غیر معمولی از قشر جلو مغزی میانی برای نظرات خودارجاعی در هراس اجتماعی عمومی

Generalized social phobia (GSP) involves the fear of being negatively evaluated. Previous work suggests that self-referentiality, mediated by the medial prefrontal cortex (MFPC), plays an important role in the disorder. However, it is not clear whether this anomalous MPFC response to self-related information in patients with GSP concerns an increased representation of their own or others' opinions. In this article, we examine whether GSP is associated with increased response to own (1st person) or other individuals' (2nd person) opinions relative to healthy individuals. Unmedicated individuals with GSP (n = 15) and age-, IQ-, and gender-matched comparison individuals (n = 15) read 1st (e.g., I'm ugly), and 2nd (e.g., You're ugly) person viewpoint comments during functional magnetic resonance imaging. We observed significant group-by-viewpoint interactions within the ventral MPFC. Whereas the healthy comparison individuals showed significantly increased (or less decreased) BOLD responses to 1st relative to 2nd person viewpoints, the patients showed significantly increased responses to 2nd relative to 1st person viewpoints. The reduced BOLD responses to 1st person viewpoint comments shown by the patients correlated significantly with severity of 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.

Generalized social phobia (GSP) involves a strong and persistent fear of social or performance situations that have the potential for negative evaluation. It is a relatively common disorder associated with a high risk for alcohol and drug abuse, depression, and suicide (Kaufman and Charney, 2000, Kessler, 2003 and Beesdo et al., 2007). Functional magnetic resonance imaging (fMRI) studies in GSP have focused on examining responses to social stimuli. In particular, extensive work has examined the response to facial expressions, including harsh (Phan et al., 2006), angry (Stein et al., 2002, Straube et al., 2004, Straube et al., 2005 and Blair et al., submitted for publication), fearful (Stein et al., 2002, Blair et al., 2008b and Blair et al., submitted for publication), disgusted (Amir et al., 2005), happy (Straube et al., 2005) and neutral (Birbaumer et al., 1998 and Stein et al., 2002) expressions. This work finds increased amygdala response in GSP (Stein et al., 2002, Straube et al., 2005 and Phan et al., 2006), though the dorsal medial prefrontal cortex (MPFC) has also been implicated (Stein et al., 2002, Straube et al., 2004, Amir et al., 2005 and Blair et al., 2008b). However, the response to facial expressions in both healthy individuals (Pessoa et al., 2002, Pessoa et al., 2005 and Mitchell et al., 2007) and patients (Pine et al., 2005 and McClure et al., 2007) is under considerable attentional control; increased attention to other features in the environment reduces the representation of facial expressions and thus the emotional response to them (Pessoa and Ungerleider, 2004, Mitchell et al., 2007 and Luo et al., 2010). Moreover, the intent and self-relevance of facial expressions can be difficult to ascertain (i.e., “Are you laughing at me or smiling with me? Angry with me or somebody else?”). Given that fears of other people's scrutiny and judgment lie at the core of GSP (First et al., 1995), aberrant processing of self-referential information may play a role in the disorder. In the first study to directly examine self-referential processing in GSP using fMRI, patients were assessed when processing self- vs. other-referential criticism (e.g., “You're ugly” vs. “He's ugly”) and praise (e.g., “You're beautiful” vs. “He's beautiful”) ( Blair et al., 2008a). This study revealed selectively increased BOLD responses within both the amygdala and the dorsal MPFC in patients with GSP to self-referential criticism. In short, these data indicated that the heightened sensitivity to self-referential criticism in patients with GSP reflects dysfunction in the dorsal MPFC as well as the amygdala (see also recent work by Goldin and colleagues that examines emotion regulation in social phobia to criticism [ Goldin and Manber-Ball, 2009 and Goldin and Gross, 2010]). The MPFC finding is of particular relevance given the extensive data implicating dorsal as well as ventral MPFC in self-referential processing ( Johnson et al., 2002, Fossati et al., 2003, Phan et al., 2004, Seger et al., 2004, Mitchell et al., 2005 and Moran et al., 2006; for review see Gillihan and Farah, 2005, Northoff et al., 2006, Schmitz and Johnson, 2007, Legrand and Ruby, 2009 and van der Meer et al., 2010). Specifically, both regions show increased responses during self-related as opposed to non-self-related reasoning. Moreover, in addition to the MPFC, recent work has also highlighted the role of the amygdala in the response to praise and criticism in healthy individuals ( Frewen et al., 2010). Taken together, these findings suggest that the MPFC might make independent contributions to GSP but may also interact as part of a circuit. The goal of the current study was to extend our earlier work (Blair et al., 2008a) and to specifically examine whether patients with GSP show aberrant responding to self-referential comments depending on whether the origin of those comments is another individual (e.g., hearing “You're ugly”) or the self (e.g., thinking “I'm ugly”). Our aim is to go beyond describing the regions implicated in GSP and rather to probe the nature of information-processing perturbations that occur within these regions. Without this information, it will be difficult to optimize treatments for this disorder, particularly when they are targeted towards specific cognitive processes. As such, we used a novel verbal-comment paradigm to implement a 2(Viewpoint: 1st or 2nd Person) by 3(Valence: negative, neutral and positive) by 2(Group: GSP, healthy comparison) design. On the basis of our earlier data, which found these stimuli to elicit GSP-related perturbations in dorsal and ventral MPFC (Blair et al., 2008a and Blair et al., 2010), we hypothesize that GSP involves hyper-responsiveness to social feedback from others. Thus, we expect patients with GSP to show (to 2nd person point-of-view comments) increased responses within MPFC (i.e., there will be a group-by-viewpoint interaction). This might be particularly marked for others' criticism (i.e., there will be a group-by-viewpoint-by-valence interaction). Alternatively, given that GSP is associated with an increased level of self-criticism (Cox et al., 2002 and Cox et al., 2004), it could be hypothesized that it involves hyper-responsiveness to self-referential comments whether these are generated internally or externally (i.e., there will be a main effect of group within the MPFC).