Atypical modulation of medial prefrontal cortex to self-referential comments in generalized social phobia

Karina S. Blair, Marilla Geraci, Marcela Otero, Catherine Majestic, Stephanie Odenheimer, Madeline Jacobs, R. J.R. Blair, Daniel S. Pine

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)38-45
Number of pages8
JournalPsychiatry Research - Neuroimaging
Issue number1
StatePublished - Jul 30 2011
Externally publishedYes


  • Amygdala
  • FMRI
  • Medial prefrontal cortex
  • Self-referentiality
  • Social phobia

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Psychiatry and Mental health


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