Atypical Modulation of Medial Prefrontal Cortex to Self-referential Comments in Generalized Social Phobia

Overview

Journal Psychiatry Res

Specialty Psychiatry

Date 2011 May 24

PMID 21601433

Citations 34

Authors

Karina S Blair

Marilla Geraci

Marcela Otero

Catherine Majestic

Stephanie Odenheimer

Madeline Jacobs

R J R Blair

Daniel S Pine

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Increased default mode network activation in depression and social anxiety during upward social comparison.

Acuna A, Acuna A, Morales S, Morales S, Uriarte-Gaspari L, Uriarte-Gaspari L Soc Cogn Affect Neurosci. 2025; 20(1).

PMID: 39882939 PMC: 11792650. DOI: 10.1093/scan/nsaf012.

A brain model of altered self-appraisal in social anxiety disorder.

Jamieson A, Harrison B, Delahoy R, Schmaal L, Felmingham K, Phillips L Transl Psychiatry. 2023; 13(1):344.

PMID: 37951951 PMC: 10640593. DOI: 10.1038/s41398-023-02644-7.

Neurocognitive Model of Schema-Congruent and -Incongruent Learning in Clinical Disorders: Application to Social Anxiety and Beyond.

Moscovitch D, Moscovitch M, Sheldon S Perspect Psychol Sci. 2023; 18(6):1412-1435.

PMID: 36795637 PMC: 10623626. DOI: 10.1177/17456916221141351.

Psychosocial stress and cannabinoid drugs affect acetylation of α-tubulin (K40) and gene expression in the prefrontal cortex of adult mice.

Tomas-Roig J, Ramasamy S, Zbarsky D, Havemann-Reinecke U, Hoyer-Fender S PLoS One. 2022; 17(9):e0274352.

PMID: 36129937 PMC: 9491557. DOI: 10.1371/journal.pone.0274352.

Neural correlates of attentional control in social anxiety disorder: the impact of early-life adversity and DNA methylation.

Wiegand A, Munk M, Drohm S, Fallgatter A, MacIsaac J, Kobor M J Psychiatry Neurosci. 2021; 46(6):E663-E674.

PMID: 34916236 PMC: 8687622. DOI: 10.1503/jpn.210064.

References

Lemogne C, le Bastard G, Mayberg H, Volle E, Bergouignan L, Lehericy S . In search of the depressive self: extended medial prefrontal network during self-referential processing in major depression. Soc Cogn Affect Neurosci. 2009; 4(3):305-12. PMC: 2728628. DOI: 10.1093/scan/nsp008. View

Beesdo K, Bittner A, Pine D, Stein M, Hofler M, Lieb R . Incidence of social anxiety disorder and the consistent risk for secondary depression in the first three decades of life. Arch Gen Psychiatry. 2007; 64(8):903-12. DOI: 10.1001/archpsyc.64.8.903. View

Johnson S, Baxter L, Wilder L, Pipe J, Heiserman J, Prigatano G . Neural correlates of self-reflection. Brain. 2002; 125(Pt 8):1808-14. DOI: 10.1093/brain/awf181. View

Kaufman J, Charney D . Comorbidity of mood and anxiety disorders. Depress Anxiety. 2000; 12 Suppl 1:69-76. DOI: 10.1002/1520-6394(2000)12:1+<69::AID-DA9>3.0.CO;2-K. View

Fossati P, Hevenor S, Graham S, Grady C, Keightley M, Craik F . In search of the emotional self: an fMRI study using positive and negative emotional words. Am J Psychiatry. 2003; 160(11):1938-45. DOI: 10.1176/appi.ajp.160.11.1938. View

Schmitz T, Johnson S . Relevance to self: A brief review and framework of neural systems underlying appraisal. Neurosci Biobehav Rev. 2007; 31(4):585-96. PMC: 1973156. DOI: 10.1016/j.neubiorev.2006.12.003. View

Pessoa L, Padmala S, Morland T . Fate of unattended fearful faces in the amygdala is determined by both attentional resources and cognitive modulation. Neuroimage. 2005; 28(1):249-55. PMC: 2427145. DOI: 10.1016/j.neuroimage.2005.05.048. View

Yoshimura S, Okamoto Y, Onoda K, Matsunaga M, Ueda K, Suzuki S . Rostral anterior cingulate cortex activity mediates the relationship between the depressive symptoms and the medial prefrontal cortex activity. J Affect Disord. 2009; 122(1-2):76-85. DOI: 10.1016/j.jad.2009.06.017. View

Cox B, Fleet C, Stein M . Self-criticism and social phobia in the US national comorbidity survey. J Affect Disord. 2004; 82(2):227-34. DOI: 10.1016/j.jad.2003.12.012. View

10.

Seger C, Stone M, Keenan J . Cortical Activations during judgments about the self and an other person. Neuropsychologia. 2004; 42(9):1168-77. DOI: 10.1016/j.neuropsychologia.2004.02.003. View

11.

Rapee R, Heimberg R . A cognitive-behavioral model of anxiety in social phobia. Behav Res Ther. 1997; 35(8):741-56. DOI: 10.1016/s0005-7967(97)00022-3. View

12.

Kessler R . The impairments caused by social phobia in the general population: implications for intervention. Acta Psychiatr Scand Suppl. 2003; (417):19-27. DOI: 10.1034/j.1600-0447.108.s417.2.x. View

13.

Mitchell J, Neil Macrae C, Banaji M . Dissociable medial prefrontal contributions to judgments of similar and dissimilar others. Neuron. 2006; 50(4):655-63. DOI: 10.1016/j.neuron.2006.03.040. View

14.

Legrand D, Ruby P . What is self-specific? Theoretical investigation and critical review of neuroimaging results. Psychol Rev. 2009; 116(1):252-82. DOI: 10.1037/a0014172. View

15.

Alden L, Wallace S . Social phobia and social appraisal in successful and unsuccessful social interactions. Behav Res Ther. 1995; 33(5):497-505. DOI: 10.1016/0005-7967(94)00088-2. View

16.

Gillihan S, Farah M . Is self special? A critical review of evidence from experimental psychology and cognitive neuroscience. Psychol Bull. 2005; 131(1):76-97. DOI: 10.1037/0033-2909.131.1.76. View

17.

van der Meer L, Costafreda S, Aleman A, David A . Self-reflection and the brain: a theoretical review and meta-analysis of neuroimaging studies with implications for schizophrenia. Neurosci Biobehav Rev. 2009; 34(6):935-46. DOI: 10.1016/j.neubiorev.2009.12.004. View

18.

Straube T, Mentzel H, Miltner W . Common and distinct brain activation to threat and safety signals in social phobia. Neuropsychobiology. 2005; 52(3):163-8. DOI: 10.1159/000087987. View

19.

Blair K, Geraci M, DeVido J, McCaffrey D, Chen G, Vythilingam M . Neural response to self- and other referential praise and criticism in generalized social phobia. Arch Gen Psychiatry. 2008; 65(10):1176-84. PMC: 2785901. DOI: 10.1001/archpsyc.65.10.1176. View

20.

Moran J, Heatherton T, Kelley W . Modulation of cortical midline structures by implicit and explicit self-relevance evaluation. Soc Neurosci. 2009; 4(3):197-211. PMC: 4532268. DOI: 10.1080/17470910802250519. View