Of 'disgrace' and 'pain'--corticolimbic interaction patterns for disorder-relevant and emotional words in social phobia.

Limbic hyperactivation and an impaired functional interplay between the amygdala and the prefrontal cortex are discussed to go along with, or even cause, pathological anxiety. Within the multi-faceted group of anxiety disorders, the highly prevalent social phobia (SP) is characterized by excessive fear of being negatively evaluated. Although there is widespread evidence for amygdala hypersensitivity to emotional faces in SP, verbal material has rarely been used in imaging studies, in particular with an eye on disorder-specificity. Using functional magnetic resonance imaging (fMRI) and a block design consisting of (1) overall negative, (2) social-phobia related, (3) positive, and (4) neutral words, we studied 25 female patients with social phobia and 25 healthy female control subjects (HC). Results demonstrated amygdala hyperactivation to disorder-relevant but not to generally negative words in SP patients, with a positive correlation to symptom severity. A functional connectivity analysis revealed a weaker coupling between the amygdala and the left middle frontal gyrus in patients. Symptom severity was negatively related to connectivity strength between the amygdala and the ventromedial prefrontal and orbitofrontal cortex (Brodmann Area 10 and 11). The findings clearly support the view of a hypersensitive threat-detection system, combined with disorder-related alterations in amygdala-prefrontal cortex connectivity in pathological anxiety

Correlations between the clinical measures and the behavioral rating data for negative, SP-related, positive, and neutral words within the group of social phobia patients (Pearson's correlation/p-value (2-tailed)).

<p>SPS, Social Phobia Scale; SIAS, Social Interaction Anxiety Scale; BDI, Beck Depression Inventory; STAI-T, State-Trait Anxiety Inventory, Trait version; STAI-S, State-Trait Anxiety Inventory, State version. Significant correlations are displayed in bold letters.</p><p>Correlations between the clinical measures and the behavioral rating data for negative, SP-related, positive, and neutral words within the group of social phobia patients (Pearson's correlation/p-value (2-tailed)).</p

Correlations with disorder severity.

<p><b>a</b>) Left: Association of the patients' SPS-scores with right amygdala responsiveness to SP-related versus negative words, rendered on an anatomical template in MNI-space. Color bar, correlation coefficient <i>r</i>. Right: Scatter plot depicting the positive correlation of the mean cluster activation values (left panel) and the SPS-scores. <b>b</b>) Left: Association of the patients' SPS-scores and the functional connectivity between the left amygdala and the right BA 10 and 11, rendered on an anatomical template in MNI-space. Color bar, correlation coefficient −<i>r</i>. Right: Scatter plot depicting the negative correlation of the mean cluster activation values (left panel) and the SPS-scores.</p

Significant results for post-hoc comparisons of the significant word-category x group interaction effect in the amygdala, conducted at p = 0.005 uncorrected, representing a Bonferroni-corrected 0.05 probability.

<p>Coordinates are given in MNI space.</p><p>SP, Social Phobia patients; HC, healthy controls.</p><p>Significant results for post-hoc comparisons of the significant word-category x group interaction effect in the amygdala, conducted at p = 0.005 uncorrected, representing a Bonferroni-corrected 0.05 probability.</p

Region of interest analysis of the amygdala.

<p>Left: bar graphs depicting the mean contrast value for negative, SP-related, and positive versus neutral words extracted from x = −18, y = 0, z = −24. Error bars, SEM. Right: coronal view (y = 0), depicting the significant group x word category interaction in the bilateral amygdala.</p

Mean differences for patients with social phobia (SP) and healthy controls (HC) concerning age, verbal intelligence, depression (BDI), Trait- and State anxiety (STAI-T and STAI-S) and social phobia symptoms (SPS/SIAS).

<p><i>M</i> =  Mean; SD  =  standard deviation. BDI, Beck Depression Inventory; STAI-T, State-Trait Anxiety Inventory, Trait version; STAI-S, State-Trait Anxiety Inventory, State version; SPS, Social Phobia Scale; SIAS, Social Interaction Anxiety Scale.</p>a<p>Assessed with the Mehrfachwahl-Wortschatz-Intelligenztest <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109949#pone.0109949-Lehrl1" target="_blank">[47]</a>.</p><p>Mean differences for patients with social phobia (SP) and healthy controls (HC) concerning age, verbal intelligence, depression (BDI), Trait- and State anxiety (STAI-T and STAI-S) and social phobia symptoms (SPS/SIAS).</p