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.

The functional 5-HT1A receptor polymorphism affects response inhibition processes in a context-dependent manner.

Cognitive control processes may depend on contextual information, sometimes improving performance, but impairing performance if expectancies about forthcoming events induce pre-potent responses. The neurobiological bases of these effects are not understood. Here, we examine context-dependent variations of response control processes using the AX-CPT task with respect to the relevance of the functional serotonin 1A receptor polymorphism (5-HT1A C(-1019)G) in a sample of healthy subjects (N=90) by means of event-related potentials (ERPs). The results show that, when context information is helpful to drive behavioural performance, carriers of the -1019G allele reveal compromised cognitive control. Yet, they show enhanced task performance when strong context representations would lead to declines in behavioural control. These findings are paralleled by modulations of the (Nogo)-P3 ERP-component. These results show for the first time that, even though the -1019G allele enhances the risk to develop anxiety disorders, it also confers an advantage to its carriers in terms of better cognitive control processes in conditions where contextual information compromises cognitive control. Effects of the 5-HT1A C(-1019)G polymorphism were further modulated by anxiety sensitivity. As the functional effect of the 5-HT1A C(-1019)G polymorphism has previously been shown to be rather specific for serotonergic 1A autoreceptors in the dorsal raphe nucleus (DRN), the results suggest that contextual modulations in cognitive control may be exerted by the DRN.