Social anxiety disorder (SAD) is characterized by exaggerated amygdala reactivity in response to symptom provocation, but it is unclear if such hyper-reactivity is elicited by disorder-specific challenges only or characterizes reactions to aversive stimuli in general. Here, using functional magnetic resonance imaging in 14 patients with SAD, as compared to 12 healthy controls, we found that amygdala hyper-reactivity is confined to disorder-relevant social stimulation. SAD patients displayed increased amygdala reactivity to fearful as compared to neutral facial pictures, but not in response to generally aversive but mainly non-social stimulation when compared to neutral pictorial stimuli taken from the International Affective Picture System. The increased amygdala reactivity was not mediated by an altered prefrontal inhibition among SAD patients as compared to controls, suggesting increased bottom-up processes rather than attenuated top-down control. In conclusion, the enhanced amygdala reactivity in SAD seems specific to socially relevant stimuli rather than aversive stimuli in general.

We aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive-behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential bio-marker for SAD treatment selection.

Animal studies indicate that substance P (SP) and its preferred neurokinin-1 (NK1) receptor modulate stress and anxiety-related behavior. Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion. Exploring this relation could provide important insights into the neurobiological underpinnings of human anxiety and the etiology of anxiety disorders, as anxious traits are associated with increased susceptibility to develop psychopathological conditions. Here we examined the relationship between central NK1 receptor availability and selfrated measures of trait anxiety, neuroticism, and extraversion. The amygdala was chosen as the primary region of interest since this structure has been suggested to mediate the effect of the SP-NK1 system on anxiety. Anxious traits and NK1 receptor availability, determined with positron emission tomography and the radiotracer [C-11]GR205171, were measured in 17 healthy individuals. Voxel-wise analyses showed a significant positive correlation between bilateral amygdala NK1 receptor availability and trait anxiety, and a trend in similar direction was observed for neuroticism. Conversely, extraversion was found to be negatively associated with amygdala NK1 receptor availability. Extraversion also correlated negatively with the NK1 measure in the cuneus/precuneus and fusiform gyrus according to exploratory whole-brain analyses. In conclusion, our findings indicate that amygdala NK1 receptor availability is associated with anxiety-related personality traits in healthy subjects, consistent with a modulatory role for the SP-NK1 system in human anxiety.