What is the background of this study?

People with SAD (social anxiety disorder) fear being negatively evaluated in social settings. The characteristics of SAD include an onset during early adolescence, often a lifelong course and a great risk of comorbid disorders. While SAD has severe effects on one’s personal life and society, current treatment is not optimal. In order to improve interventions, the risk factors of developing SAD need to become more clear.

A patient with SAD fears acting in a way that will be humiliating or embarrassing in social situations. The behavioral and neurobiological correlates of that fear can be examined by using the Social Norm Processing Task. This task involves reading and evaluating stories describing (un)intentional violations of social norms. Studies using this Task found that people with social anxiety are more sensitive to unintentional violations of social norms. One study showed increased activation in the medial prefrontal cortex in the participants with SAD. In comparison to the control group, they also considered the stories more embarrassing and inappropriate, especially the story describing unintentional violations. Thus, social anxiety affects the embarrassment ratings for unintentional violations of social norms. Another study showed that participants with greater social anxiety levels rated the unintentional violations just as embarrassing as the intentional violations. Experiencing embarrassment underlies the development and maintenance of social anxiety.

However, no study examined whether the correlates of altered processing of unintentional social norm violations could be SAD endophenotypes. Endophenotypes are heritable and measurable components indicative of genetic vulnerability to disorders. These endophenotypes could improve our knowledge regarding the pathways leading to severe psychopathology, help identifying vulnerable individuals and improve the current intervention programs. Endophenotypes need to be related to the disorder, independent and already present in a preclinical state, heritable and they should cosegregate with the disorder in families of probands.

Hypothesis: brain activation and behavioral ratings are associated with processing unintentional violations of social norms.

Who participated and what materials were used?

Participants were recruited through the LFLSAD: Leiden Family Lab study on Social Anxiety Disorder (a multigenerational and multiplex family study). Eight families participated, including two generations of families carrying the gene linked to SAD. The inclusion of the families was based on the combination of a ‘proband’ parent (diagnosed with SAD) and a child who met criteria for SAD. Used were MRI scans and various measurements such as diagnostic interviews.

The Revised Social Norm Processing Task (R-SNPT) consisted of story reading, getting into the MRI scanner and rating the MRI scan. The stories described a neutral social situation and a situation in which a social norm was unintentionally or intentionally violated (baking a pie with friends: using the right amount of sugar, accidentally using salt, using salt as a prank). Participants had to imagine themselves in these social situations. After the MRI scan, they were asked to rate the stories’ inappropriateness and embarrassment.

What were the results?

No gender and age differences were observed between family members with and without SAD. Family members with SAD displayed higher levels of social anxiety.

Self-reported social anxiety was positively linked to brain activation in two brain clusters. One cluster was located in the occipital pole, the other in the frontal pole. No clusters showed negative associations with social anxiety. Heritability assessments suggest that brain activation in those clusters is heritable.

The R-SNPT ratings showed a significant relation between embarrassment and social anxiety, but none between inappropriateness and social anxiety. Follow-up analyses suggest positive associations between social anxiety and embarrassment regarding all three stories. Sensitivity analyses suggest that these findings were not driven by SAD. Embarrassment ratings in the intentional stories showed low heritability. Embarrassment scores for neutral and unintentional stories showed no heritability.

What is the conclusion of this study?

This study proves that brain activation associated with processing unintentional violations of social norms is a neurobiological candidate endophenotype of social anxiety disorder. These findings provide new insights in the neurological pathways leading to social anxiety disorder.