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All living creatures have to cope with environmental
demands and threats that challenge their physical
or emotional homeostasis.

janna marie bas hoogendam

The Leiden Family Study on Social Anxiety Disorder: the search for neuroimaging endophenotypes

Imagine: you have to give an important presentation in front of an audience. You are the center of attention and all eyes are on you. How do you feel?

Or: you are invited to a party where you don’t know anyone. You enter the room and see that the other guests are already seated. What do you experience? Chances are you feel shy and uncomfortable in the beginning, tense maybe, but after a while these feelings will fade and you will have a good time. However, some people remain extremely nervous in social situations and even worry for days or weeks before a social event. These people have an intense fear of being negatively evaluated and are severely worried about doing something embarrassing in front of others. As a result, they try to avoid social situations as much as possible. This tendency could have a tremendous negative influence on their lives. They suffer from a psychiatric condition: Social Anxiety Disorder (SAD). 

The lifetime prevalence of SAD is around 10%. The effects of the disorder should not be underestimated: patients with SAD often experience problems at work, in activities with friends, and in their close relationships. In addition, patients with SAD have an above-average risk of suffering from alcohol addiction and mood disorders such as depression. This makes SAD a very disabling condition.


SAD often develops during late childhood and adolescence, when children are very sensitive to the opinion of others. Effective preventive interventions are important, and to develop them we need insight into the factors that make individuals vulnerable for developing SAD. Previous research has revealed that SAD has a genetic basis, but the genetic variations related to SAD are largely unknown, and, for several reasons, not easy to find. First of all, the disorder differs from one patient to another. In addition, it is assumed that multiple interacting genes play a role in the development of SAD. This complicates the search for a link between social anxiety and genes. However, new approaches and new study designs can help to unravel this connection.

In 2013, we started a large two-generation family study on SAD: the ‘Leiden Family Study on Social Anxiety Disorder (LFLSAD)‘. This family study is unique, in that we not only investigate patients with SAD, but also invite their partners and children to come to the lab, as well as the patients’ siblings and their partners and children. Within these families, we aim to determine so-called endophenotypes of SAD: characteristics that are genetically linked to the disorder and that make individuals vulnerable to developing SAD. Since endophenotypes are viewed as characteristics that are in between genes and behavior (in this case: social anxiety), they can facilitate the search for SAD-related genetic variations.

Nine families (132 family members in total) have participated in the LFLSAD. These families were characterized by a high prevalence of SAD, in both generations. Furthermore, (sub)clinical SAD was positively related to self‐reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. At present, we are exploring whether Magnetic Resonance Imaging (MRI) measures, both at the functional and structural level, could serve as endophenotypes of SAD. We investigate, for example, the behavioral and neural correlates of social norm processing, as a previous study of our group revealed that the level of social anxiety in the general population is related to increased levels of embarrassment in response to unintentional social norm violations. In addition, we explore whether gray matter characteristics are candidate endophenotypes of SAD. Results of these analyses are expected in the near future; feel free to This email address is being protected from spambots. You need JavaScript enabled to view it. or follow me on ResearchGate.

Figure was previously published in Bas-Hoogendam, J. M., Blackford, J. U., Brühl, A. B., Blair, K. S., van der Wee, N. J. A., & Westenberg, P. M. (2016). Neurobiological candidate endophenotypes of social anxiety disorder. Neuroscience & Biobehavioral Reviews, 71, 362–378. doi:10.1016/j.neubiorev.2016.08.040