Endophenotypes of Social Anxiety Disorder: Can We Detect Them and Are They Useful in Clinical Practice?

Social Anxiety Disorder

Social anxiety disorder (SAD) concerns an intense fear and avoidance of social situations and disturbance of general functioning (DSM IV, 1994). SAD patients show a high rate of impairment of social functioning, working- and family-life and close relationships. In addition, SAD is correlated with psychiatric comorbidity. More insight in the development of the disorder is essential to develop preventive interventions for the disorder.

Earlier studies showed that SAD runs in families. This suggests a potential role of genetics as well as shared family environment in the development of SAD. However, it remains unclear which genes are specifically involved in SAD.

Endophenotype approach

Profiling endophenotypes of social anxiety disorder (SAD) will advance our understanding of the genetic architecture of this disorder. Endophenotypes are genetic trait markers, linking a phenotype to a genotype. For a marker to be considered an endophenotype, “it has to (1) be associated with the phenotype (formal diagnosis), (2) be independent of clinical state, (3) be highly heritable, and (4) the impairment must co-segregate with the illness within a family, with non-affected family members showing impairment relative to the general population” (Glahn, Thompson, & Blangero, 2007).

Some studies have directly tested whether candidate endophenotypes meet the criteria for endophenotypes for other forms of psychopathology, such as depression and schizophrenia. For SAD, the support for endophenotypes is mostly indirect, as they have rarely been studied with the proper research designs, specifically multigenerational family designs.

The Leiden Family Study on Social Anxiety Disorder

Currently, researchers of Leiden University and the Leiden University Medical Center (LUMC) are performing a unique family study with a 3-generation genetic design to detect endophenotypes of SAD in extended families (https://www.leidenfamilylab.nl). In this study, an affected individual with SAD, his or her siblings and children are tested, as well as the partners of each family member. The key question addressed in this project is whether the psychophysiological and neurocognitive abnormalities often reported in SAD patients are heritable, and can thus be found in family members of SAD patients as well. This family project is, to the best of our knowledge, the first comprehensive study aiming to determine endophenotypes of SAD (https://www.facebook.com/FamilieOnderzoekExtremeVerlegenheid).

Lorentz Center Workshop

Building on the Leiden Family Study, this Lorentz Center workshop aims to gain more insight into candidate endophenotypes of SAD and their potential relevance for clinical practice. We will look into genetic approaches to social anxiety and other psychiatric disorders, discuss candidate endophenotypes of SAD and consider the clinical implications of the findings. In addition, the first results from the Leiden Family Study will be discussed. The output of the workshop-days will be published as a position paper that sets out the research agenda for the field of endophenotypes for SAD. Furthermore, the workshop aims to bring together participants from different traditions and backgrounds, in order to establish longer-lasting collaborations and to facilitate collaborations on papers and cross-site grant applications.