Social anxiety disorder (SAD) is a disabling psychiatric disorder characterised by an excessive fear and avoidance of social situations. About 10 – 15% of individuals will develop SAD over the life-course, and while treatments such as cognitive behavioural therapy are effective for some, symptoms are often chronic and unremitting.
Despite a pressing need, the biological markers of SAD remain largely unknown. In response to this, an international team of researchers, led by Janna Marie Bas-Hoogendam from Leiden University with co-author Dr. Annette Bruhl of the Department of Psychiatry, reviewed the evidence of genetic and neurobiological markers of social anxiety vulnerability.
Evidence from family and twin studies indicates moderate heritability of SAD from one generation to the next. However, determining the individual genes underlying SAD is a colossal effort, and examination of “endophenotypes” can make this endeavour more tractable. Endophenotypes are heritable characteristics linked to a disease, traditionally defined by four criteria: (1) association with the disorder, (2) being a stable trait, even in a preclinical state, (3) heritability and (4) co-segregation within a family, where relatives of the affected family member show altered levels of the endophenotype relative to the population.
The authors underscore the importance of endophenotypes in the study of SAD, suggesting that they could lead to the discovery of mechanisms that make children of parents with SAD vulnerable to develop the disorder themselves. Examination of endophenotypes could also advance prevention efforts and treatments that are targeted at these genetic vulnerabilities.
Their findings, recently published in Neuroscience and Biobehavioral Reviews, identify four potential neuroimaging endophenotypes of SAD. These include activity of the amygdala and medial prefrontal cortex, whole-brain functional connectivity and morphological changes. Candidate endophenotypes were evaluated based on the criteria outlined above. While the strongest evidence upholds the primary criterion (i.e., an association between the endophenotype and SAD) across these candidate endophenotypes, preliminary support for the remaining criteria warrants further investigation. For example, data suggest that amygdala function and functional connectivity meets the first three endophenotype criteria, yet further research of familial co-segregation is necessary.
In light of these results, the researchers suggest that longitudinal, multi-generation family-studies of individuals with SAD and their relatives will be key in unraveling the mechanisms that lead to social anxiety.
We spoke with Dr. Bas-Hoogendam about the significance of her findings, as well as future directions:
“[Our] results are promising, but more research, preferably in families enriched for SAD, is needed to establish whether these measures are reliable SAD-endophenotypes. To the best of our knowledge, the Leiden Family Study on Social Anxiety Disorder is the first study specifically aimed to discover these endophenotypes, using a family-design involving two generations. In this study, neuroimaging data were collected from 9 families containing multiple family members with social anxiety (total n=114). More information about this study can be found at the Open Science Framework website, and it’s our hope that this study could contribute to unravelling the pathways to social anxiety.”
Written by Maggie Westwater
Cover Image: ‘DNA’ by MIKI Yoshihito licensed under CC BY-ND-NC 2.0