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Genetic predisposition to social anxiety disorder measurable in the brain

It was already known that social anxiety disorder often affects more than one person in the same family. But research by PhD student Janna Marie Bas-Hoogendam has now shown that there are genetic brain characteristics that are associated with social anxiety. The PhD ceremony will take place on 14 January.

In layperson’s terms, social anxiety disorder (SAD) is extreme shyness. Almost all of us feel shy at some point in our lives: if we have to give a presentation in front of an audience or attend a job interview, for example. We call it nerves, but that the underlying is a fear of slipping up and being judged by others. 


Around 10% of the population suffers from social anxiety to such an extent, and in so many situations, that people withdraw from social situations. They try to avoid contact with others so as to prevent people from developing critical or negative thoughts about them. ‘A woman might go shopping in another village because she is afraid of bumping into someone she knows,’ says neuroscientist Janna Bas-Hoogendam. ‘Or a man might refuse a promotion at work because he would then have to communicate with more people.’

Genetic vulnerability

Bas-Hoogendam, who works at the Department of Developmental and Educational Psychology and the Department of Psychiatry at the LUMC, reviewed the existing literature on SAD. It has been known for some time that SAD often affects multiple family members. This suggests genetic vulnerability, which is precisely what Bas-Hoogendam and her colleagues investigated. She invited parents with SAD who had at least one child with the same disorder to take part in her research together with other family members. This ‘Leiden Family Study into SAD’ was conducted as part of the Health, Prevention and the Human Lifecycle profile. After a long search, Bas-Hoogendam found nine ‘extremely shy’ families, comprising 132 people in total. She used MRI scans of the brains of 110 family members to look for characteristics that are both related to SAD and heritable. 

Janna Marie Bas-Hoogendam

More grey matter

Bas-Hoogendam began by looking at the structure of the family members’ brains. She noticed that family members with more SAD symptoms have more grey matter in the dorsal striatum, an area deep in the brain. She also discovered abnormalities in the thickness and surface area of other regions of the brain, and found that these brain characteristics are partly hereditary. However, not all family members with a genetic vulnerability to SAD will actually go on to develop it. Why that is or what triggers  SAD  is unclear. ‘We think that it involves a complex interaction between innate characteristics and environmental factors,’ says Bas-Hoogendam.

Other processes

Bas-Hoogendam also discovered a positive association between the intensity of SAD symptoms and activity in the subcortical and cortical regions of the brain. She presented the test subjects with images of the same neutral faces on several occasions. People without SAD reacted to them less and less: they had made their judgment (‘no danger’) and lost interest after having seen the same faces several times. However, people with SAD continued to react equally strongly, as if they were seeing the face for the first time.

Intentional or unintentional

Another aspect of the research involved measuring brain activity when transgressing a social norm, either intentionally or unintentionally. The test subjects were told three different versions of a very short story about them and a woman lying on the beach: in the first version, they were told that they walked around the woman; in the second version, they tripped over her legs; and in the third version, they deliberately kicked the woman in the leg. Bas-Hoogendam compared the brain activity in response to the intended and unintended transgression of social norms, and found that the stories with the unintended transgression in particular led to increased brain activity in the participants with SAD symptoms. ‘They are extremely afraid of making mistakes in the company of others, and you can see that in their brains.’ Bas-Hoogendam concludes that people with SAD have an overactive and emotional brain, and that their anxiety prevents them from living life to the full.

Treatment possible

On a positive note, it is possible to treat both the disorder and genetic vulnerability to it. We now know that the brain is capable of making new connections. This means that treatment can minimise feelings of anxiety through treatment and reduce the associated avoidance behaviour, possibly with the aid of medication. ‘It’s not easy,’ says Bas-Hoogendam, ‘but it can be done.’

PhD defence ‘Extremely Shy & Genetically Close'
Janna Marie Bas-Hoogendam
Thursday 14 January 2020, 15.00-15.45

Text: Corine Hendriks
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