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Genetics Play a Role in Social Anxiety Disorder, Study Finds

The serotonin transporter gene “SLC6A4” is linked to social anxiety disorder.

Source: Petrol/CanStockPhoto

Researchers at the Institute of Human Genetics at the University of Bonn in Germany recently discovered that a specific serotonin transporter gene called “SLC6A4” is strongly correlated with someone's odds of suffering from social anxiety disorder (SAD). The initial findings of this research were published online ahead of print March 9 in the journal Psychiatric Genetics.

Social anxiety disorder (or social phobia) is a common and heritable psychiatric disorder that is driven by a combination of genetic and environmental factors. Until now, genetic studies on SAD have been rare. According to the researchers, "This is the largest association study so far into social phobia."

For this study, the German researchers genotyped 321 patients with SAD and 804 controls without social phobia. Then, they carried out a single-marker analysis to identify a quantitative association between SAD and avoidance behaviors. Their results provide evidence that the serotonin transporter gene SLC6A4 is frequently correlated with anxiety-related traits.

Notably, selective-serotonin reuptake inhibitors (SSRIs) are often prescribed to treat depression and anxiety disorders. SSRIs are believed to target the serotonin transporter gene SLC6A4.

People with social anxiety tend to avoid larger groups and situations in which they fear being judged by others. SAD is marked by symptoms such as increased heart rate, sweaty palms, shakiness, shortness of breath, etc.

The physiological discomfort of social anxiety reinforces avoidance behaviors and a withdrawal from face-to-face social contact. The fear of social encounters can lead to isolation and loneliness that snowballs. Unfortunately, people with social anxiety who rely excessively on social media to maintain a sense of connectedness may actually exacerbate their feelings of perceived social isolation, according to a recent study by researchers at the University of Pittsburgh School of Medicine.

Serotonin Is Complicated: Too Much Serotonin Linked to Social Anxiety Disorder

In 1948, when Maurice M. Rapport first isolated the chemical serotonin (5-hydroxytryptamine, 5-HT) in the human body and brain, serotonin was initially classified as a “serum agent that affected vascular tone.” Today, serotonin is commonly viewed as a neurotransmitter that helps to maintain mood balance.

Although there is a strong link between serotonin, depression, and social anxiety disorders; scientists remain uncertain about which comes first in terms of driving the correlation vs. causation dynamic between serotonin and psychiatric disorders. For example: Do low levels of serotonin contribute to social anxiety or does social phobia trigger a decrease in serotonin levels?

Interestingly, a 2015 study, "Serotonin Synthesis and Reuptake in Social Anxiety Disorder,“ published in JAMA Psychiatry reported that Individuals with social phobia have too much serotonin—not too little.

Surprisingly, the researchers found that the more serotonin someone with SAD self-produced, the more anxious he or she became in social situations. This raises doubt about the common assumption that selective serotonin reuptake inhibitor (SSRIs) help to lower social anxiety by keeping more serotonin in circulation.

In a statement, co-author Andreas Frick, a doctoral student at Uppsala University Department of Psychology said,

"Not only did individuals with social phobia make more serotonin than people without such a disorder, they also pump back more serotonin. We were able to show this in another group of patients using a different tracer which itself measures the pump mechanism.

We believe that this is an attempt to compensate for the excess serotonin active in transmitting signals. Serotonin can increase anxiety and not decrease it as was previously often assumed."

Taken together, all of this new research marks a significant leap forward when it comes to identifying changes in the brain's chemical messengers in people who suffer from social anxiety disorders. That said, much more research is needed to fully understand the enigmatic and complex workings of serotonin and transporter gene SLC6A4.

"There is still a great deal to be done in terms of researching the genetic causes of this illness," Andreas Forstner from the Institute of Human Genetics at the University of Bonn concluded.

If you would like to get involved in the genetic research on social anxiety disorder, Forstner and colleagues are encouraging the general public to participate in their research online by visiting their website: Social Phobia Research. The more people that get involved in the study of social anxiety disorder, serotonin, and SLC6A4, the more precisely the researchers will be able to decode these complex mechanisms.


Andreas J. Forstner, Stefanie Rambau, Nina Friedrich, Kerstin U. Ludwig, Anne C. Böhmer, Elisabeth Mangold, Anna Maaser, Timo Hess, Alexandra Kleiman, Antje Bittner, Markus M. Nöthen, Jessica Becker, Franziska Geiser, Johannes Schumacher, Rupert Conrad. Further evidence for genetic variation at the serotonin transporter gene SLC6A4 contributing toward anxiety. Psychiatric Genetics, 2017; 1 DOI: 10.1097/YPG.0000000000000171

Andreas Frick, Fredrik Åhs, Jonas Engman, My Jonasson, Iman Alaie, Johannes Björkstrand, Örjan Frans, Vanda Faria, Clas Linnman, Lieuwe Appel, Kurt Wahlstedt, Mark Lubberink, Mats Fredrikson, Tomas Furmark. Serotonin Synthesis and Reuptake in Social Anxiety Disorder. JAMA Psychiatry, 2015; DOI: 10.1001/jamapsychiatry.2015.0125

Brian A. Primack, Ariel Shensa, Jaime E. Sidani, Erin O. Whaite, Liu yi Lin, Daniel Rosen, Jason B. Colditz, Ana Radovic, Elizabeth Miller. Social Media Use and Perceived Social Isolation Among Young Adults in the U.S.. American Journal of Preventive Medicine, 2017; DOI: 10.1016/j.amepre.2017.01.010

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