Genetics Play a Role in Social Anxiety Disorder, Study Finds

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

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’s researcher 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 fearbeing 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.

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.
References: Psychology Today
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.

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SCIENCE CLOSER TO EXPLAINING THE ORIGINS OF LIFE

Chemists believe that they may have found how reactions on early Earth may have given rise to molecules vital for genetics and energy metabolism.

The molecular dance that led to the origin of life billions of years ago remains one of the deepest mysteries in modern science. Although the exact choreography is forever lost to time, scientists now say that they may have identified one of the key steps. Chemists in Germany today reported a plausible way in which basic chemicals available on early Earth may have given rise to compounds called purines, which are:

"Natural substances found in all cell bodies, and in virtually all foods, purines provide part of the chemical structure of our genes and genes of plants and animals. A relative small number of meals, however, contain concentrated amounts of purines. In most, these foods high in purines foods are also high in protein. Purines are a key ingredient of DNA, RNA and energy metabolism in our cells."

The new work is “very pretty chemistry”, says Gerald Joyce, a chemist at the Scripps Research Institute in San Diego, California. Joyce specializes in the chemistry that may have given rise to life.

Joyce along with others have long suggested that one of the key early events in this process was the formation of RNA; a long chainlike molecule that conveys genetic information, and speeds up other chemical reactions. Both of those functions were necessary for life to evolve. However, sorting out how RNA itself may have arisen, and led to an “RNA world” that has certainly been a struggle.

RNA is made up of four different chemical building blocks which are the following; adenine (A), guanine (G), cytosine (C), and uracil (U). Seven years ago, researchers led by the U.K. chemist John Sutherland showed a plausible series of steps by which chemical reactions on early Earth could have synthesized cytosine and uracil, also known as pyrimidines. However, this route hasn’t been shown to give rise to adenine or guanine which are RNA’s purine building blocks. Others partially succeeded in the purine quest.



In 1972, the U.K. chemist Leslie Orgel along with his colleagues suggested one possible route for purine formation on early Earth. This never seemed all that plausible, says Thomas Carell, a chemist at Ludwig Maximilian University of Munich in Germany. That’s in part due to the process producing only tiny amounts of the purines that are so vital for life.

“People have been looking for synthetic routes to making purines for 40 years,” Carell says.

Carell and his colleagues stumbled upon a new lead several years ago, when they were studying how DNA is damaged. DNA is very similar to RNA except for that uracil is replaced with thymine. The group was studying how a molecule called formamidopyrimidine (FaPy) reacts with DNA, and found that it also readily reacts to form purines. Consequently, they decided to look into whether early Earth conditions could have given rise to FaPys, and thus, purines.

The first step was easy as it only requires hydrogen, cyanide, and water. Hydrogen cyanide, a simple molecule containing only three atoms ( Hydrogen, Nitrogen, and Carbon) is widely believed to have been abundant on early Earth. This molecule readily reacts in water (also thought to be plentiful at the time) to form one class of molecules called aminopyrimidines, which contains several chemical groups called amines. Normally, these amines react indiscriminately to form a wide mix of different compounds. That’s a bad thing in this case, Carell explains, because most of those products wouldn’t be purines.



Carell needed to find a way to stop all but one critical amine from reacting. “Initially I thought this would never work,” Carell says. However, the solution, he says, was far simpler than he expected. When Carell’s team spiked their solution with just a bit of a certain acid, (also widely considered abundant on early Earth) the reaction caused an extra proton from the acid to attach to the aminopyrimidine. That extra proton killed the reactivity of all but one of the amine groups on the molecule. Subsequently, much to Carell’s delight, the lone amine that stayed reactive was precisely the one that reacts to form a purine.

But wait, that’s not all. Further lab results presented today in Science show that the reactive amine on the aminopyrimidine readily bonds with either formic acid or formamide. Last year, the Rosetta space probe detected both of those chemicals on a comet, and now scientists think that they also probably rained down on early Earth. Once the bonds have formed, products of those reactions then eagerly react with sugars to create large quantities of purines. “It’s like a domino cascade,” Carell says.

Mic drop? Not so fast, says Steven Benner, a chemist and origin of life expert at the Foundation for Applied Molecular Evolution in Alachua, Florida. Benner agrees that the newly suggested purine synthesis is a “major step forward” for the field. But even if it is correct, he says, the chemical conditions that gave rise to the purines still don’t match those that Sutherland’s group suggests may have led to the pyrimidines. So just how A’s, G’s, C’s, and U’s would have ended up together has yet to be elucidated. Also, even if all the RNA bases were in the same place at the same time, it’s still not obvious what drove the bases to link up to form full-fledged RNAs, Benner says.



We’re here, so as a result, it must have happened somehow. But, RNA-world researchers still need to line up a few more dominoes before one of the greatest mysteries of life will be truly solved.

Source:
Robert F. Service

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