Genetic variation linked to anxiety could inform personalized interventions

Individual variation in genes alters our ability to regulate emotions, providing new insights that could help in the development of personalized therapies to tackle anxiety and depression, according to a new study published in the Proceedings of the National Academy of Sciences.

Researchers looked at marmoset monkeys to examine how variation in the serotonin transporter gene has an impact on the number of a specific type of serotonin receptor, known as the type 2A receptor, in a specific brain area. Receptors are proteins in the brain that enable particular molecules, in this case serotonin, to affect the function of nerve cells. Monkeys carrying the variant of the gene associated with high anxiety had lower numbers of this receptor, hence changing the way in which serotonin-based drugs act upon them.

Medicines targeting these receptors have recently been used in the treatment of anxiety and mood disorders, so these findings suggest that it could be important in the future to know what variant of the serotonin transporter gene an individual is carrying when deciding on a treatment strategy, researchers said.

The specific brain area where the number of receptors was reduced was the insula cortex, an important site for integrating information about sensations coming from the body with cognitive information processed in other areas to generate feelings and self-awareness, and to help guide decision-making.

Some individuals are at greater risk of developing anxiety and depression than others and this depends in part upon the interaction between our genes and our environment, such as stressful or adverse events in our lives. Moreover, some of those who develop anxiety or depression may respond better to treatment while others struggle to benefit.

In previous studies, researchers showed that variants of the gene also affected how a monkey responds to certain medicines. Specifically, individuals carrying the variant of the gene associated with high anxiety increased their anxiety towards a threat immediately after treatment with a commonly used antidepressant known as a selective serotonin re-uptake inhibitor (SSRI). This so called anxiogenic effect is often seen in patients in the early stages of treatment and is thought to be part of the reason why these patients do not respond favorably to SSRIs.

The new finding suggests that those cognitive behavioral therapies (CBT) that focus on controlling sensations from the body could help patients in whom SSRI drugs are not effective, according to Andrea Santangelo, PhD, co-author of the study and professor at the University of Cambridge in the U.K.

“As many as one in three people affected by anxiety and depression does not respond to anti-depressants, so we need to find better treatments to help improve their quality of life," said Santangelo in a statement. “Our research suggests that differences in our DNA may help predict which of us will respond well to these medicines and which of us require a different approach. This could be assessed using genetic testing."