HealthMethylation and the serotonin transporter molecule may predict anxiety

Methylation and the serotonin transporter molecule may predict anxiety

A new study released this month in Nature Neuroscience may have identified a biomarker that can predict and explain why some are more vulnerable to anxiety-related psychiatric disorders, including depression and Post-traumatic Stress Disorder.

The study, conducted by researchers at Duke University, examines the serotonin transporter molecule, which determines the amount of serotonin in the brain and remains one of the main targets when treating anxiety and mood disorders. It was previously found that different DNA sequences in this transporter gene contribute to exacerbated responses to stress in some individuals, responses which can lead to the development of depression or anxiety disorders.

However, this study focuses on methyl groups attached to the serotonin transporter DNA. These methyl groups determine when and where the transporter gene is active, and therefore contribute to the levels of serotonin present in the brain. The study shows that the presence of these methylation groups may be a reliable biomarker for mental illness risk.

Studying Methylation Levels

The researchers conducted the first part of their three-part study on a group of around 80 participants. These participants were shown images of angry or fearful faces, and their brain activity was monitored during the exercise. The researchers examined reactions to these images in the area of the brain responsible for response to threat and stress, called the amygdala. They also measured the levels of methylation in the serotonin transporter DNA by testing the participants’ saliva.

The Results

After examining the results, namely the levels of methylation, the researchers discovered that participants with higher levels of methylation on the serotonin gene expressed overall greater reactivity to the images. These heightened reactions in the amygdala are indicative of an exacerbated stress response, signaling heightened susceptibility to anxiety-related disorders.

The researchers were surprised to discover that even minute methylation differences were able to predict differences in amygdala reactivity. Methylation levels were more accurate predictors of stress reactivity than DNA sequence variation, the previous foremost indicator for anxiety disorders.

Confirming the Results

In order to replicate and further study the role of methylation in stress reactivity, the team conducted two additional studies. The first was conducted on 96 adolescents, aged between 11 and 15 years old, and the second on the brains of corpses. Both of these studies saw promising results, backing up the findings which linked methylation levels, serotonin levels, and stress reactivity in the amygdala.

Biomarkers of Mental Illness

The findings from all three studies also suggested that methylation levels could be passed down genetically rather than being acquired during the lifespan, indicating that the levels could be an important signal for future mental illness complications in children or adolescents. Head author of the study, Ahmad Hariri, commented that he hopes the results of this study will lead doctors and researchers to consider methylation as a more accurate predictor for anxiety-related mental illness risk than DNA sequence variation.


Yuliya S. Nikolova, Karestan C. Koenen, Sandro Galea, Chiou-Miin Wang, Marianne L. Seney, Etienne Sibille, Douglas E. Williamson and Ahmad R. Hariri. Beyond genotype: serotonin transporter epigenetic modification predicts human brain function. Nature Neuroscience, August 2014. DOI: 10.1038/nn.3778

Carla Nasca, Ph.D., is a post-doctoral fellow of the American Foundation for Suicide Prevention in the laboratory of Neuroendocrinology at the Rockefeller University, New York. Dr. Nasca received her B.A. in Molecular Biology and her M.S. in Electrophysiology from the University of Palermo in Italy. She earned her Ph.D. in Neurobiology and Pharmacology from the University Sapienza in Rome, Italy, before moving to The Rockefeller University under the mentorship of Dr. Bruce McEwen.

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