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Anxious and Depressed Teens and Adults: Same Version of Mood Gene, Different Brain Reactions

Science Update

An NIMH study using brain imaging shows that some anxious and depressed adolescents react differently from adult patients when looking at frightful faces. This difference occurs even though the adolescent and adult patients have the same version of a mood gene. Researchers in the NIMH Mood and Anxiety Disorders Program and colleagues reported these findings online October 31, 2008, in the journal Biological Psychiatry.


Anxiety and depression are influenced by the processing of the mood-regulating brain chemical called serotonin. A protein known as the serotonin transporter directs serotonin from the space between nerve cells back into the cells, where it can be reused. Changes in the gene that codes for the serotonin transporter can lead to decreased transport of serotonin back into the brain’s nerve cells. Abnormalities in the serotonin system are associated with anxiety and depression.

Everyone inherits two copies of the serotonin transporter gene—one from each parent. The gene has various versions—one version is short, and one version is long. A person may have two copies of the same version or one copy each of two different versions. Previous studies in adults have linked versions of the gene to increased risk for mood and anxiety disorders. Adults who have one copy of the short version tend to be more anxious and depressed than adults who have two copies of the long version.

Previous brain imaging studies in adults linked gene versions to different responses of the brain’s fear hub—the amygdala—to frightful faces. In both healthy and affected adults who have at least one copy of the short version, the amygdala reacts more than it does in healthy or affected adults who have two copies of the long version of the gene. Whether these findings in adults also hold true for adolescents was unknown.

Using functional magnetic resonance imaging (fMRI), Jennifer Y. F. Lau, Ph.D., then at NIMH and now at the University of Oxford, U.K., and colleagues at NIH scanned the brains of 33 healthy teens and 31 teens with depression and anxiety disorders while they viewed pictures of frightful faces. Then the investigators compared the amygdala reactions in the two groups.

Findings of This Study

Lau and colleagues found that in healthy adolescents who have at least one copy of the short version of the gene, the amygdala reacts more than it does in healthy adolescents who have two copies of the long version. This result is the same in healthy adults. However, in anxious or depressed adolescents, the opposite results were found. In affected adolescents who have at least one copy of the short version, the amygdala reacts less than it does in affected adolescents who have two copies of the long version.


This finding in affected teens with two long version genes is the opposite of that observed in anxious or depressed adults. It is surprising because anxiety and depression during adolescence tend to predict these disorders during adulthood.

What’s Next?

The unexpected finding may be explained by the fact that anxious adults and anxious adolescents react differently when presented with threats. But further research is needed to fully understand the difference, the investigators say.


Lau JY, Goldman D, Buzas B, Fromm SJ, Guyer AE, Hodgkinson C, Monk CS, Nelson EE, Shen PH, Pine DS, Ernst M. Amygdala Function and 5-HTT Gene Variants in Adolescent Anxiety and Major Depressive Disorder . Biological Psychiatry. 2008 Oct 23. [Epub ahead of print].