"We discovered the mood-regulating circuit by using the gene to interrogate the imaging data," explained Weinberger. "The brain handles information much like an orchestra. So we asked questions akin to 'Are the violin and the clarinet playing the same tune and to what extent might this gene account for it?'"
In this case, it turned out that the amygdala, a fear processing hub deep in the brain and the cingulate, an emotion-dampening center located near the front of the brain, were playing a duet under the baton of the depression-linked gene.
The gene codes for the serotonin transporter, the protein in brain cells that recycles the chemical messenger after it's been secreted into the synapse, the gulf between cells. Since the most widely prescribed class of antidepressants act by blocking this protein, researchers have focused on possible functional consequences of a slight variation in its DNA sequence across individuals. Everyone inherits two copies of the gene, one from each parent, which comes in two common versions: short and long. The short version makes less protein, resulting in less recycling, increased levels of serotonin in the synapse, and more serotonin-triggered cellular activity. Previous NIMH-supported studies had shown that inheriting the short variant more than doubles risk of depression following life stresses