A brain scan study suggests that a suspect gene may increase susceptibility to anxiety and depression by weakening a circuit for processing negative emotion. People with the depression-linked gene variant showed less gray matter and weaker connections in the mood-regulating circuit. How well the circuit was connected accounted for nearly 30 per cent of their anxious temperament, researchers at the National Institute of Health's (NIH) National Institute of Mental Health (NIMH) found.

"We discovered the mood-regulating circuit by using the gene to interrogate the imaging data," Weinberger explained adding, "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 centre 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.

"Until now, it's been hard to relate amygdala activity to temperament and genetic risk for depression," said Dr. Andreas Meyer-Lindenberg, a lead author. "This study suggests that the cingulate's ability to put the brakes on a runaway amygdala fear response depends upon the degree of connectivity in this circuit, which is influenced by the serotonin transporter gene," Dr. Andreas added.

Since serotonin activity plays a key role in wiring the brain's emotion processing circuitry during early development, the researchers propose that the short variant leads to stunted coupling in the circuit, a poorly regulated amygdala response and impaired emotional reactivity - resulting in increased vulnerability to persistent bad moods and eventually depression as life's stresses take their toll.