Depression Gene May Weaken Mood-Regulating Circuit

How Inherited Traits Affect Depression

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 percent of their anxious temperament, researchers at the National Institute of Health�s (NIH) National Institute of Mental Health (NIMH) found. Dr. Daniel Weinberger and colleagues report on their brain imaging genetics study in the May 8, 2005 online edition of Nature Neuroscience.

�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, boosts amygdala activity while viewing scary faces, and has been linked to anxious temperament. Yet, how it works at the level of brain circuitry remained a mystery.

Next: MRI Study Provides Insight in to Depression

Adapted from: Depression Gene May Weaken Mood-Regulating Circuit
(http://www.nimh.nih.gov/press/shortcircuit.cfm)

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