The researchers studied a New Zealand family in which some members suffered from familial focal segmental glomerulosclerosis or FSGS, a type of kidney disease that can lead to complete kidney failure.

The scientists from Duke University Medical Center found a mutation in a gene called transient receptor potential cation channel 6 or TRPC6, in every family member who had FSGS.

This finding may well lead to more effective treatments for the disease, which is on the increase in the United States, particularly among African-Americans.

FSGS affects 20 percent of patients undergoing dialysis, a process where a patient's blood is pumped through a machine that filters out wastes and other products, a function the kidneys would normally do.

The report is published in Science Express and in the early online version of the journal Science.

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Next, using functional magnetic resonance imaging (fMRI), the researchers monitored the brain activity of 94 healthy participants while they were looking at scary faces, which activates fear circuitry. Those with the short variant showed less functional connectivity, in the same circuit.

Nearly 30 percent of subjects' scores on a standard scale of "harm avoidance," an inherited temperament trait associated with depression and anxiety, was explained by how well the mood-regulating circuit was connected.

"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."

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.

Other members of the NIMH team were: Dr. Lukas Pezawas, Dr. Bhaskar Kolachana, Dr. Michael Egan, Dr. Venakata Mattay, Emily Drabant, Beth Verchinski, and Karen Munoz. Dr. Ahmad Hariri, University of Pittsburgh, also participated in the study.

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