| MRI Study Provides Insight in to DepressionNew Ideas on How Some People Interpret the World Around ThemThe NIMH research team first scanned 114 healthy subjects using magnetic 
resonance imaging (MRI). Those with at least one copy of the short variant had less 
gray matter (neurons and their connections) in the amygdala-cingulate circuit than 
those with two copies of the long variant. 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 
with Dr. Lukas Pezawas. �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. 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.   Areas in the cingulate (right) and amygdala (left) that differed in gray matter 
volume between subjects with the short and long versions of the serotonin 
transporter gene. Short version carriers showed the greatest reductions in the red 
area, which previous studies have linked to depression.   Subjects with two copies of the long version (LL) of the serotonin transporter 
gene showed more functional connectivity between the amygdala (yellow) and the 
cingulate (red, blue), which are key components of a mood-regulating circuit.  Previous: Depression Gene May Weaken Mood-Regulating Circuit Adapted from: Depression Gene May Weaken Mood-Regulating Circuit(http://www.nimh.nih.gov/press/shortcircuit.cfm)
 
  
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