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New neuroimaging research highlights interplay with genes and environment as risks for major depression

JULY 10, 2008

Dr Simon Surguladze, Clinical Lecturer at the Institute of Psychiatry, King’s College London, and colleagues, have published an important new study  entitled “Genetic variation in the serotonin transporter modulates neural system-wide response to fearful faces”  in the July issue of the journal Genes, Brain and Behavior.
Previous research has demonstrated that, if exposed to multiple stressful events, people with a certain (short allele) variant of the serotonin transporter gene are more likely to develop major depression compared with those who have different, long allele of the same gene. The short allele is not particularly rare and could be present in approximately 19% of healthy population -  it is the interplay of the genes and environment that constitutes the risk of developing the disorder. 
There have been studies that found that people with short allele show hyper-activity in amygdala when exposed to emotionally negative pictures   This finding of overactive amygdala in short allele carriers has been suggested to underlie the vulnerability to depression. 
The study conducted at the Institute of Psychiatry demonstrated that the effect of the genotype was system-wide rather than localized in any brain structures, e.g. amygdala. The functional magnetic resonance imaging experiments involved healthy subjects watching fearful or non-emotional facial expressions. Although not overly stressful, the fearful expressions are known to represent a good indicator that signals the danger of the condition.

The researchers showed that in short allele carriers, compared with those with long allele, there was the higher degree of joint activation of amygdala and the visual cortex, as well as visual cortex and parts of frontal cortex. These results help to better understand how the brain reacts to the emotionally salient signals. In particular, the brain networks that are responsible for visual perception, emotion processing and emotion appraisal may get over active in some people with the short allele polymorphism. This hyper-vigilance has the advantage of protecting an individual in dangerous situations, but is not a helpful way of coping with the chronic exposure to stress.
For full details of the paper please refer to: Genes Brain Behav. 2008 Mar 18. Genetic variation in the serotonin transporter modulates neural system-wide response to fearful faces. Surguladze SA, Elkin A, Ecker C, Kalidindi S, Corsico A, Giampietro V, Lawrence N, Deeley Q, Murphy DG, Kucharska-Pietura K, Russell TA, McGuffin P, Murray R, Phillips ML. Institute of Psychiatry, King’s College London, London and Department of Adult Psychiatry, Whitchurch Hospital, Cardiff, United Kingdom.
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