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Gene link to depression under question

22 June 2009
Appeared in BioNews 513

A new study published in the Journal of the American Medical Association has called into question a previously reported link between a gene variation and risk of depression. The study, funded by the National Institute of Mental Health (NIMH) and carried out by scientists from six US universities, was led by Dr Kathleen Merikangas from the NIMH Intramural Research program and Dr Neil Risch of the University of California, San Francisco.

In 2003, a highly publicised study suggested that a single gene mutation influences a person's risk of severe depression following stressful life events. The study looked at DNA samples from 847 individuals who have been followed from birth to age 26, and found that those with a variant in a gene involved in controlling the activity of serotonin had a much higher risk of depression. Serotonin is a chemical messenger that works in the brain and is known to affect mood. Problems in regulating serotonin are linked to depression, schizophrenia and anxiety disorders.

Dr Merikangas and Dr Risch's team attempted to replicate the 2003 study results in a much larger sample. They re-analysed the data of 14,250 participants involved in 14 studies published between 2003 and 2009, which could be directly compared to the original study. The researchers found a significant link between risk of depression and the number of stressful life events. However, they found no evidence for a link between the high risk variant of the serotonin-regulating gene and risk of depression.

Dr Avshalom Caspi, a neuroscientist at Duke University in Durham, US, who led the original research, told the New York Times 'What is needed is not less research into gene-environment interaction, but more research of better quality'. He added that it would be premature to abandon research in this area, especially when other evidence has linked the serotonin gene to an individual's sensitivity to stress.

The researchers emphasised that they did not want to discourage research into gene-environment interactions and depression. Dr Merikangas said 'Even though our re-analysis did not confirm an association between the serotonin gene and depression, the finding that the environmental factor was strongly associated with depression in several studies reminds us that environmental factors are also involved in the complex pathways leading to mental disorders'.

The authors wrote that 'it is critical that health practitioners and scientists in other disciplines recognize the importance of replication of such findings before they can serve as valid indicators of disease risk'.

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