Why Do Antidepressants Boost Suicidal Rates?

It's about two genes

The first step towards suicidal is depression. Paradoxically, antidepressants can boost a suicide risk in some persons. Now it is believed that two genes linked to chemical signaling in the brain are possible culprits for this.

Few years ago researches started to point that the antidepressant drugs rose the suicide risk in some adolescents and children. In 2003, UK forbade the use in minors of selective serotonin reuptake inhibitor (SSRI) drugs, and in 2004 the U.S. Food and Drug Administration warned that all types of antidepressants are a risk factor in children, adolescents and young adults.

But how antidepressants induce suicidal behavior or thoughts in some individuals was not known. Trying to explain this, the research team headed by Francis McMahon of the National Institute of Mental Health (NIMH) in Bethesda, Maryland, investigated 68 genes in 1915 adults with major depression who received citalopram, a SSRI.

The team detected two DNA markers (short sequences), in two genes, GRIA3 and GRIK2, that triggered a higher risk for suicidal thoughts while taking citalopram. GRIA3 and GRIK2 encode the receptors for glutamate, a brain molecule connected to learning and memory. A minute DNA change in these markers seems to increase the suicidal thoughts in those taking antidepressants.

The GRIA3 variation almost doubled the risk of developing suicidal thoughts, while the GRIK2 mutation increased the risk by 8 times! Those carrying both mutations, an extremely rare situation, had a 15 times higher risk.

"The findings suggest part of the tendency to develop this type of reaction to antidepressants might be genetically determined, and this might be used in the future to develop genetic screening tests to identify people who might be at risk. Still, the work needs to be replicated and at this point it's not clear why these particular genetic variations would contribute to suicidal thinking in people who take antidepressants," said McMahon.

But the new findings seem to be promising.

"They are leading the field into the potential for tailoring treatments to individual gene differences and new general targets for the treatment of depression," said Elliot Gershon, a psychiatric genetics researcher at the University of Chicago in Illinois.

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