Blood molecule predicts success of antidepressants


People who begin antidepressant treatment must face a grueling wait of several weeks before they find out whether or not the drug will work for them. A new take on the causes of depression could lead to a blood test predicting who will be helped by medication – taking the guess work out of prescribing.

“A test would be a major advance as at the moment millions of people are treated with antidepressants that won’t have any effect,” says Gustavo Tureckiof McGill University in Montreal, Canada, who led the study.

The research centres on miRNAs, small molecules that have an important role in turning genes on and off in different parts of the body. MiRNAs have already been implicated in several brain disorders.

In the latest study, Turecki and his colleagues measured the levels of about 1000 miRNAs in the brains of people who had committed suicide. These were compared to levels in brains of people who had died from other causes. A molecule called miRNA-1202 was the most altered, being present at significantly lower levels in the brains of people who died from suicide.

Crucially, this molecule seems to damp down the activity of a gene involved in glutamate signalling in the brain. That’s significant because recent research has highlighted the importance of glutamate signalling in depression.

The McGill team found that miRNA-1202, unlike most other miRNAs, is produced exclusively in humans and other primates. “That suggests this miRNA is involved in cognition,” says Yogesh Dwivedi of the University of Alabama in Birmingham, who was not involved in the study.

Blood samples taken from people about to start treatment with citalopram, one of the most widely used SSRIs – a class of antidepressant – showed that those who subsequently improved in response to the drug had about half the levels of miRNA-1202 as those who failed to respond. This suggests that measuring levels of the molecule could predict whether the antidepressant will be effective.

The next step, says Turecki, is to see if it also predicts response to other types of antidepressants. Promisingly, another drug called imipramine, which belongs to the second main class of antidepressants, had similar effects on miRNA-1202 to citalopram, when applied to neurons grown in the lab.

“MiRNAs are a hot topic in psychiatry now,” says Dwivedi. “They could help us understand the neurobiology of depression.” Dwivedi cautioned, however, that each miRNA can affect many different genes, so its involvement in depression may not be clear-cut.

Cosmo Hallström of Imperial College London says, although the results need replicating, a test to predict response to drug treatment would be very helpful. He points out, however, that it would need to give fast results, as psychiatrists would not want to delay starting people with severe depression on drugs that could help them.

Journal reference: Nature Medicine, DOI: 10.1038/nm.3582


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