Gene-based anti-depressant treatment

Two studies published this week in the journal Science, and in the Journal of the American Medical Association (JAMA) may help identify the most effective type of anti-depressant medication for individuals, depending on their genetic makeup.

Currently, treating people for depression or chronic anxiety is a case of trial and error, before hopefully hitting on a drug that works. Up to 60 per cent of patients do not respond to the first medication they are prescribed. Moreover, the drugs available take a number of weeks before they begin to work, meaning trying to find the right treatment can be a difficult task.

The researchers at the Weil Medicinal College of Cornell University focused their studies on a particular brain mutation which predisposes humans to depression and other related disorders. They genetically engineered mice to express the same mutation and showed that they then displayed classic symptoms of rodent anxiety. Moreover, when the mice were treated with fluoxetine (or Prozac) this appeared to have little effect on the mice's behaviour.

Lee and colleagues, who carried out the research, say that variations in a serotonin transport gene could accurately predict which patients would respond to selective serotonin reuptake inhibitor (SSRI) drugs, of which Prozac is one. These drugs are widely used to treat depression, and work by increasing the amount of serotonin available to neurons in the brain. However, the mutation studied by Lee occurs in 20-30 per cent of Caucasians, suggesting that they may not respond to this type of treatment. Lee told Nature 'Because antidepressants have a delayed onset of action, knowing which class to initiate treatment with would be beneficial'.

In the JAMA study, workers at the Samsung Medical Centre in Seoul looked at key variations in the serotonin transport gene, as well as those in the norepinephrine transporter (NET) gene. Variations in the NET gene suggest treatment with a class of drugs called norepinephrine reuptake inhibitors (NRI's). The researchers tracked the outcomes of a group of 241 Koreans diagnosed with major depression. Participants were treated for six weeks with an SSRI or NRI. They confirmed that responses to both drugs were associated with genetic variations in the patients' genes.

Critics warn that this research may not revolutionise depression treatment, but may simply provide another useful piece of the puzzle to help individualise treatment. Others caution that this type of technology may still be a long way off. Sarah Bailey, a pharmacologist at the University of Bath, UK, told Nature, 'That kind of pharmacogenomics is something for the future. Doctors should go on prescribing SSRI's for now'.