On the Threshold of Eternity, by Vincent van Gogh. New research suggests that the antidepressant Prozac might be ineffective for a quarter of the population.
Credit: The Yorck Project
SYDNEY: Prozac may be ineffective in people with a common mutation in the brain, suggesting that a quarter of the 54 million who have taken the drug since its release may have been wasting their time, a new study shows.
Using mice as a model for the way the human brain functions, a team led by Francis Lee from Cornell University in New York examined a gene which contains the instructions to produce a protein called brain-derived neurotrophic factor (BDNF). They compared mice with a mutation in this gene with normal mice.
Out of the millions of units that make up a strand of DNA, it only took one change to a single unit to create the BDNF mutation, said the paper which is published today in the U.S. journal Science.
BDNF acts on brain cells to support their survival and encourage their growth and development. Low BDNF levels have been linked with depression and other mood disorders, although the exact mechanism has not been identified, according to the paper. Furthermore, the presence of the BDNF protein has been shown to help diminish stress and anxiety-related behaviours.
“The power of the mouse model is that additional behavioural abnormalities potentially associated with this genetic alteration can be assessed in a ... manner that would not be possible in human studies,” said Lee.
The mice received the drug commonly known as Prozac for 21 days prior to participating in two tests. In one test, the mice were timed as they explored an open area. Normal mice on Prozac spent more time in the centre of the test area, showing the drug’s effectiveness at reducing anxiety. However, mice afflicted with the BDNF mutation exhibited anxious behaviours, spending less time in the middle, even after receiving their Prozac.
The other test consisted of training mice to approach sweetened milk in their home cage, and then placing them in a brightly lit cage with the milk, said the paper. The time it took the mouse to approach the bowl of milk was a measure of the mouse’s anxiety level.
Normal mice approached the bowl faster than their counterparts with the BDNF mutation, according to the results. Even long-term Prozac treatment of BDNF mutation mice did not reduce their apparent anxiety.
Lee said these tests showed that the BDNF mutation seemed to increase anxiety, a behaviour that had not yet been established in humans with the BDNF mutation.
The BDNF mutation is common among humans, appearing in 20 to 30 per cent of the Caucasian population, according to the study.
“The findings cannot yet guide antidepressant treatment decisions,” Lee said. “However, this discovery provides one possible avenue of how, in the future, psychiatrists will be able to offer treatments options that are tailored for individual patients, based on genetic information.”
