A popular treatment for severe acne has been found to produce depressive behaviour in mice.
The drug is highly effective acne treatment
University of Bath scientists tested Roaccutane after claims it has caused depression and suicide in patients since its introduction in 1982.
Their work, published in the journal Neuropsychopharmacology, is the first to back up these reports with firm scientific evidence.
The drug's maker, Roche, does include a warning about depression in packets.
However, the chemical mechanism by which this might happen has never been established.
Roaccutane is usually only prescribed to teenagers with particularly severe acne, but it is highly effective and has been used by approximately 13 million patients world-wide.
The Medicines and Healthcare products Regulatory Agency had received 1,588 reports of suspected adverse events experienced by people taking the drug up to this month. This included 25 people who died from suicide.
The Bath team, working with colleagues at the University of Texas at Austin, gave Roaccutane to adolescent mice over a six-week period, and monitored the animals' behaviour.
They found that while there was no change in the physical abilities of the mice, the rodents spent significantly more time immobile in a range of laboratory assessments designed to test their response to stress.
This was interpreted as a sign that the animals were exhibiting signs of depression.
Researcher Dr Sarah Bailey said: "Without more research it is difficult to say for sure whether the same link applies to people taking the drug.
"However, establishing a link between the active molecules within the drug and a change in depression-related behaviour, albeit in mice, is an important step forward in our understanding of the effects of this drug in the wider context of brain function.
"To date, the only evidence for any link with patients has come from individual case reports and such patient data is complicated by the psychosocial effects of having severe acne.
"This laboratory evidence provides a useful model for future research into Roaccutane and understanding how this family of compounds affects the brain."
Advice to users
Dr Bailey said teenagers should not stop taking the drug, but seek medical advice if they started to feel depressed. Parents should also watch out for any mood changes in their children.
It is not clear how the drug might cause depression. It is possible that it may lower levels of key brain chemical responsible for mood called serotonin, or it may somehow block the formation of new brain cells.
Roaccutane belongs to a group of medicines called retinoids - vitamin A-related compounds known to affect development of the nervous system.
For this reason the drug is not prescribed to pregnant women.
Previously scientists thought that retinoids were only important in the development of the nervous system.
However, it is now suspected that they may also regulate different aspects of brain function in adults, and play a role in the development of Alzheimer's disease and schizophrenia.
Roche issued a statement welcoming the research, but said a small study in mice was not necessarily indicative of the effects in humans.
The company said Roaccutane had revolutionised the treatment of severe acne.
But it added: "Unfortunately, severe acne can cause some sufferers to become depressed and can also affect their mood and self esteem.
"This is why the information provided with Roaccutane carries a warning that some patients may experience mood changes, including an increase in depression."