An acne treatment blamed for triggering suicides in severely affected young people has been shown to cause depressive behaviour in animal tests, say researchers.
The finding lends support to claims that the drug, not the acne, may have led to the affected individuals taking their own lives.
The drug, Roaccutane, has been a focus of controversy for a decade over claims that it causes depression in vulnerable people.
The families of two English students who killed themselves after taking it blamed it for causing their deaths.
But psychiatrists say severe acne can lead to isolation and loneliness, triggering depression.
Jon Medland, 22, had started a course 3 1/2 weeks before he killed himself in Devon, southwest England, in 2004.
He was in the final year of a medical degree at Manchester University. His family called for a worldwide inquiry into the drug.
David Roberts, 21, had been taking it for two months when he hanged himself near his Liverpool home last year.
In the new study, Sarah Bailey from the University of Bath and Michelle Lane from the University of Texas found that when the drug was given to mice it left the animals immobile for longer periods than normal during stress tests.
Dr Bailey said further research was needed to establish whether the drug produced the same reaction in humans.
"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 the 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."
The research is published in the journal Neuropsychopharmacology.
Roche, the manufacturer, said there was no proven link between Roaccutane and suicide but the company was "constantly monitoring all available safety databases on Roaccutane worldwide".
The drug had "revolutionised the management of acne and helped improve the well-being of many patients by clearing the acne and preventing any new scarring", it said.
"Unfortunately, severe acne can cause some sufferers to become depressed and can also affect their mood and self-esteem."
Roaccutane carries a risk of liver damage and patients must be carefully monitored during treatment.
Further courses may be needed if the condition does not improve during the first six months of treatment.
In 1997 Seumas Todd, the 20-year-old son of veteran actor Richard Todd, killed himself with a shotgun after taking Roaccutane.
His father, who starred in the classic film The Dam Busters and Alfred Hitchcock's Stage Fright, claimed the drug was a factor in his death.
New Zealand claims
Critics of Roaccutane in this country have also claimed that the anti-acne drug is linked to mental illness and suicide.
The most notable case involved Hugo Wilkinson, who in 2000 committed suicide at the age of 19 - about three months after he started taking Roaccutane for severe acne.
His parents, John and Henrietta Wilkinson, blamed his death on the drug and called for it to be banned.
However, in 2003 coroner Sarn Herdson ruled there was no proven causal link between the drug and mental disorders or suicide. She said Hugo's mental illness might have started before he began using Roaccutane.
About 5000 New Zealanders take Roaccutane or Oratane, both of which contain the anti-acne ingredient isotretinoin.