It's still not clear whether the popular medications have anything to do with the brighter mood among users. But the results do support the hypothesis that clogged-up blood vessels in the brain could play a role in depression, said Dr. Christian Otte.

"It is possible that statins exert beneficial effects on depressive symptoms through protective effects on cerebrovascular processes," Otte, of the Charité University Medical Center in Berlin, told Reuters Health by email.

Statins are some of the most widely used drugs worldwide. Between 2005 and 2008, a quarter of U.S. adults over 45 took the drugs, according to the National Center for Health Statistics.

While the drugs are generally considered safe, the U.S. Food and Drug Administration on Tuesday released a warning linking them to a slightly increased risk of diabetes and memory loss.

There have also been rare cases of liver and muscle damage related to statins.

To find out if the medications could have an effect on depression, Otte's group, which published its finding in the Journal of Clinical Psychiatry, tracked 965 people in California for several years. All of the participants had suffered a heart attack or had other signs of heart disease.

At the beginning of the study, 65 percent of the people were taking a statin, such as Lipitor, Crestor or Zocor.

Based on questionnaires about their mental health, 17 percent of statin users screened positive for depression at the beginning of the study compared to 24 percent of people not on the drugs.

Among those who had no mood problems initially, 18 percent of statin users and 28 percent of nonusers became depressed at some point over the six year study.

"I'm not surprised at these findings," said Dr. Charles Blatt of the Lown Cardiovascular Center in Brookline, Massachusetts, who was not involved in the new work.

In a smaller study from 2003, he found a similar link between statin use and lower rates of depression.

"It may point to the fact that this might not be an epiphenomenon, but biologically relevant," Blatt told Reuters Health.

But that's not at all clear, according to Susan Jick, a professor at Boston University School of Public Health, who wasn't linked to the study.

She pointed out that the researchers didn't track the medicine people took over time, meaning they couldn't tell who stopped or began taking statins. Statin users also had a lower risk of depression to begin with, and were less likely to be poor, have a history of depression or smoke.

"All of these things alone could explain the result," Jick told Reuters Health by email.

Although it's never possible to account for all possible differences, Otte countered that his team had ruled out several likely explanations.

Otte, who sits on the speakers board of several pharmaceutical companies, said future studies should look at statins and depression in other patient groups, especially those with risk factors for heart disease that aren't thought to require cholesterol-lowering medications.

Blatt said it's possible statins may also influence depression indirectly.

"We live in such a cholesterol-phobic nation, and if you have something that lowers your cholesterol, you feel better," he told Reuters Health.

But he added that the new study doesn't mean depression should be treated with statins.

"It's always nice to see a long-term study with more people in it wind up with a similar effect and scale of effect (as our study), but I'm not sure this really rocks the boat or changes our approach very much," he said.

SOURCE: bit.ly/zq7Y5s Journal of Clinical Psychiatry, online February 21, 2012.

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