People with depression have an over-active brain circuit that can stay turned on even when they are not feeling down, US Researchers reported.

The finding suggests that some depressed patients remain vulnerable all the time, and need to stay on medication even after they get better, the researchers said.

Researchers at the National Institute of Mental Health deliberately induced some symptoms of depression in patients to image their brains using positron emission tomography or PET scans.

They can do this by giving the patients a cocktail of amino acids, said Dr. Alexander Neumeister, a researcher now at Yale University in Connecticut.

The correct mix lowers levels of the amino acid tryptophan. The body converts tryptophan into serotonin, the neurotransmitter - message-carrying chemical - that is boosted by many antidepressants.

"That happens very fast - within five hours," Neumeister said in a telephone interview.

They tested 27 people who had been treated for depression but who were currently feeling healthy and taking no medication, and compared them to 19 people who had never had depression.

About 60 per cent of the former depression patients had their symptoms come back temporarily when their tryptophan was depleted, Neumeister said.

PET scans showed abnormal activity in certain brain regions known to be associated with depression in the front and centre of the brain, such as the orbitofrontal cortex, the thalamus, anterior cingulate, and ventral striatum.

But interestingly, said Neumeister, the same thing happened in the 40 per cent of depression patients who did not feel any symptoms.

And, writing in the Archives of General Psychiatry, Neumeister and colleagues said none of the 19 non-depressed patients showed this same pattern of brain activity, even when their tryptophan was lowered.

"This shows something is really wrong in this particular circuit," Neumeister said. "It suggests that medication cannot correct the underlying biology. It is another argument that people should stay on their medications."

Who is vulnerable to depression?

Neumeister and colleagues are searching for the genetics that underlie depression and say their study may provide a valuable tool.

"We may be able to define a group who are vulnerable to depression in general," he said. "And we can see which treatment they respond to."

In the study, people ate turkey or bananas or other tryptophan-rich foods to recover from the effects of the test. Unfortunately, that does not help in real life, Neumeister said.

Several other studies have shown changes in brain structure in people with depression, notably in the hippocampus. And at least one study has suggested that patients who take antidepressants may see a regeneration of brain cells.

Experts say that 16 per cent of Americans, or more than 30 million people, may suffer major depression at some point in their lives. The NIMH says major depression is the top cause of disability around the world.

(Agencies August 19, 2004)