Depression traced to overactive brain circuit

A brain imaging study by the NIH's National Institute of Mental Health (NIMH) has found that an emotion-regulating brain circuit is overactive in people prone to depression even when they are not depressed. Researchers discovered the abnormality in brains of those whose depressions relapsed when a key brain chemical messenger was experimentally reduced. Even when in remission, most subjects with a history of mood disorder experienced a temporary recurrence of symptoms when their brains were experimentally sapped of tryptophan, the chemical precursor of serotonin, the neurotransmitter that is boosted by antidepressants.

Neither a placebo procedure in patients nor tryptophan depletion in healthy volunteers triggered the mood and brain activity changes. Brain scans revealed that a key emotion-processing circuit was overactive only in patients in remission whether or not they had re-experienced symptoms and not in controls. Since the abnormal activity did not reflect mood state, the finding suggests that tryptophan depletion unmasks an inborn trait associated with depression.

Alexander Neumeister, M.D., Dennis Charney, M.D., Wayne Drevets, M.D., NIMH Mood and Anxiety Disorders Program, and colleagues, report on their positron emission tomography (PET) scan study in the August 2004 Archives of General Psychiatry.

The NIMH researchers and others had previously shown that omitting tryptophan from a cocktail of several other essential amino acids washes out the precursor chemical from the blood and brain, depleting serotonin and often triggering symptoms in people with a history of depression and even in healthy people from depression-prone families. This added to evidence that a genetic predisposition that renders some people vulnerable to inadequate serotonin activity may be at the root of the mood disorder.

The researchers scanned subjects after their blood tryptophan levels were reduced by about three-fourths, using a radio

Contact: Jules Asher
NIH/National Institute of Mental Health

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