Overactive Brain Circuit Faulted for Depression

The finding was reported in the August 2004 issue of Archives of General Psychiatry.

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 boosted by antidepressant medications.

Neither a placebo procedure in patients nor tryptophan depletion in healthy volunteers triggered the mood and brain activity changes. The scans revealed that a key motion-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.

The researchers scanned subjects with positron emission tomography (PET) after their blood tryptophan levels were reduced by about three-fourths, using a radioactive tracer that reveals where the brain is active during a particular experimental condition. Pills containing seven essential amino acids or identical-looking placebo pills were given randomly to 27 unmedicated depressed patients in remission and 19 controls. Sixteen patients experienced a transient return of symptoms under tryptophan depletion, but their mood lifted to normal by the next day. Compared to controls, the patients showed increased brain activity in areas involved in regulating emotions.

"Since brain function appears to be disregulated even when patients are in remission, they need to continue long-term treatment beyond the symptomatic phase of their illness,” noted Dr. Alexander Neumeister, one of the authors of the study, conducted by the U.S. National Institute of Mental Health (Bethesda, MD, USA).




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