Researchers tie depression to overactive brain circuit

AORN Journal, Oct, 2004

A study conducted by the National Institute of Mental Health (NIMH) has found that an overactive emotion-regulating brain circuit could cause depression, according to an Aug 3, 2004, news release from the National Institutes of Health. Researchers discovered this abnormality in brains of people whose depression relapsed when tryptophan--a key brain chemical messenger--was reduced experimentally.

Most study participants with a history of mood disorder experienced a temporary recurrence of depressive symptoms when their brains were experimentally sapped of tryptophan, the chemical precursor of serotonin (ie, the neurotransmitter boosted by antidepressants). Neither a placebo administered to patients with depression nor tryptophan depletion in healthy volunteers triggered the same mood and brain activity changes. Brain scans revealed that a key emotion-processing circuit was overactive only in patients in remission--regardless of whether they had re-experienced symptoms--and not in individuals in the control group. The abnormal activity did not reflect mood state, suggesting that tryptophan depletion unmasks an inborn trait associated with depression.

The NIMH researchers and others had previously demonstrated that omitting tryptophan from a mix of several 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 with depression-prone family members. This, added to evidence that a genetic predisposition makes some people vulnerable to inadequate serotonin activity, may be a root cause of depression.

The researchers scanned study participants after their blood tryptophan Levels were reduced by approximately three-fourths, using a radioactive tracer (ie, a form of glucose) that reveals where the brain is active during a particular experimental condition. They randomly gave 27 unmedicated, patients with depression in remission and 19 control group participants either pills containing seven essential amino acids (eg, lysine, valine) or identical-looking placebo pills. Participants received either the active pills or placebos in repeated trials over several days in a blind, crossover study.

Sixteen (59%) of the patients experienced a transient return of symptoms after tryptophan depletion, and their moods returned to normal by the next day. Compared to participants in the control group, the patients showed increased brain activity in a circuit coursing through the front and center of the brain--areas that are involved in regulating emotions and motivation and that have been implicated in previous studies on depression. Whereas previous studies interpreted the circuit activation as a transient, mood-dependent phenomenon, the new evidence suggests that circuit overactivation likely is an underlying vulnerability trait, according to the researchers. Based on this, they suggest that tryptophan depletion may be a useful tool for studying the genetic basis of depression because of its ability to unmask what appears to be a trait marker for major depressive disorder.

Depression Traced to Overactive Brain Circuit (news release, Bethesda, Md: National Institutes of Health, Aug 3, 2004) http://www.nih.gov/news/pr/aug2004/nimh -03.htm (accessed 18 Aug 2004).