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OVERACTIVE BRAIN CIRCUIT
| Article : Serotonin & Mental Health
Many psychiatric disorders are ‘caused’ by problems with...
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 radioactive
tracer (a form of glucose, the brain's fuel) which reveals where the brain
is active during a particular experimental condition. They randomly gave 27
unmedicated depressed patients-in- remission and 19 controls either pills
containing seven essential amino acids, such as lysine and valine, or
identical-looking placebo pills. Subjects received either the active pills
or placebos in repeated trials over several days in a blind, crossover
design. Sixteen (59 percent) of the patients experienced a transient return
of symptoms under tryptophan depletion; their mood lifted to normal by the
next day. Compared to controls, the patients showed increased brain activity
in a circuit coursing through the front and center of the brain (orbitofrontal
cortex, thalamus, anterior cingulate, and ventral striatum) - areas involved
in regulating emotions and motivation that have been implicated in previous
studies of depression. Whereas previous studies interpreted the circuit
activation as a transient, mood-dependent phenomenon, the new evidence
suggests that circuit over- activation is likely an underlying vulnerability
trait, say the researchers. Because of its ability to unmask what appears to
be a trait marker for major depressive disorder, the researchers suggest
that tryptophan depletion may be a useful tool for studying the genetic
basis of depression. "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 Neumeister, who
recently moved to the Yale University psychiatry department. Also
participating in the research were: Drs. Allison Nugent, Tracy Waldeck, Omer
Bonne, Earl Bain and Marilla Geraci, David Luckenbaugh, NIMH; Dr. Markus
Schwarz, Munich University Hospital of Psychiatry, Dr. Peter Herscovitch,
NIH Clinical Center PET Department. NIMH is part of the National Institutes
of Health (NIH), the Federal Government's primary agency for biomedical and
behavioral research. NIH is a component of the U.S. Department of Health and
Human Services. |
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