Reduced
brain trapping of
a-[11C]methyl-L-tryptophan,
a proxy measure for serotonin synthesis, in
depressed patients
The
serotonin hypothesis of depression supposes a
reduced availability of serotonin
(5-hydroxytryptamine, 5-HT) in certain brain
areas involved in the regulation of mood.
Impairment of serotonin neurotransmission in
patients with major depression could result from
reduced availability of the precursor
L-tryptophan (Trp) for serotonin synthesis,
reduced metabolism and/or release, altered
reuptake, receptor function and transduction.
Reduction of 5-HT2 and
5-HT1A receptor binding, and 5-HT
transporter have been observed in the brain of
depressed patients. The object of a study was to
investigate serotonin synthesis in the brain of
patients with major depression, using
a-[11C]methyl-L-tryptophan,
a synthetic analogue of Trp, as an index of
serotonin synthesis since it can be related to
the metabolic conversion of Trp into
serotonin.
Seventeen medication-free outpatients with major
depression were compared to 17 controls. The
rate of the trapping of a-[11C]methyl-L-tryptophan
(K*) was measured in different brain regions
using the
a-[11C]methyl-L-tryptophan/positron
emission tomography (PET) method.
Normalized K* values were reduced bilaterally in
the anterior cingulate cortex in women with
depression, in the left side of the anterior
cingulate cortex in depressed men, and in the
left mesial temporal cortex in male and female
patients with depression. Volumetric analysis of
the subdivisions of the cingulate cortex
indicated that the reduction of normalized K* in
depressed patients was not due to a reduction in
gray matter areas.
Since anterior cingulate cortex is thought to
play a role in mood regulation, the reduction of
normalized K* in some parts of the limbic and
paralimbic cortices may be involved in the
biochemical changes linked to major depression.
This study thus provides additional evidence to
support a serotonergic dysfunction associated
with major depression. Rosa-Neto
P, Diksic M, Okazawa H, Leyton M, Ghadirian N,
Mzengeza S, Nakai A, Debonnel G, Blier P,
Benkelfat C. Measurement of brain regional
{alpha}-[11C]methyl-L-tryptophan
trapping as a measure of serotonin synthesis in
medication-free patients with major depression.
Arch Gen Psychiatry 61: 556-563,
2004.