The serotonin hypothesis of depression invokes a relative or absolute
deficit of serotonin neurotransmission. Reduced synthesis of serotonin in
the brain pathways mediating the expression of mood (ie, the limbic cortex)
is a plausible candidate mechanism.
To measure and compare, using the α-[11C]methyl-L-tryptophan/positron emission tomography method, the brain trapping
constant of α-[11C]methyl-L-tryptophan (K*,
milliliters per gram per minute), an index of serotonin synthesis, in brain
areas involved in the regulation of mood in patients with major depression
(MD) and age- and sex-matched controls.
Department of Psychiatry and Montreal Neurological Institute, McGill
Seventeen medication-free outpatients with a current episode of MD (9
women: mean ± SD age, 41 ± 11 years; 8 men: mean ± SD
age, 41 ± 11 years) and 17 controls (9 women: mean ± SD age,
37 ± 15 years; 8 men: mean ± SD age, 32.5 ± 9.9 years).
Main Outcome Measure
Normalized K*, normalized to the global mean, was measured in the dorsolateral
prefrontal, anterior cingulate, and mesial temporal cortices; the thalamus;
and the caudate nucleus.
Compared with age- and sex-matched controls, normalized K* was significantly
decreased bilaterally in female patients with MD in the anterior cingulate
cortex, in the left anterior cingulate cortex in male patients with MD, and
in the left mesial temporal cortex in male and female patients with MD (P<.001 for all). Exploratory analyses identified additional
patient-control differences for normalized K* (eg, inferior frontal gyrus
and superior parietal lobule), most of which, once corrected for 38 multiple
comparisons, lost their significance. Morphometric measurements of the cingulate
cortex divisions confirmed that the reduction of normalized K* in depressed
patients was not attributable to a reduction in gray matter volume. Normalized
K* in the anterior cingulate cortex did not correlate with ratings of depression
severity collected at the time of scan.
Reduction of normalized K*, an index of serotonin synthesis, in parts
of the limbic and paralimbic cortices may contribute to the biochemical alterations
associated with MD.