Serotonin synthesis is lower in the cortical areas of female than male healthy participants as measured with α-[ 11 C]methyl-L-tryptophan positron emission tomography

Dysregulation of the brain serotonergic system is a contributing factor to mood disorders. There are also reports suggesting a greater incidence of mood disorders in female patients. Serotonin (5-HT) synthesis is the first important step in serotonergic neurotransmission. The study of brain 5-HT synthesis was greatly improved by development of the α-[11C]methyl-L-tryptophan (α-MTrp) positron emission tomography (PET) imaging method. We reported before that 5-HT synthesis is reduced more in female than male subjects after tryptophan depletion, and that there are some region specific differences in 5-HT synthesis between male and female controls and patients with major depression. The objective of the present investigation was to compare 5-HT synthesis in male and female subjects using Statistical Parametric Mapping (SPM-2). Twenty-eight female (mean±Standard Deviation (SD); 33.2±17.2 years) and thirty-one male (29.8±12.8 years) healthy volunteers were scanned for sixty minutes, and venous blood samples were taken at progressively increasing time intervals after injection of up to 10 mCi of tracer. The functional images of the brain trapping constant, which was shown in rats to correlate with 5-HT synthesis, were transferred to the standardized 3-D space and colocalized with each participant's MRI. The final functional images had a resolution of 8.2×9.5×10.5 mm. The voxel based comparison was done using clusters with 100 voxels and with the height p<0.001. There was no cluster in which synthesis was greater in females than that in males, while there are seven clusters in which synthesis was lower in females than in males. The clusters showing difference are (see Figure 1): left frontal lobe middle and inferior frontal gyrus (BA 44), left and right parietal lobe supramarginal gyrus, left and right inferior parietal lobe (BA 40), left temporal lobe superior temporal gyrus, left limbic lobe cingulate gyrus and right posterior cingulate, right occipital lobe (precuneus; BA31), and left inferior frontal gyrus (BA 44 and BA 45). It is interesting to note that only cortical areas show significant differences between two genders. Because a relatively large cluster size was used in the comparisons smaller structures such as the amygdala and raphe nuclei would be missed. Some of the structures (e.g. cingulate, frontal lobe) showing a difference in synthesis between male and female subjects have been suggested to be involved in mood disorders. The lower 5-HT synthesis in female participants may be related to the higher incidence of affective disorders in that group.

Figure 1

Clisters of SPM2 analysis; synthesis in females<males.