Brain regional α-[11C]methyl-L-tryptophan trapping, used as an index of 5-HT synthesis, in healthy adults: absence of an age effect

Abstract

Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional alpha-[(11)C]methyl-L: -tryptophan (alpha-[(11)C]MTrp) trapping rate constant (K*; microl.g(-1).min(-1)), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis. Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with alpha-[(11)C]MTrp [18 males aged 46.6 +/- 22.2 years (range 20-80 years) and 18 females aged 33.0 +/- 15.5 years (range 20-80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm. VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and alpha-[(11)C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis. The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process.