Brain regional α-[11C]methyl-L-tryptophan trapping, used as an index of 5-HT synthesis, in healthy adults: absence of an age effect
- 124 Downloads
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 α-[11C]methyl-L-tryptophan (α-[11C]MTrp) trapping rate constant (K*; μl·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 α-[11C]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 α-[11C]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.
KeywordsPositron emission tomography 5-HT α-MTrp brain trapping Serotonin synthesis Brain morphometry Voxel-based morphometry
The research was supported in part by grants from the NIH, CIHR, and FRSQ. We would like to acknowledge the dedicated technical support from the Radiochemistry-Cyclotron and Positron Emission Tomography Units. M.D. is a Killam Scholar at the Montreal Neurological Institute, McGill University, C.B. holds a Chercheur National Award and M.L. holds a Chercheur Boursier from FRSQ. In addition, we would like to thank S. Milot and S.N. Young for their help and suggestions during this study.
- 2.Frazer A, Hensler J, Serotonin. In: Siegel G, Agranoff B, Albers R, Fisher S, Uhler M, eds. Basic neurochemistry, molecular, cellular, and medical sspects. 6th ed. Philadelphia: Lippincott, Williams & Wilkins, 1999.Google Scholar
- 9.Rabiner EA, Messa C, Sargent PA, Husted-Kjaer K, Montgomery A, Lawrence AD, et al. A database of [11C]WAY-100635 binding to 5-HT1A receptors in normal male volunteers: normative data and relationship to methodological, demographic, physiological, and behavioral variables. Neuroimage 2002;15:620–32.CrossRefPubMedGoogle Scholar
- 14.Diksic M, Tohyama Y, Takada A. Brain net unidirectional uptake of alpha-[14C]methyl-L-tryptophan (alpha-MTrp) and its correlation with regional serotonin synthesis, tryptophan incorporation into proteins, and permeability surface area products of tryptophan and alpha-MTrp. Neurochem Res 2000;25:1537–46.CrossRefPubMedGoogle Scholar
- 37.First M, Spitzer R, Gibbon M, Williams J. Structured clinical interview for the DSM–IV Axis I disorders (SCID I/P, Version 2.0). New York: Biometrics Research Department, New York State Psychiatric Institute, 1995.Google Scholar
- 38.Beck A, Beamesdefer A. Assessment of depression: the depression inventory. In: Pickot P, ed. Modern problems in psychopharmachology. Basel: S. Karger, 1974.Google Scholar
- 43.Collins D, Zijdenbos A, Barré W, Evans A. ANIMAL+INSECT: improved cortical structure segmentation. In: Kuba A SMaT-PA, ed. Proceedings of the Annual Symposium on Information Processing in Medical Imaging. Vol. 1613, 1999:210–23.Google Scholar
- 45.Zijdenbos A, Forghani R, Evans AC. Automatic quantification of MS lesions in 3D MRI brain data sets: validation of INSECT. Proceedings of the first International conference on medical image computing and computer-assisted intervention (MICCAI). Berlin: Springer, 1998.Google Scholar