Abstract
The method for measuring serotonin synthesis in human brain uses [11C]α-methyl-L-tryptophan as a tracer and positron emission tomography. The α-methyl-L-tryptophan is converted to α-methylserotonin, which is not a substrate for monoamine oxidase and therefore accumulates in the brain. In a pilot study published recently, rates of serotonin synthesis were found to be higher in men than in women. This was due to the lower plasma free tryptophan in the women under the experimental conditions used, and does not necessarily reflect the situation in all circumstances. Acute tryptophan depletion lowered brain serotonin synthesis by 90% or more. Patients with borderline personality disorder, who exhibit emotional lability and impulsivity, may have lower brain serotonin synthesis rates than healthy controls.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ågren, H., Reibring, L., Hartvig, P., Tedroff, J., Bjurling, P., Hörnfeldt, K., Andersson, Y., Lundqvist, H., and Långström, B., 1991, Low brain uptake of L-[11C]5-hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers, Acta Psychiatr Scand. 83:449–455.
Anderson, I.M., Parry-Billings, M., Newsholme, E.A., Fairburn, C.G., and Cowen, P.J., 1990, Dieting reduces plasma tryptophan and alters brain 5-HT function in women, Psychol Med. 20:785–791.
Bremner, J.D., Innis, R.B., Salomon, R.M., Staib, L.H., Ng, C.K., Miller, H.L., Bronen, R.A., Krystal, J.H., Duncan, J., Rich, D., Price, L.H., Malison, R., Dey, H., Soufer, R., and Charney, D.S., 1997, Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse, Arch Gen Psychiatry. 54:364–374.
Brewerton, T.D., 1995, Toward a unified theory of serotonin dysregulation in eating and related disorders, Psychoneuroendocrinology. 20:561–590.
Chaly, T. and Diksic, M., 1988, Synthesis of “no-carrier-added” α-[11C]methyl-L-tryptophan, J Nucl Med. 29:370–374.
Cheetham, S.C., Crompton, M.R., Czudek, C., Horton, R.W., Katona, C.LE., and Reynolds, G.P, 1989, Serotonin concentrations and turnover in brains of depressed suicides, Brain Res. 502:332–340.
Chugani, D.C., Heyes, M.P., Kuhn, D.M., and Chugani, H.T., 1998a, Evidence α[C-11]methyl-L-tryptophan metabolism via the kynurenine pathway in tuberous sclerosis complex, Soc Neurosci Abstr. 24:1757.(Abstract).
Chugani, D.C., Muzik, O., Chakraborty, P., Mangner, T., and Chugani, H.T., 1998b, Human brain serotonin synthesis capacity measured in vivo with α-[C-11]methyl-L-tryptophan, Synapse. 28:33–43.
Cleare, A.J. and Bond, A.J., 1995, The effect of tryptophan depletion and enhancement on subjective and behavioural aggression in normal male subjects, Psychopharmacology. 118:72–81.
Cortés, R., Soriano, E., Pazos, A., Probst, A., and Palacios, J.M., 1988, Autoradiography of antidepressant binding sites in the human brain: Localization using [3H]imipramine and [3H]paroxetine, Neuroscience. 27:473–496.
Curzon, G., Friedel, J., Kantamaneni, B.D., Greenwood, M.H., and Lader, M.H., 1974, Unesterified fatty acids and the binding of tryptophan in human plasma, Clin Sci Mol Med. 47:415–424.
Dean, B., Hayes, W., Opeskin, K., Naylor, L., Pavey, G., Hill, C., Keks, N., and Copolov, D.L., 1995, Serotonin2 receptors and the serotonin transporter in the schizophrenic brain, Behav Brain Res. 73:169–175.
Delgado, P.L., Charney, D.S., Price, L.H., Aghajanian, G.K., Landis, H., and Heninger, G.R., 1990, Serotonin function and the mechanism of antidepressant action: reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan, Arch Gen Psychiatry. 47:411–418.
Diksic, M., Nagahiro, S., Sourkes, T.L., and Yamamoto, Y.L., 1990, A new method to measure brain serotonin synthesis in vivo. I. Theory and basic data for a biological model, J Cereb Blood Flow Metab. 10:1–12.
Ellenbogen, M.A., Young, S.N., Dean, P., Palmour, R.M., and Benkelfat, C., 1996, Mood response to acute tryptophan depletion in healthy volunteers: Sex differences and temporal stability, Neuropsychopharmacology. 15:465–474.
Garelis, E., Young, S.N., Lal, S., and Sourkes, T.L., 1974, Monoamine metabolites in lumbar CSF: their sites of origin in relation to clinical studies, Brain Res. 79:1–8.
Heninger, G.R., 1995, Indoleamines: The role of serotonin in clinical disorders, in: Psychopharmacology: The Fourth Generation of Progress, F.E. Bloom and D.J. Kupfer, eds., pp. 471–482, Raven Press, New York.
Heninger, G.R., 1997, Serotonin, sex, and psychiatric illness, Proc Natl Acad Sci USA. 94:4823–4824.
Heyes, M.P., Saito, K., Crowley, J.S., Davis, L.E., Demitrack, M.A., Der, M., Dilling, L.A., Elia, J., Kruesi, M.J.P., Lackner, A., Larsen, S.A., Lee, K., Leonard, H.L., Markey, S.P., Martin, A., Milstein, S., Mouradian, M.M., Pranzatelli, M.R., Quearry, B.J., Salazar, A., Smith, M., Strauss, S.E., Sunderland, T., Swedo, S.W., and Tourtellotte, W.W., 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease, Brain. 115:1249–1273.
Joyce, J.N., Shane, A., Lexow, N., Winokur, A., Casanova, M.F., and Kleinman, J.E., 1993, Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics, Neuropsy-chopharmacology. 8:315–336.
Kalkner, K.M., Nilsson, S., Bergstrm, M., Lindner, K.J., Westerberg, G., Longstrm, B., and Westlin, J.E., 1997, PET with hydroxytryptophan as tracer in hormone-refractory prostatic adenocarcinoma: evaluation of decarboxylation in vivo, In Vivo. 11:377–381.
Kennett, G.A., Chaouloff, F., Marcou, M., and Curzon, G., 1986, Female rats are more vulnerable than males in an animal model of depression: the possible role of serotonin, Brain Res. 382:416–421.
Laruelle, M., Vanisberg, M.A., and Maloteaux, J.M., 1988, Regional and subcellular localization in human brain of [3H]paroxetine binding, a marker of serotonin uptake sites, Biol Psychiatry. 24:299–309.
Madras, B.K. and Sourkes, T.L., 1965, Metabolism of a-methyltryptophan, Biochem Pharmacol. 14:1499–1506.
Missala, K. and Sourkes, T.L., 1988, Functional cerebral activity of an analogue of serotonin formed in situ, Neurochem Int. 12:209–214.
Moeller, F.G., Dougherty, D.M., Swann, A.C., Collins, D., Davis, C.M., and Cherek, D.R., 1996, Tryptophan depletion and aggressive responding in healthy males, Psychopharmacology. 126:97–103.
Nagahiro, S., Diksic, M., Yamamoto, Y.L., and Riml, H., 1990a, Non-invasive in-vivo autoradiographic method to measure axonal transport in serotoninergic neurons in the rat brain, Brain Res. 506:120–128.
Nagahiro, S., Takada, A., Diksic, M., Sourkes, T.L., Missala, K., and Yamamoto, Y.L., 1990b, A new method to measure brain serotonin synthesis in vivo. II. A practical autoradiographic method tested in normal and lithium-treated rats, J Cereb Blood Flow Metab. 10:13–21.
Neumeister, A., Praschak-Rieder, N., Hesselmann, B., Tauscher, J., and Kasper, S., 1997, The tryptophan depletion test: Basic principles and clinical relevance, Nervenarzt. 68:556–562.
Nishizawa, S., Benkelfat, C., Young, S.N., Leyton, M., Mzengeza, S., de Montigny, C., Blier, P., and Diksic, M., 1997, Differences between males and females in rates of serotonin synthesis in human brain, Proc Natl Acad Sci USA. 94:5308–5313.
Okazawa, H., Leyton, M., Diksic, M., Sookman, D., Blier, P., Paris, J., and Benkelfat, C., 1998, Regional rates of brain serotonin synthesis in patients with borderline personality disorder vs obsessive-compulsive disorder: Analyses with statistical parametric mapping, Neuroimage. 7:233.(Abstract).
Patlak, C.S. and Blasberg, R.G., 1985, Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data: Generalizations, J Cereb Blood Flow Metab. 5:584–590.
Pihl, R.O., Young, S.N., Harden, P., Plotnick, S., Chamberlain, B., and Ervin, F.R., 1995, Acute effect of altered tryptophan levels and alcohol on aggression in normal human males, Psychopharmacology. 119:353–360.
Reilly, J.G., McTavish, S.F., and Young, A.H., 1997, Rapid depletion of plasma tryptophan: A review of studies and experimental methodology, J Psychopharmacol. 11:381–392.
Shoaf, S.E. and Schmall, B., 1996, Pharmacokinetics of α-methyl-L-tryptophan in rhesus monkeys and calculation of the lumped constant for estimating the rate of serotonin synthesis, J Pharmacol Exp Ther. 277:219–224.
Shoaf, S.E., Carson, R., Hommer, D., Williams, W., Higley, J.D., Schmall, B., Herscovitch, P., Eckelman, W., and Linnoila, M., 1998, Brain serotonin synthesis rates in rhesus monkeys determined by [11C]α-methyl-L-tryptophan and positron emission tomography compared to CSF 5-hydroxyindole-3-acetic acid concentrations, Neuropsychopharmacology. 19:345–353.
Sokoloff, L., Reivich, M., Kennedy, C., Des Rosiers, M.H., Patlak, C.S., Pettigrew, K.D., Sakurada, O., and Shinohara, M., 1977, The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat, J Neurochem. 28:897–916.
Sourkes, T.L., 1971, Alpha-methyltryptophan and its actions on tryptophan metabolism, Federation Proc. 30:897–903.
van Praag, H.M., 1994, Anxiety and aggression as pacemakers of depression: A dimensional variation of the serotonin hypothesis of depression, in: Current Therapeutic Approaches to Panic and Other Anxiety Disorders, J. Mendlewicz, G. Racagni, and N. Brunello, eds., pp. 144–150, Karger, Basel.
Vanier, M., Tsuiki, K., Grdisa, M., Worsley, K., and Diksic, M., 1995, Determination of the lumped constant for the alpha-methyltryptophan method of estimating the rate of serotonin synthesis, J Neurochem. 64:624–635.
Young, L.T., Warsh, J.J., Kish, S.J., Shannak, K., and Hornykiewicz, O., 1994, Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder, Biol Psychiatry. 35:121–127.
Young, S.N., Smith, S.E., Pihl, R.O., and Ervin, F.R., 1985, Tryptophan depletion causes a rapid lowering of mood in normal males, Psychopharmacology. 87:173–177.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Young, S.N., Leyton, M., Benkelfat, C. (1999). Pet Studies of Serotonin Synthesis in the Human Brain. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_2
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4709-9_2
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7133-5
Online ISBN: 978-1-4615-4709-9
eBook Packages: Springer Book Archive