Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-19T05:50:50.407Z Has data issue: false hasContentIssue false

Plasma Amino Acids in Relation to Cerebrospinal Fluid Monoamine Metabolites in Schizophrenic Patients and Healthy Controls

Published online by Cambridge University Press:  29 January 2018

Lars Bjerkenstedt*
Affiliation:
Department of Psychiatry and Psychology, Karolinska Institute, PO Box 60500, S-104 01 Stockholm, Sweden
Gunnar Edman
Affiliation:
Department of Psychiatry and Psychology, Karolinska Institute, PO Box 60500, S-104 01 Stockholm, Sweden
Lars Hagenfeldt
Affiliation:
Department of Clinical Chemistry, Karolinska Institute, PO Box 60500, S-104 01 Stockholm, Sweden
Göran Sedvall
Affiliation:
Department of Psychiatry and Psychology, Karolinska Institute, PO Box 60500, S-104 01 Stockholm, Sweden
Frits-Axel Wiesel
Affiliation:
Department of Psychiatry and Psychology, Karolinska Institute, PO Box 60500, S-104 01 Stockholm, Sweden
*
Correspondence.

Summary

Compared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids. In the patients, homovanillic (HVA) acid levels in CSF were decreased and the plasma levels of the amino acids competing with tyrosine and tryptophan for transport into the brain, were all negatively correlated to the CSF concentrations of HVA and 5-HIAA. These findings could be explained by a change in the affinity of the L-system or by a decrease in its overall capacity in schizophrenia. Raised plasma levels of the competing amino acids may limit the brain uptake of tyrosine, leading to a diminished dopamine turnover, and resulting in a compensatory development of supersensitive dopamine receptors.

Type
Papers
Copyright
Copyright © 1985 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Åsberg, M., Perris, C., Schalung, D. & Sedvall, G. (1978) The CPRS – Development and applications of a psychiatric rating scale. Acta Psychiatrica Scandinavica, Suppl. 271.Google Scholar
Ashcroft, G. W., Crawford, T. B. B. Eccleston, D. F., Macdougall, E. J., Stanton, J. B. & Binns, J. K. (1966) 5-hydroxyindole compounds in the cerebrospinal fluid of patients with psychiatric or neurological diseases. Lancet, ii, 10491050.CrossRefGoogle Scholar
Berger, P. A., Faull, K. F., Kilkowski, J., Anderson, P. J., Kraemer, H., Davis, K. L. & Barchas, J. D. (1980) CSF monoamine metabolites in depression and schizophrenia. American Journal of Psychiatry, 137, 174180.Google ScholarPubMed
Bjerkenstedt, L., Gullberg, B., Härnryd, C. & Sedvall, G. (1977) Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with melperone and thiothixene. Archive für Psychiatrie und Nervenkrankheiten, 224, 107118.CrossRefGoogle ScholarPubMed
Bjerkenstedt, L., Härnryd, C., Grimm, V., Gullberg, B. & Sedvall, G. (1978) A double blind comparison of melperone and thiotixene in psychotic women using a new rating scale, the CPRS. Archive für Psychiatrie und Nervenkrankheiten, 226, 157172.CrossRefGoogle Scholar
Bliss, C. I. (1967) Statistics is Biology. New York: McGraw-Hill.Google Scholar
Bowers, M. B. Jr. (1974) Central dopamine turnover in schizophrenic syndromes. Archives of General Psychiatry, 31, 5054.CrossRefGoogle ScholarPubMed
Carlsson, A. & Lindqvist, M. (1963) Effects of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica, 20, 140144.CrossRefGoogle ScholarPubMed
Crow, T. J., Owen, F., Cross, A. J., Ferrier, I. N., Johnstone, E. C., McCreadie, R. G., Owens, D. G. C. & Poulter, M. (1981) Neurotransmitter enzymes and receptors in post-mortem brain; evidence that an increase in D, dopamine receptors is associated with the Type I syndrome. E In: Transmitter Biochemistry of Human Brain Tissue, (eds. Usdin, E. & Rièderer, P.). London: MacMillan.Google Scholar
Crow, T. J. (1983) Increases in striatal D2 Dopamine receptors and decrease in cholecystokinin and somatostatin in temporal lobe in relation to the types I and II syndrome in schizophrenia. Abstract No S 451, VII World Congress of Psychiatry, Vienna.Google Scholar
Fernstrom, J. D. & Wurtman, R. J. (1972) Brain serotonin content: Psychological regulation by plasma neutral amino acids. Science, 178, 414416.CrossRefGoogle Scholar
Fernstrom, J. D. & Faller, D. V. (1978) Neutral amino acids in the brain: Changes in response to food ingestion. Journal of Neurochemistry, 30, 15311538.CrossRefGoogle ScholarPubMed
Hagenfeldt, L., Bjerkenstedt, L., Edman, G., Sedvall, G. & Wiesel, F. A. (1983a) Amino acids and monoamine metabolites in cerebrospinal fluid—interrelationships in healthy subjects. Journal of Neurochemistry, 42, 833837.CrossRefGoogle Scholar
Hagenfeldt, L., Eriksson, L. S. & Wahren, J. (1983b) Amino acids in liver disease. Proceedings of the Nutrition Society, 42, 497506.CrossRefGoogle ScholarPubMed
Van Kammen, D. P. Mann, L. S., Sternberg, D. E., Scheinen, M., Marder, S. R., Rieder, R. O. & Linnoila, M. (1983) Spinal fluid dopamine betahydroxylase activity and homovanillic acid levels in schizophrenic patients with brain atrophy. Science, 220, 974977.CrossRefGoogle Scholar
Kim, J. S., Kornhuver, H. H., Schmid-Burgk, W. & Holzmiller, B. (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neuroscience Letters, 20, 379382.CrossRefGoogle Scholar
Kopin, I. J., Gordon, E. K., Jimerson, D. C. & Pounsky, R. J. (1983) Relation between plasma and cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol. Science, 219, 7376.CrossRefGoogle ScholarPubMed
Lorenzo, A. V. (1974) Amino acid transport mechanisms of the cerebrospinal fluid. Federation Proceedings, 33, 10791085.Google ScholarPubMed
Mackay, A. V. P., Iversen, L. L., Rossor, M., Spokes, E., Bird, E., Arregut, A., Creese, I. & Snyder, S. H. (1981) Increased brain dopamine and dopamine receptors in schizophrenia In Biological Psychiatry: Developments in Psychiatry (eds. Perris, C., Struwe, G. & Jansson, B.). Amsterdam: Elsevier/North-Holland.Google Scholar
McKean, C. M. (1972) The effects of high phenylalanine concentrations on serotonin and catecholamine metabolism in the human brain. Brain Research, 47, 469472.CrossRefGoogle ScholarPubMed
Moore, K. E. & Thornburg, J. E. (1975) Drug-induced dopaminergic supersensitivity. Advances in Neurology, 9, 93103.Google ScholarPubMed
Munkvad, J. (1951) Glutaminesyre-og Glutaminbestemmelser i plasma. Doctoral Thesis. Köpenhamn: Arne Frost-Hansens Forlag.Google Scholar
Nordin, C., Siwers, B. & Bertilsson, L. (1982) Site of lumbar puncture influences levels of monoamine metabolites. Archives of General Psychiatry, 39, 1445.CrossRefGoogle ScholarPubMed
Nybäck, H., Berggren, B. M., Hindmarsh, T., Sedvall, G. & Wiesel, F. A. (1983) Cerebroventricular size and cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy volunteers. Psychiatric Research, 9, 301308.CrossRefGoogle ScholarPubMed
Owen, F., Cross, A. J., Crow, T. J., Longden, A., Poulter, M. & Riley, G. J. (1978) Increased dopamine receptor sensitivity in schizophrenia. Lancet, ii, 223225.CrossRefGoogle Scholar
Owen, F., Cross, A. J., Crow, T. J., Poulter, M. & Waddington, J. L. (1981) Increased dopamine receptors in schizophrenia: Specificity and relationship to drugs and symptomatology In Biological Psychiatry: Developments in Psychiatry (eds. Perris, C., Struwe, G. & Jansson, B.). Amsterdam: Elsevier/North-Hoiland.Google Scholar
Pardridge, W. M. & Oldendorf, W. H. (1977) Transport of metabolic substrates through the blood-brain barrier. Journal of Neurochemistry, 28, 512.CrossRefGoogle ScholarPubMed
Persson, T. & Roos, B. E. (1969) Acid metabolites from monoamine in cerebrospinal fluid of chronic schizophrenics. British Journal of Psychiatry, 115, 9598.CrossRefGoogle ScholarPubMed
Poisner, A. (1960) Serum phenylalanine in schizophrenia: Biochemical genetic aspects. Journal of Nervous and Mental Disease, 131, 7476.CrossRefGoogle ScholarPubMed
Post, R. M., Fink, E., Carpenter, W. T. & Goodwin, F. K. (1975) Cerebrospinal fluid amine metabolites in acute schizophrenia. Archives of General Psychiatry, 32, 10631069.CrossRefGoogle ScholarPubMed
Randrup, A. & Munkvad, I. (1967) Brain dopamine and the amphetamine-reserpine interaction. Journal of Pharmacy and Pharmacology, 19, 483484.CrossRefGoogle ScholarPubMed
Reveley, M. A., De Belleroche, J., Recordati, A. & Hirsch, S. R. (1983) Increased CSF amino acids and ventricular enlargement in schizophrenia. Abstract No. 245, VII World Congress of Psychiatry, Vienna.Google Scholar
van Rossum, J. M. (1966) The significance of dopamine receptor blockade for the mechanism of action of neuroleptic drugs. Archives Internationales de Pharmacodynamie et de Therapie, 160, 492494.Google ScholarPubMed
Sato, Y., Eriksson, S., Hagenfeldt, L. & Wahren, J. (1981) Influence of branched chain amino acids infusion on arterial concentrations and brain exchange of amino acids in patients with hepatic cirrhosis. Clinical Physiology, 1, 151165.CrossRefGoogle Scholar
Sedvall, G. & Wode-Helgodt, B. (1980) Aberrant monoamine metabolite levels in CSF and family history of schizophrenia. Archives of General Psychiatry, 37, 11131116.CrossRefGoogle ScholarPubMed
Staunton, D. A., Magistretti, P. J., Koob, G. F., Shoemaker, W. J. & Bloom, F. E. (1982) Dopaminergic supersensitivity induced by denervation and chronic receptor blockade is additive. Nature, 299, 7274.CrossRefGoogle ScholarPubMed
Spitzer, R., Endicott, J. & Robins, E. (1977) Diagnostic Criteria I. Schizophrenia. Research Diagnostic Criteria (RDC) for a selected group of functional disorders. Biometric Research. New York: New York State Psychiatric Institute.Google Scholar
Swahn, C.-G., Sandgärde, B., Wiesel, F.-A. & Sedvall, G. (1976) Simultaneous determination of the three major monoamine metabolites in brain tissue and body fluids by a mass fragmentographic method. Psychopharmacology, 48, 147152.CrossRefGoogle Scholar
Ungerstedt, R., Liungberg, T., Hoffer, B. & Siggins, G. (1975) Dopaminergic supersensitivity in the striatum. Advances in Neurology, 9, 5765.Google ScholarPubMed
Wahren, J., Hagenfeldt, L. & Felig, P. (1975) Splanchnic and leg exchanges of glucose, amino acids and free fatty acids during exercise in diabetes mellitus. Journal of Clinical Investigations, 55, 13031314.CrossRefGoogle ScholarPubMed
Wiesel, F.-A., Bjerkenstedt, L., Herlofsson, J., Härnryd, C., Nybäck, H., Oxenstierna, G. & Sedvall, G. (1984) Psychiatric morbidity with the family and steady state levels of CSF monoamine metabolites. In Neurology and Neurobiology. Volume 8C (eds. Usdin, E., Carlsson, A., Dahlström, A. & Engel, J.). New York: Alan R. Liss.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.