Abstract
The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.
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- Annett M. A classification of hand preference by association analysis. Br J Psychol. 1970 Aug;61(3):303–321. doi: 10.1111/j.2044-8295.1970.tb01248.x. [DOI] [PubMed] [Google Scholar]
- Buckland P. R., O'Donovan M. C., McGuffin P. Changes in dopa decarboxylase mRNA but not tyrosine hydroxylase mRNA levels in rat brain following antipsychotic treatment. Psychopharmacology (Berl) 1992;108(1-2):98–102. doi: 10.1007/BF02245292. [DOI] [PubMed] [Google Scholar]
- Campbell I. C., Murphy D. L., Walker M. N., Lovenberg W., Robinson D. S. Monoamine oxidase inhibitors (MAOI) increase rat brain aromatic amino acid decarboxylase activity. Br J Clin Pharmacol. 1980 Apr;9(4):431–432. doi: 10.1111/j.1365-2125.1980.tb01073.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cepeda C., Buchwald N. A., Levine M. S. Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9576–9580. doi: 10.1073/pnas.90.20.9576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chouinard G., Jones B. D. Schizophrenia as dopamine-deficiency disease. Lancet. 1978 Jul 8;2(8080):99–100. doi: 10.1016/s0140-6736(78)91409-5. [DOI] [PubMed] [Google Scholar]
- Evans A. C., Marrett S., Neelin P., Collins L., Worsley K., Dai W., Milot S., Meyer E., Bub D. Anatomical mapping of functional activation in stereotactic coordinate space. Neuroimage. 1992 Aug;1(1):43–53. doi: 10.1016/1053-8119(92)90006-9. [DOI] [PubMed] [Google Scholar]
- Evans A. C., Marrett S., Torrescorzo J., Ku S., Collins L. MRI-PET correlation in three dimensions using a volume-of-interest (VOI) atlas. J Cereb Blood Flow Metab. 1991 Mar;11(2):A69–A78. doi: 10.1038/jcbfm.1991.40. [DOI] [PubMed] [Google Scholar]
- Garnett E. S., Firnau G., Nahmias C. Dopamine visualized in the basal ganglia of living man. Nature. 1983 Sep 8;305(5930):137–138. doi: 10.1038/305137a0. [DOI] [PubMed] [Google Scholar]
- Gjedde A., Léger G. C., Cumming P., Yasuhara Y., Evans A. C., Guttman M., Kuwabara H. Striatal L-dopa decarboxylase activity in Parkinson's disease in vivo: implications for the regulation of dopamine synthesis. J Neurochem. 1993 Oct;61(4):1538–1541. doi: 10.1111/j.1471-4159.1993.tb13651.x. [DOI] [PubMed] [Google Scholar]
- Gjedde A., Reith J., Dyve S., Léger G., Guttman M., Diksic M., Evans A., Kuwabara H. Dopa decarboxylase activity of the living human brain. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2721–2725. doi: 10.1073/pnas.88.7.2721. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grace A. A. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience. 1991;41(1):1–24. doi: 10.1016/0306-4522(91)90196-u. [DOI] [PubMed] [Google Scholar]
- Hadjiconstantinou M., Rossetti Z., Silvia C., Krajnc D., Neff N. H. Aromatic L-amino acid decarboxylase activity of the rat retina is modulated in vivo by environmental light. J Neurochem. 1988 Nov;51(5):1560–1564. doi: 10.1111/j.1471-4159.1988.tb01125.x. [DOI] [PubMed] [Google Scholar]
- Hadjiconstantinou M., Wemlinger T. A., Sylvia C. P., Hubble J. P., Neff N. H. Aromatic L-amino acid decarboxylase activity of mouse striatum is modulated via dopamine receptors. J Neurochem. 1993 Jun;60(6):2175–2180. doi: 10.1111/j.1471-4159.1993.tb03503.x. [DOI] [PubMed] [Google Scholar]
- Kay S. R., Fiszbein A., Opler L. A. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–276. doi: 10.1093/schbul/13.2.261. [DOI] [PubMed] [Google Scholar]
- Kuwabara H., Cumming P., Reith J., Léger G., Diksic M., Evans A. C., Gjedde A. Human striatal L-dopa decarboxylase activity estimated in vivo using 6-[18F]fluoro-dopa and positron emission tomography: error analysis and application to normal subjects. J Cereb Blood Flow Metab. 1993 Jan;13(1):43–56. doi: 10.1038/jcbfm.1993.7. [DOI] [PubMed] [Google Scholar]
- Le Van Thai A., Coste E., Allen J. M., Palmiter R. D., Weber M. J. Identification of a neuron-specific promoter of human aromatic L-amino acid decarboxylase gene. Brain Res Mol Brain Res. 1993 Mar;17(3-4):227–238. doi: 10.1016/0169-328x(93)90006-b. [DOI] [PubMed] [Google Scholar]
- Li X. M., Juorio A. V., Paterson I. A., Zhu M. Y., Boulton A. A. Specific irreversible monoamine oxidase B inhibitors stimulate gene expression of aromatic L-amino acid decarboxylase in PC12 cells. J Neurochem. 1992 Dec;59(6):2324–2327. doi: 10.1111/j.1471-4159.1992.tb10127.x. [DOI] [PubMed] [Google Scholar]
- MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., Barker J. L. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. 1986 May 29-Jun 4Nature. 321(6069):519–522. doi: 10.1038/321519a0. [DOI] [PubMed] [Google Scholar]
- Mackay A. V. Positive and negative schizophrenic symptoms and the role of dopamine. Br J Psychiatry. 1980 Oct;137:379–383. doi: 10.1192/bjp.137.4.379. [DOI] [PubMed] [Google Scholar]
- McGeorge A. J., Faull R. L. The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience. 1989;29(3):503–537. doi: 10.1016/0306-4522(89)90128-0. [DOI] [PubMed] [Google Scholar]
- Meltzer H. Y., Stahl S. M. The dopamine hypothesis of schizophrenia: a review. Schizophr Bull. 1976;2(1):19–76. doi: 10.1093/schbul/2.1.19. [DOI] [PubMed] [Google Scholar]
- Perez M. M., Trimble M. R. Epileptic psychosis--diagnostic comparison with process schizophrenia. Br J Psychiatry. 1980 Sep;137:245–249. doi: 10.1192/bjp.137.3.245. [DOI] [PubMed] [Google Scholar]
- Peters J. G. Dopamine, noradrenaline and serotonin spinal fluid metabolites in temporal lobe epileptic patients with schizophrenic symptomatology. Eur Neurol. 1979;18(1):15–18. doi: 10.1159/000115048. [DOI] [PubMed] [Google Scholar]
- Pycock C. J., Kerwin R. W., Carter C. J. Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats. Nature. 1980 Jul 3;286(5768):74–76. doi: 10.1038/286074a0. [DOI] [PubMed] [Google Scholar]
- Reith J., Dyve S., Kuwabara H., Guttman M., Diksic M., Gjedde A. Blood-brain transfer and metabolism of 6-[18F]fluoro-L-dopa in rat. J Cereb Blood Flow Metab. 1990 Sep;10(5):707–719. doi: 10.1038/jcbfm.1990.124. [DOI] [PubMed] [Google Scholar]
- Seeman P., Guan H. C., Van Tol H. H. Dopamine D4 receptors elevated in schizophrenia. Nature. 1993 Sep 30;365(6445):441–445. doi: 10.1038/365441a0. [DOI] [PubMed] [Google Scholar]
- Wong D. F., Wagner H. N., Jr, Tune L. E., Dannals R. F., Pearlson G. D., Links J. M., Tamminga C. A., Broussolle E. P., Ravert H. T., Wilson A. A. Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science. 1986 Dec 19;234(4783):1558–1563. doi: 10.1126/science.2878495. [DOI] [PubMed] [Google Scholar]
- Young E. A., Neff N. H., Hadjiconstantinou M. Evidence for cyclic AMP-mediated increase of aromatic L-amino acid decarboxylase activity in the striatum and midbrain. J Neurochem. 1993 Jun;60(6):2331–2333. doi: 10.1111/j.1471-4159.1993.tb03525.x. [DOI] [PubMed] [Google Scholar]
- Zhu M. Y., Juorio A. V., Paterson I. A., Boulton A. A. Regulation of aromatic L-amino acid decarboxylase by dopamine receptors in the rat brain. J Neurochem. 1992 Feb;58(2):636–641. doi: 10.1111/j.1471-4159.1992.tb09765.x. [DOI] [PubMed] [Google Scholar]