Hostname: page-component-745bb68f8f-v2bm5 Total loading time: 0 Render date: 2025-01-09T01:03:36.890Z Has data issue: false hasContentIssue false
  • English
  • Français

Proton magnetic resonance spectroscopy: an in vivo method of estimating hippocampal neuronal depletion in schizophrenia

Published online by Cambridge University Press:  09 July 2009

M. Maier ,
M. A. Ron ,
G. J. Barker  and
P. S. Tofts
M. Maier*
Affiliation:
Institute of Neurology, Queen Square, London
M. A. Ron
Affiliation:
Institute of Neurology, Queen Square, London
G. J. Barker
Affiliation:
Institute of Neurology, Queen Square, London
P. S. Tofts
Affiliation:
Institute of Neurology, Queen Square, London
*
1Address for correspondence: Dr M. Maier, Institute of Neurology, Queen Square, London WC1N 3BG.
Get access Rights & Permissions [Opens in a new window]

Synopsis

Diffuse loss of cortical volume and ventricular enlargement have been demonstrated in schizophrenia using imaging. In addition, histological studies have provided evidence that the number of neurons in the medial temporal lobe structures is reduced and that the cytoarchitecture is abnormal. In an attempt to correlate these histological findings with in vivo estimates of neuronal integrity we have studied the concentration of the neuronal marker N-acetyl aspartate (NAA) in the hippocampi of schizophrenics using in vivo Magnetic Resonance Spectroscopy (MRS). Compared with a group of healthy volunteers schizophrenics showed a 22% loss of NAA in the left hippocampus. Two other metabolites, choline and creatine showed bilateral reduction in schizophrenics and these achieved significance in the left hippocampus. These results indicate a significant depletion of NAA in schizophrenia and are in close agreement with the reported neuronal loss in the hippocampus detected histologically. We propose that in vivo MRS is a valid measure of integrity of neuronal populations in schizophrenia.

Type
Original Articles
Information
Psychological Medicine , Volume 25 , Issue 6 , November 1995 , pp. 1201 - 1209
Copyright
Copyright © Cambridge University Press 1995

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

REFERENCES

Altshuler, L. L. (1987). Hippocampal pyramidal cell orientation in schizophrenia. Archives of General Psychiatry 44, 1094–1098.CrossRefGoogle ScholarPubMed
Arnold, D. L. (1992). Reversible reduction of NAA after acute central nervous system damage. Society of Magnetic Resonance in Medicine (Book of Abstracts) 1, 643.Google Scholar
Arnold, D. L., Mathews, P. M., Francis, G. & Antel, J. (1990). Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of the disease. Magnetic Resonance in Medicine 14, 154–159.CrossRefGoogle Scholar
Austin, S. J., Connelly, A., Gadian, D. G., Benton, J. S. & Brett, E. M. (1991). Localized 1[H]NMR spectroscopy in Canavan's Disease: a report of two cases. Magnetic Resonance in Medicine 19, 439–445.CrossRefGoogle Scholar
Birken, D. L. & Oldendorf, W. H. (1989). N-acetyl-1-aspartic acid: a literature review of a compound prominent in 1[H]-NMR spectroscopic studies of brain. Neuroscience and Behavioural Reviews 13, 23–31.CrossRefGoogle Scholar
Bogerts, B., Ashtari, M., DeGreef, G., Alvir, J.-M. S., Bilder, R. M. & Lieberman, J. A. (1990). Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiatry Research 35, 1–13.CrossRefGoogle ScholarPubMed
Breiter, S. N., Arroyo, S., Mathews, V. P., Lesser, R. P., Bryan, R. N. & Barker, P. B. (1994). Proton MR spectroscopy in patients with seizure disorders. American Journal of Neuroradiology 15, 373–384.Google ScholarPubMed
Brenner, R. E., Beech, J. S., Williams, S. C. R., Bell, J. D. & McDonald, W. I. (1993). Reversibility of the reduction of NAA in diabetic ketoacidosis. Society of Magnetic Resonance in Medicine (Book of Abstracts) 3, 1559.Google Scholar
Brown, R., Colter, N., Corsellis, J. A. N., Crow, T. J., Frith, C. D., Jagoe, R., Johnstone, E. C. & Marsh, L. (1986). Postmortem evidence of structural brain changes in schizophrenia. Archives of General Psychiatry 43, 36–42.CrossRefGoogle ScholarPubMed
Bruhn, H., Frahm, J., Gyngell, M. L., Merboldt, K. D., Haenicke, W. & Sauter, R. (1989). Cerebral metabolism in man after acute stroke: new observations using localized proton NMR spectroscopy. Magnetic Resonance in Medicine 9, 126–131.CrossRefGoogle ScholarPubMed
Bruhn, H., Weber, T., Thorwirth, V. & Frahm, J. (1991). In vivo monitoring of neuronal loss in Creutzfeldt-Jakob disease by proton magnetic resonance spectroscopy. Lancet 337, 1610–1611.CrossRefGoogle ScholarPubMed
Buckley, P., Moore, C., Larkin, C., Mulvany, F., Redmond, O., Stack, J. P., Ennis, J. T. & Waddington, J. L. (1993). 1[H] magnetic resonance spectroscopy of frontal and temporal lobe metabolism in schizophrenia. Schizophrenia Bulletin (Special Issue) p. 194.Google Scholar
Calabrese, G., Deicken, R. F., Feine, G., Merrin, E. L., Schoenfeld, F. & Weiner, M. W. (1992). 31-Phosphorous magnetic resonance spectroscopy of the temporal lobes in schizophrenia. Biological Psychiatry 32, 26–32.CrossRefGoogle Scholar
Chi, J. G., Dooling, E. C. & Gilles, F. H. (1977). Gyral development of the human brain. Annals of Neurology 1, 86–93.CrossRefGoogle ScholarPubMed
Chong, W. K., Sweeney, B., Wilkinson, I. D., Paley, M., Hall-Craggs, M. A., Kendall, B. E., Shepard, J. K., Beecham, M., Miller, R. F., Weller, I. V. D., Newman, S. P. & Harrison, M. J. (1993). Proton spectroscopy of the brain in HIV infection: correlation with clinical immunologic and MR imaging findings. Radiology 188, 119–124.CrossRefGoogle ScholarPubMed
Conrad, A. J., Abebe, T., Austin, R., Forsythe, S. & Scheibel, A. B. (1991). Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Archives of General Psychiatry 48, 413–417.CrossRefGoogle ScholarPubMed
Davie, C. A., Hawkins, C. P., Barker, G. J., Brennan, A., Tofts, P. S., Miller, D. H. & McDonald, W. I. (1994). Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 117, 49–58.CrossRefGoogle ScholarPubMed
De Stefano, N., Francis, G., Antel, J. P. & Arnold, D. L. (1993). Reversible decreases of NAA in the brain of patients with replacing remitting multiple sclerosis. Society of Magnetic Resonance in Medicine (Book of Abstracts) 1, 280.Google Scholar
DeCarli, C., Murphy, D. G. M., Gillette, J. A., Haxby, J. V., Teichberg, D., Schapiro, M. B. & Horwitz, B. (1994). Lack of age-related differences in temporal lobe volume of very healthy adults. American Journal of Neuroradiology 15, 689–696.Google ScholarPubMed
Demisch, L., Gerbaldo, H., Heinz, K. & Kirsten, R. (1987). Transmembranal signalling in schizophrenic and affective disorders: studies on arachidonic acid and phospholipids. Schizophrenia Research 22, 275–282.Google Scholar
Espanol, M. T., Yang, G. Y., Shimizu, H., Xu, Y., Chang, L. H., Weinstein, P., Litt, L. & James, T. L. (1992). Does NAA predict outcome of transient global cerebral ischaemia in rat brain? Society of Magnetic Resonance in Medicine (Book of Abstracts) 2, 2148.Google Scholar
Falkai, P. & Bogerts, B. (1986). Cell loss in the hippocampus of schizophrenics. European Archives of Psychiatry and Neurological Sciences 236, 154–161.CrossRefGoogle ScholarPubMed
Fisher, M., Sotak, C. H., Minematsu, K. & Li, L. (1992). New magnetic resonance techniques for evaluating cerebrovascular disease. Annals of Neurology 32, 115–122.CrossRefGoogle ScholarPubMed
Frahm, J., Bruhn, H., Glyngell, M. L., Merboldt, K. D., Hanicke, W. & Sauter, R. (1989 a). Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magnetic Resonance in Medicine 9, 79–93.CrossRefGoogle ScholarPubMed
Frahm, J., Bruhn, H., Gyngell, M. L., Merboldt, K. D., Haenicke, W. & Sauter, R. (1989 b). Localized proton NMR spectroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites. Magnetic Resonance in Medicine 11, 47–63.CrossRefGoogle ScholarPubMed
Frahm, J., Michaelis, T., Merboldt, K. D., Bruhn, H., Gyngell, M. L. & Hanicke, W. (1990). Improvements in localized proton NMR spectroscopy of human brain: water suppression, short echo times, and 1 ml resolution. Journal of Magnetic Resonance 90, 464–473.Google Scholar
Gattaz, W. F., Kolisch, M., Thuren, T., Virtanen, J. A. & Kinnunen, P. K. J. (1987). Increased plasma phospholipase A2 activity in schizophrenic patients: reduction after neuroleptic therapy. Biological Psychiatry 22, 421–426.CrossRefGoogle ScholarPubMed
Gill, S. S., Thomas, D. G. T., Van Bruggen, N., Gadian, D. G., Peden, C. J., Bell, J. D., Cox, J., Menon, D. K., Iles, R. A., Bryant, D.J. & Coutts, G. A. (1990). Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies. Journal of Computer Assisted Tomography 14, 497–504.CrossRefGoogle ScholarPubMed
Graham, S. H., Meyerhoff, D. J., Bayne, L., Sharp, F. R. & Weiner, M. W. (1994). Magnetic resonance spectroscopy of N-acetyl aspartate in hypoxic-ischaemic encephalopathy. Annals of Neurology 35, 490–494.CrossRefGoogle Scholar
Grodd, W., Kraegeloh-Mann, I., Peterson, D., Trefz, F. K. & Harzer, K. (1990). In vivo assessment of N-acetyl aspartate in brain in spongy degeneration (Canavan's disease) by proton spectroscopy. Lancet 336, 437–438.CrossRefGoogle ScholarPubMed
Harvey, I., Ron, M. A., Du Boulay, G., Wicks, D., Lewis, S. W. & Murray, R. M. (1993). Reduction of cortical volume in schizophrenia on magnetic resonance imaging. Psychological Medicine 23, 591–604.CrossRefGoogle ScholarPubMed
Hechers, S., Heinsen, H., Geiger, B. & Beckmann, H. (1991). Hippocampal Neuronal Number in Schizophrenia. Archives of General Psychiatry 48, 1002–1008.CrossRefGoogle Scholar
Hitzemann, R., Hirschowitz, D. & Garver, D. (1984). Membrane abnormalities in the psychoses and affective disorders. Journal of Psychiatric Research 18, 319–326.CrossRefGoogle ScholarPubMed
Inglis, B. A., Brenner, R. E., Munro, P. M. G., Williams, S. C. R., McDonald, W. I. & Sales, K. D. (1992). Measurement of proton NMR relaxation times for NAA, Cr and Cho in acute EAE. Society of Magnetic Resonance in Medicine (Book of Abstracts) 2, 2162.Google Scholar
Kaiya, H., Takeuchi, K., Namba, M., Imcu, A., Nakashima, S. & Nozawa, Y. (1984). Abnormal phosphatidylinositol-cycle of platelet membrane in schizophrenia: A preliminary study. Folia Psychiatrica et Neurologica Japonica 38, 437–444.Google ScholarPubMed
Koller, K. J., Zaczek, R, & Coyle, J. T. (1984). N-acetyl-aspartyl-glutamate: regional levels in rat brain and the effects of brain lesions as determined by a new HPLC method. Journal of Neurochemistry 43, 1136–1142.CrossRefGoogle ScholarPubMed
Marsh, L., Suddath, R. L., Higgins, N. & Weinberger, D. R. (1994). Medial temporal lobe structures in schizophrenia: relationship of size to duration of illness. Schizophrenia Research 11, 225–238.CrossRefGoogle ScholarPubMed
Michaelis, T., Merboldt, K. D., Bruhn, H., Haenicke, W. & Frahm, J. (1993). Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. Radiology 187, 219–227.CrossRefGoogle ScholarPubMed
Miller, B L. (1991). A review of chemical issues in 1[H]NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR in Biomedicine 4, 47–52.CrossRefGoogle Scholar
Miller, D. H., Austin, S. J., Connelly, A., Youl, B. D., Gadian, D. G. & McDonald, W. I. (1991). Proton magnetic resonance spectroscopy of an acute and chronic lesion in multiple sclerosis. Lancet 337, 58–59.CrossRefGoogle ScholarPubMed
Moore, C. M., Redmond, O. M., Buckley, P., Larkin, C., Stack, J. P., Waddington, J. & Ennis, J. T. (1992). In vivo proton NMR spectroscopy (STEAM) in patients with schizophrenia. Society of Magnetic Resonance in Medicine (Book of Abstracts) 1, 1933.Google Scholar
Nasrallah, H. A., Skinner, T. E., Schmalbrock, P. & Robitaille, P. M. (1992). In vivo proton magnetic resonance spectroscopy (MRS) of the hippocampus/amygdala region in schizophrenia. Schizophrenia Bulletin (Special Issue) p. 150.Google Scholar
Okumura, N., Otsuki, S. & Nasu, H. (1959). The influence of insulin hypoglycaemic coma, repeated electroshocks, and chlorpromazine or beta-phenylisopropylmethylamine administration on the free amino acids in the brain. Journal of Biochemistry 46, 247–252.CrossRefGoogle Scholar
Pangerl, A. M., Steudle, A., Jaroni, H. W., Rufer, R. & Gattaz, W. F. (1991). Increased platelet membrane lysophosphatidylcholine in schizophrenia. Biological Psychiatry 8, 837–840.CrossRefGoogle Scholar
Pettegrew, J. W., Withers, G., Panchalingam, K. & Post, J. F. M. (1987). 31[P]Nuclear magnetic resonance (NMR) spectroscopy of brain in aging and Altheimer's disease. Journal of Neural Transmission 24, (Supplement), 261–268.Google Scholar
Pettegrew, J. W., Moossy, J., Withers, G., McKeag, D. & Panchalingam, K. (1988). 31[P]Nuclear magnetic resonance study of the brain in Alzheimer's disease. Journal of Neuropathology and Experimental Neurology 47, 235–248.CrossRefGoogle Scholar
Roberts, G. W. (1991). Schizophrenia: a neuropathological perspective. British Journal of Psychiatry 158, 8–17.CrossRefGoogle ScholarPubMed
Scheibel, A. B. & Conrad, A. S. (1993). Hippocampal dysgenesis in mutant mouse and schizophrenic man: is there a relationship? Schizophrenia Bulletin 19, 21–33.CrossRefGoogle Scholar
Sharma, R., Venkatasubramanian, P. N., Barany, M. & Davis, J. M. (1992). Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients. Schizophrenia Research 8, 43–49.CrossRefGoogle ScholarPubMed
Steudle, A., Maras, A. & Gattaz, W. F. (1994). Platelet membrane phospholipids in schizophrenia. Schizophrenia Research 11, 123.Google Scholar
Stevens, J. D. (1972). The distribution of phospholipid fractions in the red cell membranes of schizophrenics. Schizophrenia Bulletin 6, 60–61.CrossRefGoogle Scholar
Suddath, R. L., Casanova, M. F., Goldberg, T. E., Daniel, D. G., Kelsoe, J. R. & Weinberger, D. R. (1989). Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. American Journal of Psychiatry 146, 464–472.Google ScholarPubMed
Tews, J. K., Carter, S. H., Roa, P. D. & Stone, W. E. (1963). Free amino acids and related compounds in dog brain: post-mortem and anoxic changes, effects of ammonium chloride infusion, and levels during seizures induced by picrotoxin and by pentylenetetrazol. Journal of Neurochemistry 10, 641–653.CrossRefGoogle ScholarPubMed
Toft, P. B., Christiansen, P., Pryds, O., Lou, H. C. & Henriksen, O. (1994). T1, T2, and concentrations of brain metabolites in neonates and adolescents estimated with H-1 MR spectroscopy. Journal of Magnetic Resonance Imaging 4, 1–5.CrossRefGoogle ScholarPubMed
Waddington, J. L. (1993). Schizophrenia: developmental neuroscience and pathobiology. Lancet 341, 531–536.CrossRefGoogle ScholarPubMed
Yurgelun-Todd, D. A., Renshaw, P. F., Waternaux, S. A., Gruber, S. A. & Cohen, B. M. (1993). 1H spectroscopy of the temporal lobes in schizophrenic and bipolar patients. Society of Magnetic Resonance in Medicine (Book of Abstracts) 3, 1539.Google Scholar
Zipursky, R. B., Lim, K. O., Sullivan, E. V., Brown, B. W. & Pfefferbaum, A. (1992). Widespread cerebral grey matter volume deficits in schizophrenia. Archives of General Psychiatry 49, 195–205.CrossRefGoogle ScholarPubMed