Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-22T17:39:41.809Z Has data issue: false hasContentIssue false
  • English
  • Français

Dorsolateral prefrontal N-acetyl-aspartate concentration in male patients with chronic schizophrenia and with chronic bipolar disorder

Published online by Cambridge University Press:  16 April 2020

V. Molina ,
J. Sánchez ,
J. Sanz ,
S. Reig ,
C. Benito ,
I. Leal ,
F. Sarramea ,
R. Rebolledo ,
T. Palomo  and
M. Desco
V. Molina*
Affiliation:
Department of Psychiatry, Hospital Clínico Universitario, Paseo de San Vicente 58-182, E-37007Salamanca, Spain
J. Sánchez
Affiliation:
Department of Experimental Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
J. Sanz
Affiliation:
Department of Psychiatry, Hospital Doce de Octubre, Madrid, Spain
S. Reig
Affiliation:
Department of Experimental Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
C. Benito
Affiliation:
Department of Radiology, Hospital Gregorio Marañón, Madrid, Spain
I. Leal
Affiliation:
Department of Psychiatry, Hospital de Jaén, Jaén, Spain
F. Sarramea
Affiliation:
Department of Psychiatry, Hospital de Jaén, Jaén, Spain
R. Rebolledo
Affiliation:
Department of Psychiatry, Hospital Doce de Octubre, Madrid, Spain
T. Palomo
Affiliation:
Department of Psychiatry, Hospital Doce de Octubre, Madrid, Spain
M. Desco
Affiliation:
Department of Experimental Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
*
*Corresponding author. Tel./fax: +34923291448. E-mail address: [email protected] (V. Molina).
Get access

Abstract

Objectives

A study of N-acetyl-aspartate (NAA) can provide data of interest about cortical alterations in psychotic illnesses. Although a decreased NAA level in the cerebral cortex is a replicated finding in chronic schizophrenia, the data are less consistent for bipolar disease. On the other hand, it is likely that NAA values in schizophrenia may differ in men and women.

Methods

We used proton magnetic resonance spectroscopy (1H MRS) to examine NAA levels in the prefrontal cortex in two groups of male patients, one with schizophrenia (n = 11) and the other with bipolar disorder (n = 13) of similar duration, and compared them to a sample of healthy control males (n = 10). Additionally, we compared the degree of structural deviations from normal volumes of gray matter (GM) and cerebrospinal fluid (CSF) in the dorsolateral prefrontal cortex.

Results

Compared to controls, schizophrenia and bipolar patients presented decreased NAA to creatine ratios, while only the schizophrenia group showed an increase in CSF in the dorsolateral prefrontal region. There were no differences in choline to creatine ratios among the groups.

Conclusions

These data suggest that the decrease in NAA in the prefrontal region may be similar in schizophrenia and bipolar disorder, at least in the chronic state. However, cortical CSF may be markedly increased in schizophrenia patients.

Keywords

SchizophreniaBipolar disorderN-acetyl-aspartateSpectroscopyPrefrontal cortex
Type
Original article
Information
European Psychiatry , Volume 22 , Issue 8 , November 2007 , pp. 505 - 512
Copyright
Copyright © Elsevier Masson SAS 2007

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

Amaral, J.A., Tamada, R.S., Issler, C.K., Caetano, S.C., Cerri, G.G., de Castro, C.C.et al.A (1) HMRS study of the anterior cingulate gyrus in euthymic bipolar patients. Hum Psychopharmacol 2006;21:215–220.CrossRefGoogle ScholarPubMed
Andreasen, N.C., Rajarethinam, R., Cizadlo, T., Arndt, S., Swayze, V.W.2nd Flashman, L.A.et al.Automatic atlas-based volume estimation of human brain regions from MR images. J Comput Assist Tomogr 1996;20:98–106.CrossRefGoogle ScholarPubMed
Angelie, E., Bonmartin, A., Boudraa, A., Gonnaud, P.M., Mallet, J.J., Sappey-Marinier, D.Regional differences and metabolic changes in normal aging of the human brain: proton MR spectroscopic imaging study. Am J Neuroradiol 2001;22:119–127.Google ScholarPubMed
Ashburner, J., Friston, K.J.Multimodal image coregistration and partitioning - a unified framework. Neuroimage 1997;6:209–217.CrossRefGoogle ScholarPubMed
Ashburner, J., Friston, K.J.Voxel-based morphometry—the methods. Neuroimage 2000;11:805–821.CrossRefGoogle Scholar
Bertolino, A., Callicott, J.H., Elman, I., Mattay, V.S., Tedeschi, G., Frank, J.A.et al.Regionally specific neuronal pathology in untreated patients with schizophrenia: a proton magnetic resonance spectroscopic imaging study. Biol Psychiatry 1998;43:641–648.CrossRefGoogle ScholarPubMed
Bertolino, A., Callicott, J.H., Mattay, V.S., Weidenhammer, K.M., Rakow, R., Egan, M.F.et al.The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia. Biol Psychiatry 2001;49:39–46.CrossRefGoogle ScholarPubMed
Bertolino, A., Frye, M., Callicott, J.H., Mattay, V.S., Rakow, R., Shelton-Repella, J.et al.Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging. Biol Psychiatry 2003;53:906–913.CrossRefGoogle ScholarPubMed
Bottomley, P.A.Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci 1987;508:333–348.CrossRefGoogle ScholarPubMed
Brambilla, P., Stanley, J.A., Sassi, R.B., Nicoletti, M.A., Mallinger, A.G., Keshavan, M.S.et al.1H MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration. Neuropsychopharmacology 2004;29:1918–1924.CrossRefGoogle ScholarPubMed
Brooks, J.C., Roberts, N., Kemp, G.J., Gosney, M.A., Lye, M., Whitehouse, G.H.A proton magnetic resonance spectroscopy study of age-related changes in frontal lobe metabolite concentrations. Cereb Cortex 2001;11:598–605.CrossRefGoogle ScholarPubMed
Buckley, P.F., Moore, C., Long, H., Larkin, C., Thompson, P., Mulvany, F.et al.1H-magnetic resonance spectroscopy of the left temporal and frontal lobes in schizophrenia: clinical, neurodevelopmental, and cognitive correlates. Biol Psychiatry 1994;36:792–800.CrossRefGoogle ScholarPubMed
Bustillo, J.R., Lauriello, J., Rowland, L.M., Jung, R.E., Petropoulos, H., Hart, B.L.et al.Effects of chronic haloperidol and clozapine treatments on frontal and caudate neurochemistry in schizophrenia. Psychiatry Res 2001;107:135–149.CrossRefGoogle Scholar
Cecil, K.M., DelBello, M.P., Morey, R., Strakowski, S.M.Frontal lobe differences in bipolar disorder as determined by proton MR spectroscopy. Bipolar Disord 2002;4:357–365.CrossRefGoogle ScholarPubMed
Cecil, K.M., DelBello, M.P., Sellars, M.C., Strakowski, S.M.Proton magnetic resonance spectroscopy of the frontal lobe and cerebellar vermis in children with a mood disorder and a familial risk for bipolar disorders. J Child Adolesc Psychopharmacol 2003;13:545–555.CrossRefGoogle Scholar
Craddock, N., O'Donovan, M.C., Owen, M.J.The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J Med Genet 2005;42:193–204.CrossRefGoogle ScholarPubMed
Dager, S.R., Friedman, S.D., Parow, A., Demopulos, C., Stoll, A.L., Lyoo, I.K.et al.Brain metabolic alterations in medication-free patients with bipolar disorder. Arch Gen Psychiatry 2004;61:450–458.CrossRefGoogle ScholarPubMed
Deicken, R.F., Eliaz, Y., Feiwell, R., Schuff, N.Increased thalamic N-acetylaspartate in male patients with familial bipolar I disorder. Psychiatry Res 2001;106:35–45.CrossRefGoogle ScholarPubMed
Deicken, R.F., Zhou, L., Corwin, F., Vinogradov, S., Weiner, M.W.Decreased left frontal lobe N-acetylaspartate in schizophrenia. Am J Psychiatry 1997;154:688–690.Google Scholar
Desco, M., Pascau, J., Reig, S., Gispert, J.D., Santos, A., Benito, B.et al.Multimodality Image Quantification Using Talairach Grid. Proc SPIE Medical Imaging 2001;4422:1385–1392.CrossRefGoogle Scholar
Hedges, L.V., Olkin, I.Statistical methods for meta-analysis. San Diego, CA: Academic Press; 1985.Google Scholar
Hollingshead, A., Frederick, R.Social stratification and psychiatric disorders. Am Soc Rev 1953;18:163–189.CrossRefGoogle Scholar
Kates, W.R., Warsofsky, I.S., Patwardhan, A., Abrams, M.T., Liu, A.M., Naidu, S.et al.Automated Talairach atlas-based parcellation and measurement of cerebral lobes in children. Psychiatry Res 1999;91:11–30.CrossRefGoogle ScholarPubMed
Keshavan, M.S., Stanley, J.A., Pettegrew, J.W.Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings—part II. Biol Psychiatry 2000;48:369–380.CrossRefGoogle ScholarPubMed
Kreis, R., Ernst, T., Ross, B.D.Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magn Reson Med 1993;30:424–437.CrossRefGoogle ScholarPubMed
Lim, K.O., Adalsteinsson, E., Spielman, D., Sullivan, E.V., Rosenbloom, M.J., Pfefferbaum, A.Proton magnetic resonance spectroscopic imaging of cortical gray and white matter in schizophrenia. Arch Gen Psychiatry 1998;55:346–352.CrossRefGoogle Scholar
Lim, K.O., Rosenbloom, M.J., Faustman, W.O., Sullivan, E.V., Pfefferbaum, A.Cortical gray matter deficit in patients with bipolar disorder. Schizophr Res 1999;40:219–227.CrossRefGoogle ScholarPubMed
McDonald, C., Bullmore, E.T., Sham, P.C., Chitnis, X., Wickham, H., Bramon, E.et al.Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch Gen Psychiatry 2004;61:974–984.CrossRefGoogle ScholarPubMed
McIntosh, A.M., Job, D.E., Moorhead, T.W., Harrison, L.K., Forrester, K., Lawrie, S.M.et al.Voxel-based morphometry of patients with schizophrenia or bipolar disorder and their unaffected relatives. Biol Psychiatry 2004;56:544–552.CrossRefGoogle ScholarPubMed
Molina, V., Sánchez, J., Reig, S., Sanz, J., Benito, C., Santamarta, C.et al.N-acetyl-aspartate in the dorsolateral prefrontal region in the early years of schizophrenia are inversely related to illness duration. Schizophrenia Res 2005;73:209–219.CrossRefGoogle Scholar
Molina, V., Reig, S., Sanz, J., Palomo, T., Benito, C., Sánchez, J.et al.Increase in gray matter volume and decrease in white matter volume in the cerebral cortex during treatment with atypical neuroleptics in schizophrenia. Schizophrenia Res 2005;80:61–71.CrossRefGoogle Scholar
Molina, V., Reig, S., Sarramea, F., Sanz, J.F., Artaloytia, J., Luque, R.et al.Anatomical and functional brain variables associated to clozapine response in treatment-resistant schizophrenia. Psychiatry Res Neuroimaging 2003;124:153–161.CrossRefGoogle ScholarPubMed
Molina, V., Sanz, J., Sarramea, F., Benito, C., Palomo, T.Lower prefrontal gray matter volume in schizophrenia in chronic but not in first episode schizophrenia patients. Psychiatry Res 2004;131:45–56.CrossRefGoogle ScholarPubMed
Moore, C.M., Breeze, J.L., Gruber, S.A., Babb, S.M., Frederick, B.B., Villafuerte, R.A.et al.Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex. Bipolar Disord 2000;2:207–216.CrossRefGoogle ScholarPubMed
Moore, G.J., Bebchuk, J.M., Hasanat, K., Chen, G., Seraji-Bozorgzad, N., Wilds, I.B.et al.Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects?. Biol Psychiatry 2000;48:1–8.CrossRefGoogle ScholarPubMed
Nopoulos, P., Flaum, M., Andreasen, N.C.Sex differences in brain morphology in schizophrenia. Am J Psychiatry 1997;154:1648–1654.CrossRefGoogle Scholar
Nudmamud, S., Reynolds, L.M., Reynolds, G.P.N-acetylaspartate and N-Acetylaspartylglutamate deficits in superior temporal cortex in schizophrenia and bipolar disorder: a postmortem study. Biol Psychiatry 2003;53:1138–1141.CrossRefGoogle ScholarPubMed
Pfefferbaum, A., Lim, K.O., Zipursky, R.B., Mathalon, D.H., Rosenbloom, M.J., Lane, B.et al.Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. Alcohol Clin Exp Res 1992;16:1078–1089.CrossRefGoogle ScholarPubMed
Rajkowska, G., Miguel-Hidalgo, J.J., Makkos, Z., Meltzer, H., Overholser, J., Stockmeier, C.Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia. Schizophr Res 2002;57:127–138.CrossRefGoogle Scholar
Schlaepfer, T.E., Harris, G.J., Tien, A.Y., Peng, L.W., Lee, S., Federman, E.B.et al.Decreased regional cortical gray matter volume in schizophrenia. Am J Psychiatry 1994;151:842–848.Google Scholar
Sharma, R., Venkatasubramanian, P.N., Bárány, M., Davis, J.M.Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients. Schizophr Res 1992;8:43–49.CrossRefGoogle ScholarPubMed
Stark, A.K., Uylings, H.B., Sanz-Arigita, E., Pakkenberg, B.Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am J Psychiatry 2004;161:882–888.CrossRefGoogle ScholarPubMed
Talairach, J., Tournoux, P.Co-planar stereotaxic atlas of the human brain. Stuttgart: Thieme Medical; 1988.Google Scholar
Urenjak, J., Williams, S.R., Gadian, D.G., Noble, M.Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 1993;13:981–989.CrossRefGoogle ScholarPubMed
van den Boogaart, A., van Ormondt, D., Pijnapel, W.W.F., de Beer, R., Ala-Korpela, M.Removal of the water resonance from 1H magnetic resonance spectra In: McWhirter, J.G. editor. Mathematics in Processing III. Oxford: 1994. p. 175–195.Google Scholar
Vanhamme, L., van den Boogaart, A., Van Huffel, S.Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 1997;129:35–43.CrossRefGoogle ScholarPubMed
Winsberg, M.E., Sachs, N., Tate, D.L., Adalsteinsson, E., Spielman, D., Ketter, T.A.Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiatry 2000;47:475–481.CrossRefGoogle ScholarPubMed
Woods, B.T.Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry 1998;155:1661–1670.CrossRefGoogle Scholar
Zipursky, R.B., Seeman, M.V., Bury, A., Langevin, R., Wortzman, G., Katz, R.Deficits in gray matter volume are present in schizophrenia but not bipolar disorder. Schizophr Res 1997;26:85–92.CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.