Skip to main content
SpringerLink
Log in

Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

The ratio of albumin in cerebrospinal fluid (CSF) to serum may serve as an index of the integrity of the blood-CSF barrier, with increases in this ratio indicating increased permeability. The ratio of immunoglobulin G (IgG) in CSF to serum (divided by the albumin ratio to correct for variance in blood-CSF permeability) represents an index of the endogenous production of IgG in the central nervous system (CNS), with increases reflecting a possible infectious and/or autoimmune process stimulating central IgG synthesis. We analyzed simultaneously collected CSF and serum samples from 46 schizophrenic subjects, 8 of whom were studied both on and off neuroleptic treatment, and samples from 20 normal controls. The data indicated increases in CSF/ serum albumin ratios or CSF/serum IgG indices in 22% and 20%, respectively, of the schizophrenic patients. Only 3 patients showed elevations in both indices. Comparison of values on and off neuroleptics indicated no significant effect of neuroleptics on these indices.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahokas A, Koskiniemi M, Vaheri A, Rimon R (1985) Altered white cell count, protein concentration and oligoclonal IgG bands in the cerebrospinal fluid of many patients with acute psychiatric disorders. Neuropsychobiology 14: 1–4

    Google Scholar 

  • American Psychiatric Association, Committee on Nomenclature and Statistics (1980) Diagnostic and statistical manual of mental disorders, 3rd ed. Washington, D.C.

  • Axelsson R, Martensson E, Alling C (1982) Impairment of the blood-brain barrier as an aetiological factor in paranoid psychosis. Br J Psychiatry 141: 273–281

    Google Scholar 

  • Bauer K, Kornhuber J (1987) Blood-cerebrospinal fluid in schizophrenic patients. Eur Arch Psychiatr Neurol Sci 236: 257–259

    Google Scholar 

  • Bock E (1978) Immunoglobulins, prealbumin, transferrin, albumin, and alpha2-macroglobulin in cerebrospinal fluid and serum in schizophrenic patients. Birth Defects 14: 283–295

    Google Scholar 

  • Bock E, Rafaelson OJ (1974) Schizophrenia: proteins in blood and cerebrospinal fluid. Dan Med Bull 21: 93–105

    Google Scholar 

  • Braun U, Braun G, Sargent T (1980) Changes in the blood-brain barrier permeability resulting from d-amphetamine, 6-hydroxydopamine and pimozide measured by a new technique. Experientia 36: 207–209

    Google Scholar 

  • Bruetsch VL, Bahr MA, Skobba JS, Dieter VJ (1942) The group of dementia praecox patients with an increase of the protein content of the cerebrospinal fluid. J Nerv Ment Dis 95: 669–679

    Google Scholar 

  • Burns EM, Nasrallah HA, Kathol M, Kruckeberg TW, Coffman JA (1987) Right vs. left hemispheric blood-brain barrier permeability in schizophrenia: a dynamic computed tomographic study. Psychiatry Res 22: 229–241

    Google Scholar 

  • Caroscio JT, Kochwa S, Sacks H, Cohen JA, Yahr MD (1983) Quantitative CSF IgG measurements in multiple sclerosis and other neurological diseases. Arch Neurol 40: 409–413

    Google Scholar 

  • Christenson RH, Russel ME, Bell YL (1988) Immunoassays for immunoglobulin G (IgG) in cerebrospinal fluid (CSF) compared. Clin Chem 34: 1158

    Google Scholar 

  • Cutler RWP (1980) Neurochemical aspects of blood-brain-cerebrospinal fluid barriers. In: Wood JH (ed) Neurobiology of cerebrospinal fluid. Plenum, New York, pp 41–51

    Google Scholar 

  • DeLisi LE, Crow TJ (1986) Is schizophrenia a viral or immunologic disorder? Psychiatr Clin North Am 9: 115–132

    Google Scholar 

  • Dysken M, Patlak CS, Dobben GD, Pettigrew KD, Bartko JJ, Burns EM, Davis J, Regier DA (1987) Rapid dynamic CT scanning to distinguish schizophrenic from normal subjects. Psychiatry Res 20: 165–175

    Google Scholar 

  • Felgenhauer K (1974) Protein size and cerebrospinal fluid composition. Klin Wochenschr 52: 1158–1164

    Google Scholar 

  • Ganrot K, Laurell CB (1974) Measurement of IgG and albumin content of cerebrospinal fluid, and its interpretation. Clin Chem 20: 571–573

    Google Scholar 

  • Goldstein GW, Betz AL (1986) The blood-brain barrier. Sci Am 255: 74–83

    Google Scholar 

  • Harrington MG, Merril CR, Torrey EF (1985) Differences in cerebrospinal fluid proteins between patients with schizophrenia and normal persons. Clin Chem 31: 722–726

    Google Scholar 

  • Killingsworth LM (1982) Clinical applications of protein determinations in biological fluids other than blood. Clin Chem 28: 1093–1102

    Google Scholar 

  • Kirch DG, Kaufmann CA, Papadopolous NM, Martin B, Weinberger DR (1985) Abnormal cerebrospinal fluid protein indices in schizophrenia. Biol Psychiatry 20: 1039–1046

    Google Scholar 

  • Knight JG (1982) Dopamine-receptor-stimulating autoantibodies: a possible cause of schizophrenia. Lancet: 1073–1076

  • Lampson LA (1987) Molecular bases of the immune response to neural antigens. TINS 10: 211–216

    Google Scholar 

  • Link H, Tibbling G (1977) Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis. Scand J Clin Lab Invest 37: 397–401

    Google Scholar 

  • Papadopoulos NM, Costello R, Kay AD, Cutler NR, Rapaport SI (1984) Combined immunochemical and electrophoretic determinations of proteins in paired serum and cerebrospinal fluid samples. Clin Chem 30: 1814–1816

    Google Scholar 

  • Papadopoulos NM, McFarlin DE, Patranas NJ, McFarland HF, Costello R (1987) A comparison between chemical analysis and magnetic resonance imaging with the clinical diagnosis of multiple sclerosis. Am J Clin Pathol 88: 365–368

    Google Scholar 

  • Pearson EK (1973) Study of cerebrospinal fluid in schizophrenics: a review of the literature. Psychopharmacol Bull 9: 59–62

    Google Scholar 

  • Pert CB, Knight JC, Laing P, Markwell MAK (1988) Scenarios for a viral etiology of schizophrenia. Schizophr Bull 14: 243–247

    Google Scholar 

  • Preskorn SH, Irwin GH, Simpson S, Friesen D, Rinne J, Jerkovich G (1981) Medical therapies for mood disorders alter the blood-brain barrier. Science 213: 469–471

    Google Scholar 

  • Reese TS, Karnovsky MJ (1967) Five structural localizations of a blood-brain barrier to exogeneous peroxidase. J Cell Biol 34: 207–217

    Google Scholar 

  • Roos RP, Davis K, Meltzer HY (1985) Immunoglobulin studies in patients with psychiatric diseases. Arch Gen Psychiatry 42: 124–128

    Google Scholar 

  • Schliep G, Felgenhauer K (1978) Serum-CSF protein gradients, the blood-CSF barrier and local immune response. J Neurol 218: 77–96

    Google Scholar 

  • Shapiro WR (1988) Cerebrospinal fluid circulation and the blood-brain barrier. Ann NY Acad Sci 531: 9–14

    Google Scholar 

  • Shelton RC, Karson CN, Doran AR, Pickar D, Bigelow LB, Weinberger DR (1988) Cerebral structural pathology in schizophrenia: evidence for a selective prefrontal cortical deficit. Am J Psychiatry 145: 154–163

    Google Scholar 

  • Stevens JR (1988) Schizophrenia and multiple sclerosis. Schizophr Bull 14: 231–241

    Google Scholar 

  • Stevens JR, Papadopoulos NM, Resnick M (1990) Oligoclonal bands in acute schizophrenia: a negative search. Acta Psychiatr Scand 81: 262–264

    Google Scholar 

  • Synek W, Reuben JR (1976) The ventricular brain ratio using planimetric measurement of EMI scans. Br J Radiol 49: 233–237

    Google Scholar 

  • Tibbling G, Link H, Ohman S (1977) Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 37: 385–390

    Google Scholar 

  • Torrey EF, Kaufmann CA (1986) Schizophrenia and neuroviruses. In: Nasrallah HA, Weinberger DR (eds) The neurology of schizophrenia. Elsevier, Amsterdam, pp 361–376

    Google Scholar 

  • Torrey EF, Albrecht P, Behr DE (1985) Permeability of the blood-brain barrier in psychiatric patients. Am J Psychiatry 142: 657–658

    Google Scholar 

  • Tourtellotte WW, Potvin AR, Fleming JO, Murphy KN, Levy K, Syndulko K, Potvin JH (1980) Multiple sclerosis: measurement and validation of central nervous system IgG synthesis rate. Neurology 30: 240–244

    Google Scholar 

  • van Kammen DP, Sternberg DE (1980) Cerebrospinal fluid studies in schizophrenia. In: Wood JH (ed) Neurobiology of cerebrospinal fluid. Plenum, New York, pp 719–742

    Google Scholar 

  • Winfield JB, Shaw M, Silverman LM, Eisenberg RA, Wilson HA, Koffler D (1983) Intrathecal IgG synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction. Am J Med 74: 837–844

    Google Scholar 

Download references

Author information

Author notes

  1. D. G. Kirch

    Present address: Division of Clinical Research, National Institute of Mental Health, Rockville, Washington, D. C., Maryland

Authors and Affiliations

  1. Neuropsychiatry Branch, National Institute of Mental Health, Rockville, Washington, D. C., Maryland

    D. G. Kirch, R. C. Alexander, R. L. Suddath, C. A. Kaufmann & R. J. Wyatt

  2. Clinical and Research Services Branch, National Institute of Mental Health, Rockville, Washington, D. C., Maryland

    D. G. Daniel

  3. Chemistry Service, National Institutes of Health, Bethesda, Maryland, USA

    N. M. Papadopoulos

Authors
  1. D. G. Kirch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. C. Alexander
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. L. Suddath
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. M. Papadopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. A. Kaufmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. G. Daniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. J. Wyatt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirch, D.G., Alexander, R.C., Suddath, R.L. et al. Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia. J. Neural Transmission 89, 219–232 (1992). https://doi.org/10.1007/BF01250674

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01250674

Keywords

Search

Navigation