Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression

S H Fatemi, J. A. Earle, T. McMenomy

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333 Scopus citations

Abstract

Accumulation of neurobiological knowledge points to neurodevelopmental origins for certain psychotic and mood disorders. Recent landmark postmortem reports implicate Reelin, a secretory glycoprotein responsible for normal lamination of brain, in the pathology of schizophrenia and bipolar disorders. We employed quantitative immunocytochemistry to measure levels of Reelin protein in various compartments of hippocampal formation in subjects diagnosed with schizophrenia, bipolar disorder and major depression compared to normal controls. Significant reductions were observed in Reelin-positive adjusted cell densities in the dentate molecular layer (ANOVA, P < 0.001), CA4 area (ANOVA, P < 0.001), total hippocampal area (ANOVA, P < 0.038) and in Reelin-positive cell counts in CA4 (ANOVA, P < 0.042) of schizophrenics vs controls. Adjusted Reelin-positive cell densities were also reduced in CA4 areas of subjects with bipolar disorder (ANOVA, P < 0.001) and nonsignificantly in those with major depression. CA4 areas were also significantly reduced in schizophrenic (ANOVA, P < 0.009) patients. No significant effects of confounding variables were found. The exception was that family history of psychiatric illness correlated strongly with Reelin reductions in several areas of hippocampus (CA4, adjusted cell density, F=13.77, P=0.001). We present new immunocytochemical evidence showing reductions in Reelin expression in hippocampus of subjects with schizophrenia, bipolar disorder and major depression and confirm recent reports documenting a similar deficit involving Reelin expression in brains of subjects with schizophrenia and bipolar disorder.

Original languageEnglish (US)
Pages (from-to)654-663
Number of pages10
JournalMolecular psychiatry
Volume5
Issue number6
DOIs
StatePublished - 2000

Bibliographical note

Funding Information:
Supported by Minnesota Medical Foundation and Stanley Foundation grants (SHF). We are grateful to Dr Andre M Goffinet for his generous gifts of G10 and 142 antibodies and to the Stanley Foundation Neuropathology Consortium Brain Bank for provision of brain samples courtesy of Drs LB Bigelow, J Cervenak, MM Herman, TN Hyde, JE Kleinman, M Knable, JD Paltan, RM Post, EF Torrey, MJ Webster and RH Yolken. We are indebted to Dr Joel Hektner for his astute statistical help with reanalysis of data. We appreciate the helpful comments provided by Drs E Costa, A Guidotti, C Pesold, SC Schulz and M Knable regarding this manuscript. We appreciate the secretarial assistance of Ms Janet Holland and Ms Heather Winstead, and careful review of data by Mr Joel Stary.

Keywords

  • Bipolar disorder
  • Hippocampus
  • Immunocytochemistry
  • Major depression
  • Reelin
  • Schizophrenia

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