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Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium

Molecular Psychiatry volume 9, pages 609–620 (2004)Cite this article

Abstract

Between 1997 and 2002, 48 data sets from the hippocampus were produced on samples from the Stanley Neuropathology Consortium. From these data sets, 224 total measures were available from the various subdivisions of the hippocampus. An integrative analysis of these measures was performed using a multivariate, nonparametric analysis of variance (ANOVA). ANOVA with correction for multiple comparisons indicated that parvalbumin-containing cells in CA2 were reduced in schizophrenia and bipolar disorder. In addition, reelin protein in the molecular layer of the dentate gyrus was decreased in schizophrenia, bipolar disorder, and depression at the trend level of statistical significance (P=0.065). These results strongly suggest a dysfunction of inhibitory GABA-ergic interneurons in severe mental illness. Without correction for multiple comparisons, 31 measures were abnormal in at least one disease, whereas 11 measures would be expected to appear abnormal by chance. Abnormal molecules included measures of synaptic density or neuronal plasticity (reelin, SNAP-25, BDNF, Complexin I and II), as well as parvalbumin, tyrosine receptor kinase A, glucocorticoid receptors, glutamate NR1 receptor subunits, serotonin 5HT2A and 5HT1B receptors, and dopamine D5 receptors.

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Authors and Affiliations

  1. The Stanley Medical Research Institute, Bethesda, MD, USA

    M B Knable, B M Barci & E F Torrey

  2. Stanley Brain Research Laboratory, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, USA

    M J Webster & E F Torrey

  3. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

    J Meador-Woodruff

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  1. M B Knable
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Correspondence to M B Knable.

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Knable, M., Barci, B., Webster, M. et al. Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium. Mol Psychiatry 9, 609–620 (2004). https://doi.org/10.1038/sj.mp.4001471

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