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Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders

Molecular Psychiatry volume 7, pages 985–994 (2002)Cite this article

Abstract

Glucocorticoid receptors (GR) mediate the direct effects of glucocorticoids released in response to stress and the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system through a negative feedback mechanism. Individuals with major mental illness, who often exhibit hypercortisolemia, may have down-regulated levels of GR mRNA. In situ hybridization for GR mRNA was performed on post-mortem specimens from patients suffering from depression, bipolar disorder, schizophrenia and from normal controls (n = 15 per group). In frontal cortex, GR mRNA levels were decreased in layers III–VI in the subjects with depression and schizophrenia. In inferior temporal cortex, GR mRNA levels were decreased in layer IV in all three diagnostic groups. In the entorhinal cortex, GR mRNA levels were decreased in layers III and VI in the bipolar group. In hippocampus, GR mRNA levels were reduced in the dentate gyrus, CA4, CA3 and CA1 in the schizophrenia group. In the subiculum, GR mRNA levels were reduced in the bipolar group. These results suggest that GR dysregulation occurs in all three major psychiatric illnesses with variability according to anatomical site. The severity and heterogeneity of this reduction may underlie some of the clinical heterogeneity seen in these disorders.

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We thank John Bartko for statistical consultation.

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  1. Department of Psychiatry, Stanley Foundation Laboratory of Brain Research, Uniformed Services University of Health Sciences, Bethesda, MD, USA

    M J Webster, M B Knable, J O'Grady & J Orthmann

  2. Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA

    C S Weickert

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Webster, M., Knable, M., O'Grady, J. et al. Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Mol Psychiatry 7, 985–994 (2002). https://doi.org/10.1038/sj.mp.4001139

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