Original articles| Volume 56, ISSUE 11, P844-852, December 01, 2004

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Reduced glucocorticoid and estrogen receptor alpha messenger ribonucleic acid levels in the amygdala of patients with major mental illness

  • William R. Perlman
    Address reprint requests to William R. Perlman, Ph.D., National Institute of Mental Health, Clinical Brain Disorders Branch, 10 Center Drive, Room 4N313C, Bethesda, MD 20892-1385.
    Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services
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  • Maree J. Webster
    Stanley Foundation Laboratory of Brain Research, Department of Psychiatry, Uniformed Services University of Health Sciences, Bethesda, Maryland.
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  • Joel E. Kleinman
    Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services
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  • Cynthia Shannon Weickert
    Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services
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      The amygdala is a limbic structure involved in the stress response and the regulation of emotional behaviors, both of which are disrupted in patients with neuropsychiatric illnesses. Because glucocorticoids are mediators of the stress response, we hypothesized that glucocorticoid receptor (GR) messenger ribonucleic acid (mRNA) levels might be altered in the amygdala. We also hypothesized that estrogen receptor α (ERα) mRNA expression might be altered in the amygdala, on the basis of observed gender differences in mental illness.


      Using quantitative film autoradiography after in situ hybridization with human GR and ERα probes, we measured mRNA levels on adjacent amygdala sections in four groups (n = 15 each of subjects with schizophrenia, major depressive disorder, and bipolar disorder, and unaffected control subjects) provided by the Stanley Consortium.


      We detected main effects of diagnosis and exposure to antidepressant medication on the levels of both mRNAs but no main effect of gender. Compared with control subjects, GR mRNA expression was reduced in the basolateral/lateral nuclei in schizophrenia and bipolar disorder. Estrogen receptor α mRNA levels were reduced in the basomedial nucleus in major depressive disorder and bipolar disorder.


      Our results support and extend previous findings describing a pattern of steroid hormone mRNA alterations that differs depending on which brain region is being examined in a given mental illness.

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