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Abnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients

Molecular Psychiatry volume 7, pages 673–682 (2002)Cite this article

Abstract

Epidermal growth factor (EGF) comprises a structurally related family of proteins containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFα) that regulates the development of dopaminergic neurons as well as monoamine metabolism. We assessed the contribution of EGF to schizophrenia by measuring EGF family protein levels in postmortem brains and in fresh serum of schizophrenic patients and control subjects. EGF protein levels were decreased in the prefrontal cortex and striatum of schizophrenic patients, whereas the levels of HB-EGF and TGFα were not significantly different in any of the regions examined. Conversely, EGF receptor expression was elevated in the prefrontal cortex. Serum EGF levels were markedly reduced in schizophrenic patients, even in young, drug-free patients. Chronic treatment of animals with the antipsychotic drug haloperidol had no influence on EGF levels in the brain or serum. These findings suggest that there is abnormal EGF production in various central and peripheral tissues of patients with both acute and chronic schizophrenia. EGF might thus provide a molecular substrate for the pathologic manifestation of the illness, although additional studies are required to determine a potential link between impaired EGF signaling and the pathology/etiology of schizophrenia.

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Acknowledgements

We thank Ms E Higuchi for technical assistance. This work was supported by the Japanese Society for the Promotion of Science (RFTF-96L00203), the Targeted Research Grant for Brain Science, and grants-in-aid for Creative Scientific Research and for Basic Scientific Research (B).

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Authors and Affiliations

  1. Molecular Neurobiology, Brain Research Institute, Niigata University, Japan

    T Futamura, K Toyooka & H Nawa

  2. Department of Psychiatry, Niigata University School of Medicine, Japan

    K Toyooka & T Someya

  3. Matsuzawa Hospital, Tokyo, Japan

    S Iritani, K Niizato, R Nakamura & K Tsuchiya

  4. Pathology & Brain Disease Research Center, Brain Research Institute, Niigata University, Japan

    A Kakita & H Takahashi

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Correspondence to H Nawa.

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Futamura, T., Toyooka, K., Iritani, S. et al. Abnormal expression of epidermal growth factor and its receptor in the forebrain and serum of schizophrenic patients. Mol Psychiatry 7, 673–682 (2002). https://doi.org/10.1038/sj.mp.4001081

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