Host–parasite interaction associated with major mental illness

Shin ichi Kano, Colin A. Hodgkinson, Lorraine Jones-Brando, Sharon Eastwood, Koko Ishizuka, Minae Niwa, Eric Y. Choi, Daniel J. Chang, Yian Chen, Swetha D. Velivela, Flora Leister, Joel Wood, Kodavali Chowdari, Francesca Ducci, Daniel A. Caycedo, Elizabeth Heinz, Emily R. Newman, Nicola Cascella, Preben B. Mortensen, Peter P. ZandiFaith Dickerson, Vishwajit Nimgaonkar, David Goldman, Paul J. Harrison, Robert H. Yolken, Akira Sawa

Research output: Contribution to journalArticle

Abstract

Clinical studies frequently report that patients with major mental illness such as schizophrenia and bipolar disorder have co-morbid physical conditions, suggesting that systemic alterations affecting both brain and peripheral tissues might underlie the disorders. Numerous studies have reported elevated levels of anti-Toxoplasma gondii (T. gondii) antibodies in patients with major mental illnesses, but the underlying mechanism was unclear. Using multidisciplinary epidemiological, cell biological, and gene expression profiling approaches, we report here multiple lines of evidence suggesting that a major mental illness-related susceptibility factor, Disrupted in schizophrenia (DISC1), is involved in host immune responses against T. gondii infection. Specifically, our cell biology and gene expression studies have revealed that DISC1 Leu607Phe variation, which changes DISC1 interaction with activating transcription factor 4 (ATF4), modifies gene expression patterns upon T. gondii infection. Our epidemiological data have also shown that DISC1 607 Phe/Phe genotype was associated with higher T. gondii antibody levels in sera. Although further studies are required, our study provides mechanistic insight into one of the few well-replicated serological observations in major mental illness.

Original languageEnglish (US)
Pages (from-to)194-205
Number of pages12
JournalMolecular psychiatry
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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  • Cite this

    Kano, S. I., Hodgkinson, C. A., Jones-Brando, L., Eastwood, S., Ishizuka, K., Niwa, M., Choi, E. Y., Chang, D. J., Chen, Y., Velivela, S. D., Leister, F., Wood, J., Chowdari, K., Ducci, F., Caycedo, D. A., Heinz, E., Newman, E. R., Cascella, N., Mortensen, P. B., ... Sawa, A. (2020). Host–parasite interaction associated with major mental illness. Molecular psychiatry, 25(1), 194-205. https://doi.org/10.1038/s41380-018-0217-z