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Host–parasite interaction associated with major mental illness

Molecular Psychiatry volume 25, pages 194–205 (2020)Cite this article

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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.

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Acknowledgements

We thank Dr. Wayne Yu and microarray facility at Sidney Kimmel Comprehensive Cancer Center (Johns Hopkins University) for microarray experiments; Drs.  Jian-Chun (J-C) Xiao, Teppei Tanaka, Minori Koga for technical advice; Indigo VL Rose, Pamela Talalay, Nao Gamo, and Noah Elkins for critically reading the manuscript. This work was supported by U.S. Public Health Service Grants MH-069853 (AS), Silvio O. Conte Center grant MH-094268 (AS), MH-105660 (AS), MH-107730 (AS), K99/R00MH-093458 (SK), MH-113645 (SK); by foundation grants from Stanley Medical Research Institute (AS, FD), S-R (AS), RUSK (AS), NARSAD (AS, SK), JSPS (SK); by the Hammerschlag family (SK).

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  1. Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Shin-ichi Kano, Koko Ishizuka, Minae Niwa, Eric Y. Choi, Daniel J. Chang, Yian Chen, Swetha D. Velivela, Flora Leister & Nicola Cascella

  2. Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA

    Colin A. Hodgkinson, Francesca Ducci, Daniel A. Caycedo, Elizabeth Heinz, Emily R. Newman & David Goldman

  3. Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Lorraine Jones-Brando & Robert H. Yolken

  4. Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom

    Sharon Eastwood & Paul J. Harrison

  5. Departments of Psychiatry and Human Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Joel Wood, Kodavali Chowdari & Vishwajit Nimgaonkar

  6. National Centre for Register-Based Research, University of Aarhus, Aarhus, 8000, Denmark

    Preben B. Mortensen

  7. Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21205, USA

    Peter P. Zandi & Akira Sawa

  8. Stanley Research Program, Sheppard Pratt Health System, Baltimore, MD, 21204, USA

    Faith Dickerson

  9. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Akira Sawa

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  1. Shin-ichi Kano
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Kano, Si., Hodgkinson, C.A., Jones-Brando, L. et al. Host–parasite interaction associated with major mental illness. Mol Psychiatry 25, 194–205 (2020). https://doi.org/10.1038/s41380-018-0217-z

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