Host-parasite interaction associated with major mental illness

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  • Shin-Ichi Kano, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Colin A Hodgkinson, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
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  • Lorraine Jones-Brando, Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Sharon Eastwood, Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom. morten.kringelbach@queens.ox.ac.uk.
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  • Koko Ishizuka, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Minae Niwa, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Eric Y Choi, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Daniel J Chang, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Yian Chen, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Swetha D Velivela, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Flora Leister, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Joel Wood, Departments of Psychiatry and Human Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
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  • Kodavali Chowdari, Departments of Psychiatry and Human Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
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  • Francesca Ducci, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
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  • Daniel A Caycedo, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
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  • Elizabeth Heinz, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
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  • Emily R Newman, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
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  • Nicola Cascella, Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Preben B Mortensen
  • Peter P Zandi, Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, 624 N. Broadway, Baltimore, MD, 21205, USA.
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  • Faith Dickerson, Stanley Research Program, Sheppard Pratt Health System, Baltimore, MD, 21204, USA.
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  • Vishwajit Nimgaonkar, Departments of Psychiatry and Human Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
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  • David Goldman, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
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  • Paul J Harrison, Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom. morten.kringelbach@queens.ox.ac.uk.
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  • Robert H Yolken, Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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  • Akira Sawa, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. asawa1@jhmi.edu.

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.

OriginalsprogEngelsk
TidsskriftMolecular Psychiatry
Vol/bind25
Nummer1
Sider (fra-til)194-205
Antal sider12
ISSN1359-4184
DOI
StatusUdgivet - jan. 2020

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