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Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats

Molecular Psychiatry volume 25, pages 560–571 (2020)Cite this article

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Abstract

Mania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individuals without a psychiatric disorder. We found that a history of eating nitrated dry cured meat but not other meat or fish products was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24–5.45, p < 8.97 × 10−8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in hyperactivity reminiscent of human mania, alterations in brain pathways that have been implicated in human bipolar disorder, and changes in intestinal microbiota. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions.

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Acknowledgements

This work was supported by a NIMH P50 Silvio O. Conte Center at Johns Hopkins (grant# MH-94268), the American Academy of Neurology Medical Student Research Award, the William C. Walker fund of the Johns Hopkins Department of Psychiatry and Behavioral Science, and by the Stanley Medical Research Institute.

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Author notes

  1. Gretha J. Boersma

    Present address: GGZ Drenthe Mental Health Institute, Department of Forensic Psychiatry, Assen, The Netherlands

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Seva G. Khambadkone, Zachary A. Cordner, Mikhail Pletnikov, Gretha J. Boersma, Timothy H. Moran & Kellie L. Tamashiro

  2. Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Seva G. Khambadkone, Timothy H. Moran & Kellie L. Tamashiro

  3. Sheppard Pratt Health System, Baltimore, MD, USA

    Faith Dickerson

  4. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Emily G. Severance, Emese Prandovszky, Jianchun Xiao, Ye Li & Robert H. Yolken

  5. Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C. Conover Talbot Jr.

  6. Department of Nutrition Science, Purdue University, West Lafayette, IN, USA

    Wayne W. Campbell & Christian S. Wright

  7. Mobtown Meatsnacks, Baltimore, MD, USA

    C. Evan Siple

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  1. Seva G. Khambadkone
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Khambadkone, S.G., Cordner, Z.A., Dickerson, F. et al. Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats. Mol Psychiatry 25, 560–571 (2020). https://doi.org/10.1038/s41380-018-0105-6

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