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

Seva G. Khambadkone; Zachary A. Cordner; Faith Dickerson; Emily G. Severance; Emese Prandovszky; Mikhail Pletnikov; Jianchun Xiao; Ye Li; Gretha J. Boersma; C. Conover Talbot; Wayne W. Campbell; Christian S. Wright; C. Evan Siple; Timothy H. Moran; Kellie L. Tamashiro; Robert H. Yolken

doi:10.1038/s41380-018-0105-6

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

Seva G. Khambadkone, Zachary A. Cordner, Faith Dickerson, Emily G. Severance, Emese Prandovszky, Mikhail Pletnikov, Jianchun Xiao, Ye Li, Gretha J. Boersma, C. Conover Talbot, Wayne W. Campbell, Christian S. Wright, C. Evan Siple, Timothy H. Moran, Kellie L. Tamashiro, Robert H. Yolken

School of Medicine

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Pages (from-to)	560-571
Number of pages	12
Journal	Molecular psychiatry
Volume	25
Issue number	3
DOIs	https://doi.org/10.1038/s41380-018-0105-6
State	Published - Mar 1 2020

ASJC Scopus subject areas

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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Khambadkone, S. G., Cordner, Z. A., Dickerson, F., Severance, E. G., Prandovszky, E., Pletnikov, M., Xiao, J., Li, Y., Boersma, G. J., Talbot, C. C., Campbell, W. W., Wright, C. S., Siple, C. E., Moran, T. H., Tamashiro, K. L., & Yolken, R. H. (2020). Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats. Molecular psychiatry, 25(3), 560-571. https://doi.org/10.1038/s41380-018-0105-6

Khambadkone, SG, Cordner, ZA, Dickerson, F, Severance, EG , Prandovszky, E, Pletnikov, M, Xiao, J, Li, Y, Boersma, GJ, Talbot, CC, Campbell, WW, Wright, CS, Siple, CE, Moran, TH , Tamashiro, KL & Yolken, RH 2020, 'Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats', Molecular psychiatry, vol. 25, no. 3, pp. 560-571. https://doi.org/10.1038/s41380-018-0105-6

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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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AU - Prandovszky, Emese

AU - Pletnikov, Mikhail

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AU - Boersma, Gretha J.

AU - Talbot, C. Conover

AU - Campbell, Wayne W.

AU - Wright, Christian S.

AU - Siple, C. Evan

AU - Moran, Timothy H.

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AU - Yolken, Robert H.

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

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