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Decreased serum L-arginine and L-citrulline levels in major depression

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Abstract

Rationale

It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated.

Objectives

The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD.

Methods

Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs).

Results

L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 μmol/L and 84.89 + 25.16, p = 0.04 μmol/L and L-citrulline 31.58 + 6.05 μmol/L and 35.19 + 6.85 μmol/L, p = 0.03, respectively).

Conclusions

The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

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Acknowledgments

We acknowledge the major contribution of Janisse Khudabux-Der who was the research nurse and coordinator of the study.

Funding

This work was supported by the Canadian Institute of Health Research (CIHR) (grant MOP-69026) and the University of Alberta Hospital Foundation to J-M Le Melledo (principal applicant), G. Gyenes, S. Newman, R. Tsuyuki, G. Baker and S. Archer.)

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Authors and Affiliations

  1. Department of Psychiatry, University of Alberta, 114th street, Edmonton, AB, T6G 2B7, Canada

    S. Hess, S. Newman & Jean-Michel Le Melledo

  2. Department of Psychiatry, Neurochemical Research Unit, University of Alberta, 114th street, Edmonton, AB, T6G 2B7, Canada

    G. Baker

  3. Department of Cardiology, University of Alberta, 114th street, Edmonton, AB, T6G 2B7, Canada

    G. Gyenes & R. Tsuyuki

  4. University of Alberta Hospital, 114th street, Edmonton, AB, T6G 2B7, Canada

    Jean-Michel Le Melledo

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  1. S. Hess
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  2. G. Baker
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  3. G. Gyenes
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  4. R. Tsuyuki
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  6. Jean-Michel Le Melledo
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Correspondence to Jean-Michel Le Melledo.

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Hess, S., Baker, G., Gyenes, G. et al. Decreased serum L-arginine and L-citrulline levels in major depression. Psychopharmacology 234, 3241–3247 (2017). https://doi.org/10.1007/s00213-017-4712-8

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  • DOI: https://doi.org/10.1007/s00213-017-4712-8

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