Abstract
Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia. In 56 patients with schizophrenia and 58 healthy controls, our results confirm that levels of KYNA in saliva increase following psychological stress. The magnitude of the effect correlated negatively with proton magnetic resonance spectroscopy (MRS) glutamate + glutamine (r = −.31, p = .017) and glutamate (r = −0.27, p = .047) levels in the ACC in patients but not in the controls (all p ≥ .45). Although, a causal relationship cannot be ascertained in this cross-sectional study, these findings suggest a potentially meaningful link between central glutamate levels and kynurenine pathway response to stress in individuals with schizophrenia.
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Acknowledgements
We sincerely thank Frank Gaston and Hongji Chen for spectral processing. The support was received from the National Institutes of Health (grant numbers K23MH112010, P50 MH103222, U01MH108148, R01MH112180, R01MH094520, R01MH096263, and T32MH067533).
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Dr. Hong has received or plans to receive research funding or consulting fees from Mitsubishi, Your Energy Systems LLC, Neuralstem, Taisho Pharmaceutical, Sound Pharma, Heptares, Pfizer, and Takeda. All other authors declare no competing interests.
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Chiappelli, J., Rowland, L.M., Notarangelo, F.M. et al. Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia. Neuropsychopharmacol 43, 1706–1711 (2018). https://doi.org/10.1038/s41386-018-0072-2
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DOI: https://doi.org/10.1038/s41386-018-0072-2
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