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Decreased glutamate/glutamine levels may mediate cytidine's efficacy in treating bipolar depression: a longitudinal proton magnetic resonance spectroscopy study

Cited 34 time in Web of Science Cited 41 time in Scopus
Authors
Yoon, Sujung J; Lyoo, In Kyoon; Haws, Charlotte; Kim, Tae-Suk; Cohen, Bruce M; Renshaw, Perry F
Issue Date
2009-02-06
Publisher
Nature Publishing Group
Citation
Neuropsychopharmacology 34(7):1810-1818
Keywords
cytidineglutamateglutaminebipolar depressiontreatmentproton magnetic resonance spectroscopyGlutamic Acid/*metabolismGlutamine/*metabolismLongitudinal StudiesMagnetic Resonance ImagingMagnetic Resonance Spectroscopy/methodsProtons/diagnostic usePsychiatric Status Rating Scales
Abstract
Targeting the glutamatergic system has been suggested as a promising new option for developing treatment strategies for bipolar depression. Cytidine, a pyrimidine, may exert therapeutic effects through a pathway that leads to altered neuronal-glial glutamate cycling. Pyrimidines are also known to exert beneficial effects on cerebral phospholipid metabolism, catecholamine synthesis, and mitochondrial function, which have each been linked to the pathophysiology of bipolar depression. This study was aimed at determining cytidine's efficacy in bipolar depression and at assessing the longitudinal effects of cytidine on cerebral glutamate/glutamine levels. Thirty-five patients with bipolar depression were randomly assigned to receive the mood-stabilizing drug valproate plus either cytidine or placebo for 12 weeks. Midfrontal cerebral glutamate/glutamine levels were measured using proton magnetic resonance spectroscopy before and after 2, 4, and 12 weeks of oral cytidine administration. Cytidine supplementation was associated with an earlier improvement in depressive symptoms (weeks 1-4; p=0.02, 0.001, 0.002, and 0.004, respectively) and also produced a greater reduction in cerebral glutamate/glutamine levels in patients with bipolar depression (weeks 2, 4, and 12; p=0.004, 0.004, and 0.02, respectively). Cytidine-related glutamate/glutamine decrements correlated with a reduction in depressive symptoms (p=0.001). In contrast, these relationships were not observed in the placebo add-on group. The study results suggest that cytidine supplementation of valproate is associated with an earlier treatment response in bipolar depression. Furthermore, cytidine's efficacy in bipolar depression may be mediated by decreased levels of cerebral glutamate and/or glutamine, consistent with alterations in excitatory neurotransmission.
ISSN
1470-634X (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19194376

http://hdl.handle.net/10371/67433
DOI
https://doi.org/10.1038/npp.2009.2
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College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
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