期刊
PSYCHOPHARMACOLOGY
卷 232, 期 2, 页码 399-409出版社
SPRINGER
DOI: 10.1007/s00213-014-3669-0
关键词
(R,S)-ketamine; Antidepressant; Treatment-resistant depression; Bipolar depression; D-serine; N-methyl-D-aspartate receptor; Serine racemase; Plasma response marker
资金
- Intramural Research Program of the National Institute on Aging of the National Institutes of Health (NIH)
- Intramural Research Program of the National Institute of Mental Health of the National Institutes of Health (NIH)
- Spanish Ministry of Science and Technology (MCIT) [CTQ2011-23562]
- EADS CASA
- NATIONAL INSTITUTE ON AGING [ZIAAG000297, ZIAAG000295] Funding Source: NIH RePORTER
(R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism. The aim of the study was to examine the relationship between baseline plasma concentrations of D-serine and its precursor L-serine and antidepressant response to (R,S)-ketamine in TRD patients. Plasma samples were obtained from 21 TRD patients at baseline, 60 min before initiation of the (R,S)-ketamine infusion. Patients were classified as KET-Rs (n = 8) or KET-NRs (n = 13) based upon the difference in Montgomery-sberg Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion, with response defined as a a parts per thousand yen50 % decrease in MADRS score. The plasma concentrations of D-serine and L-serine were determined using liquid chromatography-mass spectrometry. Baseline D-serine plasma concentrations were significantly lower in KET-Rs (3.02 +/- 0.21 mu M) than in KET-NRs (4.68 +/- 0.81 mu M), p < 0.001. A significant relationship between baseline D-serine plasma concentrations and percent change in MADRS at 230 min was determined using a Pearson correlation, r = 0.77, p < 0.001, with baseline D-serine explaining 60 % of the variance in (R,S)-ketamine response. The baseline concentrations of L-serine (L-Ser) in KET-Rs were also significantly lower than those measured in KET-NRs (66.2 +/- 9.6 mu M vs 242.9 +/- 5.6 mu M, respectively; p < 0.0001). The results demonstrate that the baseline D-serine plasma concentrations were significantly lower in KET-Rs than in KET-NRs and suggest that this variable can be used to predict an antidepressant response following (R,S)-ketamine administration.
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