title: D-serine plasma concentration is a potential biomarker of (R,S)-ketamine antidepressant response in subjects with treatment-resistant depression.
abstract: BACKGROUND
  (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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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-Åsberg Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion, with response defined as a ≥50 % decrease in MADRS score. The plasma concentrations of D-serine and L-serine were determined using liquid chromatography-mass spectrometry.
  
  
  RESULTS
  Baseline D-serine plasma concentrations were significantly lower in KET-Rs (3.02 ± 0.21 μM) than in KET-NRs (4.68 ± 0.81 μM), 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 μM vs 242.9 ± 5.6 μM, respectively; p < 0.0001).
  
  
  CONCLUSIONS
  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.
authors: Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD, USA.
authors: Ruin
authors: R
authors: Moaddel
authors: David A
authors: DA
authors: Luckenbaugh
authors: Ying
authors: Y
authors: Xie
authors: Alma
authors: A
authors: Villaseñor
authors: Nancy E
authors: NE
authors: Brutsche
authors: Rodrigo
authors: R
authors: Machado-Vieira
authors: Anuradha
authors: A
authors: Ramamoorthy
authors: Maria Paz
authors: MP
authors: Lorenzo
authors: Antonia
authors: A
authors: Garcia
authors: Michel
authors: M
authors: Bernier
authors: Marc C
authors: MC
authors: Torjman
authors: Coral
authors: C
authors: Barbas
authors: Carlos A
authors: CA
authors: Zarate
authors: Irving W
authors: IW
authors: Wainer
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D061218:Depressive Disorder, Treatment-Resistant / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012694:Serine / Q000097:blood*; D053719:Tandem Mass Spectrometry
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D012694:Serine; D007649:Ketamine