title: Shank3 as a potential biomarker of antidepressant response to ketamine and its neural correlates in bipolar depression.
abstract: BACKGROUND
  Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine.
  
  
  METHODS
  Twenty-nine subjects with bipolar depression received a double-blind, randomized, subanesthetic dose (.5 mg/kg) ketamine infusion. Of the patients for whom Shank3 levels were collected, 15 completed baseline 3-Tesla MRI and 17 completed post-ketamine [(18)F]-FDG PET.
  
  
  RESULTS
  Higher baseline Shank3 levels predicted antidepressant response at Days 1 (r=-.39, p=.047), 2 (r=-.45, p=.02), and 3 (r=-.42, p=.03) and were associated with larger average (r=.58, p=.02) and right amygdala volume (r=.65, p=.009). Greater baseline Shank3 also predicted increased glucose metabolism in the hippocampus (r=.51, p=.04) and amygdala (r=.58, p=.02).
  
  
  CONCLUSIONS
  Limitations include the small sample size, inability to assess the source of peripheral Shank3, and the lack of a placebo group for baseline Shank3 levels and comparative structural/functional neuroimaging.
  
  
  CONCLUSIONS
  Shank3 is a potential biomarker of antidepressant response to ketamine that correlates with baseline amygdala volume and increased glucose metabolism in the amygdala and hippocampus.
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Ortiz
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA; School of Nursing, University of Nevada at Las Vegas, Las Vegas, NV, USA.
authors.forename: Nada
authors.initials: N
authors.lastname: Lukkahati
authors.affiliation: National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Leorey N
authors.initials: LN
authors.lastname: Saligan
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics & Pathophysiology Branch, Building 10/Clinical Research Center (CRC), 10 Center Dr., Room 7-5342, Bethesda, MD 20892, USA. Electronic address: zaratec@mail.nih.gov.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000328:Adult; D000368:Aged; D000679:Amygdala / Q000378:metabolism; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D016202:N-Methylaspartate / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007649:Ketamine
keywords: Bipolar depression; Ketamine; MRI; PET; Shank3