title: The role of adipokines in the rapid antidepressant effects of ketamine.
abstract: We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg-1for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine's antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine's anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Gold
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Ballard
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Richards
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: I D
authors.initials: ID
authors.lastname: Henter
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: De Sousa
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D054392:Adipokines / Q000097:blood / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000188:drug therapy; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D005544:Forecasting; D006801:Humans; D007649:Ketamine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D052243:Resistin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; D052242:Adiponectin; D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D052243:Resistin; D007649:Ketamine