The role of adipokines in the rapid antidepressant effects of ketamine.
Rodrigo Machado‐Vieira, Philip W Gold, D A Luckenbaugh, E D Ballard, Erica M. Richards, Ioline D. Henter, R T De Sousa, Mark J. Niciu, P Yuan, Carlos A. Zarate
Molecular Psychiatry January 2017 DOI: 10.1038/mp.2016.36 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Adults meeting DSM-IV criteria for major depressive disorder or bipolar disorder I/II currently experiencing a major depressive episode, with treatment-resistant depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg over 40 minutes |
| Duration | Single infusion; plasma measured at baseline, 230 minutes post infusion, and day 1 post infusion |
| Measures | Montgomery-Asberg Depression Rating Scale, Hamilton Depression Rating Scale |
| Topics | Esketamine Ketamine |
| Key findings | Lower baseline adiponectin levels significantly predicted greater antidepressant response to a single ketamine infusion, which the authors suggest reflects an adverse metabolic state. Ketamine also decreased resistin, a pro-inflammatory adipokine, suggesting its anti-inflammatory effects may be partly transduced through resistin. The authors propose adipokines may predict response to ketamine or contribute to its therapeutic effects. |
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-1 for 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.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
Citations in the library
Cited by 30
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Translational Psychiatry March 21, 2017
- Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder International Journal of Environmental Research and Public Health April 17, 2018
- Targeting inflammation in depression: Ketamine as an anti-inflammatory antidepressant in psychiatric emergency Brain, Behavior, & Immunity - Health November 1, 2021
- Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile Drug Discovery Today February 1, 2023
and 25 more in the library
Cites 3
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression The Journal of Clinical Psychiatry May 15, 2014
- Brain-Derived Neurotrophic Factor and Initial Antidepressant Response to anN-Methyl-D-Aspartate Antagonist The Journal of Clinical Psychiatry September 8, 2009