Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome
Drew D. Kiraly, Sarah R. Horn, Nicholas T. van Dam, Sara Costi, Jaclyn Schwartz, Seunghee Kim‐Schulze, Manishkumar Patel, Georgia E. Hodes, Scott J. Russo, Miriam Mérad, Dan V. Iosifescu, Dennis S. Charney, James W. Murrough
Translational Psychiatry March 21, 2017 DOI: 10.1038/tp.2017.31 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 59 |
| Population | Healthy controls and actively depressed patients with treatment-resistant depression (TRD), matched for age, sex, and body mass index |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Blood draws at baseline, 4 hours, and 24 hours following intravenous infusion |
| Topics | Depression Ketamine Esketamine |
| Keywords | Immune system Chemokine Depression economics Proinflammatory cytokine Antidepressant Immunology Inflammation Anesthesia Amygdala Hippocampus |
| Citations | 182 |
| Key findings | Patients with TRD show elevated interleukin-6 and a unique pattern of increased inflammatory mediators, chemokines, and colony-stimulating factors compared to healthy controls. |
Abstract
Abstract A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index. All subjects provided baseline blood samples, and TRD subjects had additional blood draw at 4 and 24 h following intravenous infusion of ketamine (0.5 mg kg −1 ). Samples underwent multiplex analysis of 41 cytokines, chemokines and growth factors using quantitative immunoassay technology. Our a priori hypothesis was that TRD patients would show elevations in canonical pro-inflammatory cytokines; analyses demonstrated significant elevation of the pro-inflammatory cytokine interleukin-6. Further exploratory analyses revealed significant regulation of four additional soluble factors in patients with TRD. Several cytokines showed transient changes in level after ketamine, but none correlated with treatment response. Low pretreatment levels of fibroblast growth factor 2 were associated with ketamine treatment response. In sum, we found that patients with TRD demonstrate a unique pattern of increased inflammatory mediators, chemokines and colony-stimulating factors, providing support for the immune hypothesis of TRD. These patterns suggest novel treatment targets for the subset of patients with TRD who evidence dysregulated immune functioning.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |
| Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression Patients with unipolar and bipolar treatment-resistant depression | 2018 | Observational cohort | n = 84 |
Citations in the library
Cited by 48
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Possible role of the gut microbiota–brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model Translational Psychiatry December 15, 2017
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- An update on ketamine and its two enantiomers as rapid-acting antidepressants Expert Review of Neurotherapeutics December 4, 2018
- Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review Journal of Psychopharmacology June 26, 2021
and 43 more in the library
Cites 8
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression The Journal of Clinical Psychiatry May 15, 2014
- Effect of Baseline Anxious Depression on Initial and Sustained Antidepressant Response to Ketamine The Journal of Clinical Psychiatry September 25, 2014
and 3 more in the library