TY - JOUR
T1 - Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression
AU - Park, Minkyung
AU - Newman, Laura E.
AU - Gold, Philip W.
AU - Luckenbaugh, David A.
AU - Yuan, Peixiong
AU - Machado-Vieira, Rodrigo
AU - Zarate, Carlos A.
N1 - Funding Information:
Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; NCT00088699, protocol 04-M-0222), by a NARSAD Independent Investigator Award to CAZ, and by a Brain and Behavior Mood Disorders Research Award to CAZ. A patent for the use of ketamine in depression has been awarded that lists CAZ among the inventors; he has assigned his rights on the patent to the U.S. government, but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise.
Funding Information:
Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health , National Institutes of Health (IRP-NIMH-NIH; NCT00088699 , protocol 04-M-0222), by a NARSAD Independent Investigator Award to CAZ, and by a Brain and Behavior Mood Disorders Research Award to CAZ. The NIMH, NARSAD, and the Brain & Behavior Research Foundation had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Publisher Copyright:
© 2016
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted positive antidepressant response to ketamine; 2) whether ketamine responders experienced acute changes in cytokine levels not observed in non-responders; and 3) whether ketamine lowered levels of pro-inflammatory cytokines, analogous to the impact of other antidepressants. Data from double-blind, placebo-controlled studies of patients with major depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion of sub-anesthetic dose ketamine were used (N = 80). Plasma levels of the eight cytokines were measured at baseline and at 230 min, 1 day, and 3 days post-ketamine. A significant positive correlation was observed between sTNFR1 and severity of depression at baseline. Cytokine changes did not correlate with changes in mood nor predict mood changes associated with ketamine administration. Ketamine significantly increased IL-6 levels and significantly decreased sTNFR1 levels. IL-6 and TNF-α levels were also significantly higher—and sTNFR1 levels were significantly lower—in BD compared to MDD subjects. The functional significance of this difference is unknown. Changes in cytokine levels post-ketamine were not related to antidepressant response, suggesting they are not a primary mechanism involved in ketamine's acute antidepressant effects. Taken together, the results suggest that further study of cytokine levels is warranted to assess their potential role as a surrogate outcome in the rapid antidepressant response paradigm.
AB - Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted positive antidepressant response to ketamine; 2) whether ketamine responders experienced acute changes in cytokine levels not observed in non-responders; and 3) whether ketamine lowered levels of pro-inflammatory cytokines, analogous to the impact of other antidepressants. Data from double-blind, placebo-controlled studies of patients with major depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion of sub-anesthetic dose ketamine were used (N = 80). Plasma levels of the eight cytokines were measured at baseline and at 230 min, 1 day, and 3 days post-ketamine. A significant positive correlation was observed between sTNFR1 and severity of depression at baseline. Cytokine changes did not correlate with changes in mood nor predict mood changes associated with ketamine administration. Ketamine significantly increased IL-6 levels and significantly decreased sTNFR1 levels. IL-6 and TNF-α levels were also significantly higher—and sTNFR1 levels were significantly lower—in BD compared to MDD subjects. The functional significance of this difference is unknown. Changes in cytokine levels post-ketamine were not related to antidepressant response, suggesting they are not a primary mechanism involved in ketamine's acute antidepressant effects. Taken together, the results suggest that further study of cytokine levels is warranted to assess their potential role as a surrogate outcome in the rapid antidepressant response paradigm.
KW - Bipolar disorder
KW - Cytokine
KW - Interleukin-6 (IL-6)
KW - Ketamine
KW - Major depressive disorder
KW - Soluble tumor necrosis factor receptor 1 (sTNFR1)
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U2 - 10.1016/j.jpsychires.2016.09.025
DO - 10.1016/j.jpsychires.2016.09.025
M3 - Article
C2 - 27718369
AN - SCOPUS:84991594159
SN - 0022-3956
VL - 84
SP - 113
EP - 118
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -