Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression

Minkyung Park, Laura E. Newman, Philip W. Gold, David A. Luckenbaugh, Peixiong Yuan, Rodrigo Machado-Vieira, Carlos A. Zarate

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)113-118
Number of pages6
JournalJournal of Psychiatric Research
Volume84
DOIs
StatePublished - Jan 1 2017

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Treatment-Resistant Depressive Disorder
Ketamine
Antidepressive Agents
Cytokines
Major Depressive Disorder
Bipolar Disorder
Interleukin-6
Depression
Anesthetics
Placebos

Keywords

  • Bipolar disorder
  • Cytokine
  • Interleukin-6 (IL-6)
  • Ketamine
  • Major depressive disorder
  • Soluble tumor necrosis factor receptor 1 (sTNFR1)

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression. / Park, Minkyung; Newman, Laura E.; Gold, Philip W.; Luckenbaugh, David A.; Yuan, Peixiong; Machado-Vieira, Rodrigo; Zarate, Carlos A.

In: Journal of Psychiatric Research, Vol. 84, 01.01.2017, p. 113-118.

Research output: Contribution to journalArticle

Park, Minkyung ; Newman, Laura E. ; Gold, Philip W. ; Luckenbaugh, David A. ; Yuan, Peixiong ; Machado-Vieira, Rodrigo ; Zarate, Carlos A. / Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression. In: Journal of Psychiatric Research. 2017 ; Vol. 84. pp. 113-118.
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