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Tytuł:
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Effects of infliximab on brain neurochemistry of adults with bipolar depression.
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Autorzy:
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Mansur RB; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Subramaniapillai M; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Lee Y; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Pan Z; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Carmona NE; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychology, Ryerson University, Toronto, ON, Canada.
Shekotikhina M; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; University of Ottawa, Department of Psychiatry, Ottawa, ON, Canada.
Iacobucci M; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Rodrigues N; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Nasri F; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Rosenblat JD; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Brietzke E; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Kingston General Hospital, Providence Care Hospital, Department of Psychiatry, Queen's University School of Medicine, Kingston, ON, Canada.
Cosgrove VE; Department of Psychiatry & Behavioral Sciences, Stanford University, School of Medicine, Palo Alto, CA, USA.
Kramer NE; Department of Psychiatry & Behavioral Sciences, Stanford University, School of Medicine, Palo Alto, CA, USA.
Suppes T; Department of Psychiatry & Behavioral Sciences, Stanford University, School of Medicine, Palo Alto, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA.
Newport J; Department of Psychiatry, Dalhousie University, Halifax, Canada.
Hajek T; Department of Psychiatry, Dalhousie University, Halifax, Canada.
McIntyre RS; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
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Źródło:
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Journal of affective disorders [J Affect Disord] 2021 Feb 15; Vol. 281, pp. 61-66. Date of Electronic Publication: 2020 Dec 03.
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Typ publikacji:
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Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
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MeSH Terms:
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Bipolar Disorder*/drug therapy
Neurochemistry*
Adult ; Aspartic Acid ; Brain/diagnostic imaging ; Glutamic Acid ; Humans ; Infliximab/therapeutic use ; Prefrontal Cortex ; Proton Magnetic Resonance Spectroscopy
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Grant Information:
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K08 CA237528 United States CA NCI NIH HHS; 142255 Canada CIHR
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Contributed Indexing:
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Keywords: bipolar disorder; cognition; inflammation; infliximab; magnetic resonance spectroscopy; neurochemistry
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Substance Nomenclature:
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30KYC7MIAI (Aspartic Acid)
3KX376GY7L (Glutamic Acid)
B72HH48FLU (Infliximab)
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Entry Date(s):
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Date Created: 20201209 Date Completed: 20210421 Latest Revision: 20210421
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Update Code:
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20240104
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DOI:
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10.1016/j.jad.2020.11.128
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PMID:
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33296798
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Objectives: To explore the relationship between inflammation and neuronal metabolism in bipolar disorder (BD) by evaluating the neurochemical effects of the tumor necrosis factor-α (TNF-α) antagonist infliximab among individuals with bipolar depression METHODS: This is a post-hoc, exploratory analysis from a 12-week, randomized, double-blind, placebo-controlled trial with infliximab for adults with bipolar depression. We assessed the effects of infliximab on concentration of metabolites in the prefrontal cortex, using proton-magnetic resonance spectroscopy ( 1 H-MRS), as well as its association with clinical outcomes (i.e. depressive symptom severity and cognitive function).
Results: Eighteen participants in the placebo and 15 in the infliximab group were included in this analysis. In the pre-specified primary outcome, there were no significant effects of treatment on prefrontal concentrations of N-acetylaspartate (NAA; p = 0.712). In the secondary analyses, there was a significant treatment by time interaction for glutamate (Glx; p = 0.018), indicating that Glx levels decreased in infliximab-treated patients, relative to placebo. Treatment group significantly moderated the association between changes in Glx levels and changes in a neurocognitive test (i.e. Digit Symbol Substitution Test; p = 0.014), indicating that in infliximab-treated participants reductions in Glx were associated with cognitive improvement.
Conclusions: Treatment with infliximab did not affect prefrontal NAA concentration in adults with BD. Exploratory analysis suggested a potential effect of treatment on the glutamate system, a finding that should be confirmed and validated by additional studies.
(Copyright © 2020. Published by Elsevier B.V.)
