Effects of infliximab on brain neurochemistry of adults with bipolar depression

Rodrigo B. Mansur; Mehala Subramaniapillai; Yena Lee; Zihang Pan; Nicole E. Carmona; Margarita Shekotikhina; Michelle Iacobucci; Nelson Rodrigues; Flora Nasri; Joshua D. Rosenblat; Elisa Brietzke; Victoria E. Cosgrove; Nicole E. Kramer; Trisha Suppes; Jason Newport; Tomas Hajek; Roger S. McIntyre

doi:10.1016/j.jad.2020.11.128

Effects of infliximab on brain neurochemistry of adults with bipolar depression

Rodrigo B. Mansur, Mehala Subramaniapillai, Yena Lee, Zihang Pan, Nicole E. Carmona, Margarita Shekotikhina, Michelle Iacobucci, Nelson Rodrigues, Flora Nasri, Joshua D. Rosenblat, Elisa Brietzke, Victoria E. Cosgrove, Nicole E. Kramer, Trisha Suppes, Jason Newport, Tomas Hajek, Roger S. McIntyre

Medicine

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

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 (¹H-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.

Original language	English
Pages (from-to)	61-66
Number of pages	6
Journal	Journal of Affective Disorders
Volume	281
DOIs	https://doi.org/10.1016/j.jad.2020.11.128
Publication status	Published - Feb 15 2021

Bibliographical note

Funding Information:
This study was supported by grant 13T-012 from the Stanley Medical Research Institute, and by grant 142255 from the Canadian Institutes of Health Research. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Publisher Copyright:
© 2020

ASJC Scopus Subject Areas

Clinical Psychology
Psychiatry and Mental health

PubMed: MeSH publication types

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jad.2020.11.128

Cite this

Mansur, R. B., Subramaniapillai, M., Lee, Y., Pan, Z., Carmona, N. E., Shekotikhina, M., Iacobucci, M., Rodrigues, N., Nasri, F., Rosenblat, J. D., Brietzke, E., Cosgrove, V. E., Kramer, N. E., Suppes, T., Newport, J., Hajek, T., & McIntyre, R. S. (2021). Effects of infliximab on brain neurochemistry of adults with bipolar depression. Journal of Affective Disorders, 281, 61-66. https://doi.org/10.1016/j.jad.2020.11.128

Mansur, RB, Subramaniapillai, M, Lee, Y, Pan, Z, Carmona, NE, Shekotikhina, M, Iacobucci, M, Rodrigues, N, Nasri, F, Rosenblat, JD, Brietzke, E, Cosgrove, VE, Kramer, NE, Suppes, T, Newport, J, Hajek, T & McIntyre, RS 2021, 'Effects of infliximab on brain neurochemistry of adults with bipolar depression', Journal of Affective Disorders, vol. 281, pp. 61-66. https://doi.org/10.1016/j.jad.2020.11.128

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title = "Effects of infliximab on brain neurochemistry of adults with bipolar depression",

abstract = "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 (1H-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.",

author = "Mansur, {Rodrigo B.} and Mehala Subramaniapillai and Yena Lee and Zihang Pan and Carmona, {Nicole E.} and Margarita Shekotikhina and Michelle Iacobucci and Nelson Rodrigues and Flora Nasri and Rosenblat, {Joshua D.} and Elisa Brietzke and Cosgrove, {Victoria E.} and Kramer, {Nicole E.} and Trisha Suppes and Jason Newport and Tomas Hajek and McIntyre, {Roger S.}",

note = "Funding Information: This study was supported by grant 13T-012 from the Stanley Medical Research Institute, and by grant 142255 from the Canadian Institutes of Health Research. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2020",

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doi = "10.1016/j.jad.2020.11.128",

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T1 - Effects of infliximab on brain neurochemistry of adults with bipolar depression

AU - Mansur, Rodrigo B.

AU - Subramaniapillai, Mehala

AU - Lee, Yena

AU - Pan, Zihang

AU - Carmona, Nicole E.

AU - Shekotikhina, Margarita

AU - Iacobucci, Michelle

AU - Rodrigues, Nelson

AU - Nasri, Flora

AU - Rosenblat, Joshua D.

AU - Brietzke, Elisa

AU - Cosgrove, Victoria E.

AU - Kramer, Nicole E.

AU - Suppes, Trisha

AU - Newport, Jason

AU - Hajek, Tomas

AU - McIntyre, Roger S.

N1 - Funding Information: This study was supported by grant 13T-012 from the Stanley Medical Research Institute, and by grant 142255 from the Canadian Institutes of Health Research. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2020

PY - 2021/2/15

Y1 - 2021/2/15

N2 - 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 (1H-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.

AB - 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 (1H-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.

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Effects of infliximab on brain neurochemistry of adults with bipolar depression

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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