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Behavioral activation therapy for depression is associated with a reduction in the concentration of circulating quinolinic acid

Published online by Cambridge University Press:  25 November 2020

Jonathan Savitz Open the ORCID record for Jonathan Savitz [Opens in a new window] ,
Bart N. Ford ,
Hung-Wen Yeh ,
Elisabeth Akeman ,
Kelly Cosgrove ,
Ashley N. Clausen ,
Christopher Martell ,
Namik Kirlic ,
Jessica Santiago  and
T. Kent Teague
...Show all authors
Jonathan Savitz*
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA
Bart N. Ford
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA
Hung-Wen Yeh
Affiliation:
Childrens’ Mercy Hospital, Kansas City, MO, USA
Elisabeth Akeman
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA
Kelly Cosgrove
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA Department of Psychology, The University of Tulsa, Tulsa, OK, USA
Ashley N. Clausen
Affiliation:
Kansas City VA Healthcare System, Kansas City, MO, USA Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, MO, USA
Christopher Martell
Affiliation:
Department of Psychological and Brain Sciences, University of Massachusetts Amherst, Amherst, MO, USA
Namik Kirlic
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA
Jessica Santiago
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA
T. Kent Teague
Affiliation:
Department of Surgery, University of Oklahoma School of Community Medicine, Tulsa, OK, USA Department of Psychiatry, University of Oklahoma School of Community Medicine, Tulsa, OK, USA Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, OK, USA
Michael R. Irwin
Affiliation:
Cousins Center for Psychoneuroimmunology at UCLA, Semel Institute for Neuroscience and UCLA David Geffen School of Medicine, Los Angeles, CA, USA
Martin P. Paulus
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA
Robin L. Aupperle*
Affiliation:
Laureate Institute for Brain Research, Tulsa, OK, USA Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA
*
Author for correspondence: Jonathan Savitz, E-mail: jsavitz@laureateinstitute.org, Robin Aupperle, E-mail: raupperle@laureateinstitute.org
Author for correspondence: Jonathan Savitz, E-mail: jsavitz@laureateinstitute.org, Robin Aupperle, E-mail: raupperle@laureateinstitute.org
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Abstract

Background

An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.

Methods

Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).

Results

BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). Neither the change in KynA/QA, nor baseline KynA/QA were associated with response to BA therapy.

Conclusion

The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.

Keywords

Kynurenine pathwaymajor depressive disorderquinolinic acid
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 13 , October 2022 , pp. 2500 - 2509
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press.

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Footnotes

‡

The online version of this article has been updated since original publication. A notice detailing the changes has also been published at https://doi.org/10.1017/S0033291721002683

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