Reversal of the kynurenine pathway of tryptophan catabolism may improve depression in ART-treated HIV-infected ugandans

Priscilla Martinez, Alexander C. Tsai, Conrad Muzoora, Annet Kembabazi, Sheri D. Weiser, Yong Huang, Jessica E. Haberer, Jeffrey N. Martin, David Bangsberg, Peter W. Hunt

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Major depressive disorder is highly prevalent among HIV-infected persons, and depression symptom severity improves during the course of HIV antiretroviral therapy (ART). The potential biologic pathways explaining these phenomena remain unclear. We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3- dioxygenase-1 and potentially other sources) may correlate with improvements in depression symptom severity in this setting. Method: We used the first year of data from the Uganda AIDS Rural Treatment Outcomes Study, a prospective cohort of 504 HIVinfected individuals initiating their first ART regimen in rural Uganda. We fitted random-effects regression models to estimate the associations between plasma tryptophan, plasma kynurenine, dietary diversity, and self-reported depression symptom severity. Results: Greater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan (KT) ratio over 12-month follow-up. In multivariable-adjusted models, declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity. The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets. Conclusions: Indoleamine 2,3-dioxygenase-1- mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals, particularly among those with poor dietary protein intake. ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms. Interventions to reduce immune activation, and dietary protein supplementation, may be promising strategies to further reduce depression in this setting.

Original languageEnglish (US)
Pages (from-to)456-462
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume65
Issue number4
DOIs
StatePublished - Apr 1 2014
Externally publishedYes

Fingerprint

Kynurenine
Tryptophan
HIV
Depression
Indoleamine-Pyrrole 2,3,-Dioxygenase
Uganda
Therapeutics
Dietary Proteins
Diet
Major Depressive Disorder
Dietary Supplements
Acquired Immunodeficiency Syndrome
Proteins
Outcome Assessment (Health Care)

Keywords

  • Antiretroviral therapy
  • Depression
  • Indoleamine 2,3-dioxygenase-1
  • Sub-Saharan Africa
  • Tryptophan catabolism

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Reversal of the kynurenine pathway of tryptophan catabolism may improve depression in ART-treated HIV-infected ugandans. / Martinez, Priscilla; Tsai, Alexander C.; Muzoora, Conrad; Kembabazi, Annet; Weiser, Sheri D.; Huang, Yong; Haberer, Jessica E.; Martin, Jeffrey N.; Bangsberg, David; Hunt, Peter W.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 65, No. 4, 01.04.2014, p. 456-462.

Research output: Contribution to journalArticle

Martinez, Priscilla ; Tsai, Alexander C. ; Muzoora, Conrad ; Kembabazi, Annet ; Weiser, Sheri D. ; Huang, Yong ; Haberer, Jessica E. ; Martin, Jeffrey N. ; Bangsberg, David ; Hunt, Peter W. / Reversal of the kynurenine pathway of tryptophan catabolism may improve depression in ART-treated HIV-infected ugandans. In: Journal of Acquired Immune Deficiency Syndromes. 2014 ; Vol. 65, No. 4. pp. 456-462.
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abstract = "Background: Major depressive disorder is highly prevalent among HIV-infected persons, and depression symptom severity improves during the course of HIV antiretroviral therapy (ART). The potential biologic pathways explaining these phenomena remain unclear. We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3- dioxygenase-1 and potentially other sources) may correlate with improvements in depression symptom severity in this setting. Method: We used the first year of data from the Uganda AIDS Rural Treatment Outcomes Study, a prospective cohort of 504 HIVinfected individuals initiating their first ART regimen in rural Uganda. We fitted random-effects regression models to estimate the associations between plasma tryptophan, plasma kynurenine, dietary diversity, and self-reported depression symptom severity. Results: Greater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan (KT) ratio over 12-month follow-up. In multivariable-adjusted models, declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity. The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets. Conclusions: Indoleamine 2,3-dioxygenase-1- mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals, particularly among those with poor dietary protein intake. ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms. Interventions to reduce immune activation, and dietary protein supplementation, may be promising strategies to further reduce depression in this setting.",
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T1 - Reversal of the kynurenine pathway of tryptophan catabolism may improve depression in ART-treated HIV-infected ugandans

AU - Martinez, Priscilla

AU - Tsai, Alexander C.

AU - Muzoora, Conrad

AU - Kembabazi, Annet

AU - Weiser, Sheri D.

AU - Huang, Yong

AU - Haberer, Jessica E.

AU - Martin, Jeffrey N.

AU - Bangsberg, David

AU - Hunt, Peter W.

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Background: Major depressive disorder is highly prevalent among HIV-infected persons, and depression symptom severity improves during the course of HIV antiretroviral therapy (ART). The potential biologic pathways explaining these phenomena remain unclear. We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3- dioxygenase-1 and potentially other sources) may correlate with improvements in depression symptom severity in this setting. Method: We used the first year of data from the Uganda AIDS Rural Treatment Outcomes Study, a prospective cohort of 504 HIVinfected individuals initiating their first ART regimen in rural Uganda. We fitted random-effects regression models to estimate the associations between plasma tryptophan, plasma kynurenine, dietary diversity, and self-reported depression symptom severity. Results: Greater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan (KT) ratio over 12-month follow-up. In multivariable-adjusted models, declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity. The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets. Conclusions: Indoleamine 2,3-dioxygenase-1- mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals, particularly among those with poor dietary protein intake. ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms. Interventions to reduce immune activation, and dietary protein supplementation, may be promising strategies to further reduce depression in this setting.

AB - Background: Major depressive disorder is highly prevalent among HIV-infected persons, and depression symptom severity improves during the course of HIV antiretroviral therapy (ART). The potential biologic pathways explaining these phenomena remain unclear. We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3- dioxygenase-1 and potentially other sources) may correlate with improvements in depression symptom severity in this setting. Method: We used the first year of data from the Uganda AIDS Rural Treatment Outcomes Study, a prospective cohort of 504 HIVinfected individuals initiating their first ART regimen in rural Uganda. We fitted random-effects regression models to estimate the associations between plasma tryptophan, plasma kynurenine, dietary diversity, and self-reported depression symptom severity. Results: Greater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan (KT) ratio over 12-month follow-up. In multivariable-adjusted models, declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity. The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets. Conclusions: Indoleamine 2,3-dioxygenase-1- mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals, particularly among those with poor dietary protein intake. ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms. Interventions to reduce immune activation, and dietary protein supplementation, may be promising strategies to further reduce depression in this setting.

KW - Antiretroviral therapy

KW - Depression

KW - Indoleamine 2,3-dioxygenase-1

KW - Sub-Saharan Africa

KW - Tryptophan catabolism

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