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The possible role of the kynurenine pathway in anhedonia in adolescents

  • Biological Child and Adolescent Psychiatry - Original Article
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Abstract

To address the heterogeneous nature of adolescent major depression (MDD), we investigated anhedonia, a core symptom of MDD. We recently reported activation of the kynurenine pathway (KP), a central neuroimmunological pathway which metabolizes tryptophan (TRP) into kynurenine (KYN) en route to several neurotoxins, in a group of highly anhedonic MDD adolescents. In this study, we aimed to extend our prior work and examine the relationship between KP activity and anhedonia, measured quantitatively, in a group of MDD adolescents and in a combined group of MDD and healthy control adolescents. Thirty-six adolescents with MDD (22 medication-free) and 20 controls were included in the analysis. Anhedonia scores were generated based on clinician- and subject-rated assessments and a semi-structured clinician interview. Blood KP metabolites, collected in the AM after an overnight fast, were measured using high-performance liquid chromatography. The rate-limiting enzyme of the KP, indoleamine 2,3-dioxygenase (IDO), was estimated by the ratio of KYN/TRP. Pearson correlation tests were used to assess correlations between anhedonia scores and KP measures while controlling for MDD severity. IDO activity and anhedonia scores were positively correlated in the group psychotropic medication-free adolescents with MDD (r = 0.42, P = 0.05) and in a combined group of MDD subjects and healthy controls (including medicated patients: r = 0.30, P = 0.02; excluding medicated patients: r = 0.44, P = 0.004). In conclusions, our findings provide further support for the role for the KP, particularly IDO, in anhedonia in adolescent MDD. These results emphasize the importance of dimensional approaches in the investigation of psychiatric disorders.

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Acknowledgments

This study was supported by grants from NIH (AT002395, MH077072, AT004576), the American Foundation for Suicide Prevention, the NYU School of Medicine General Clinical Research Center grant (M01-RR00096), the Leon Levy Foundation, and generous gifts from the Anita Saltz Foundation and from Bruce and Claude Wasserstein.

Statement regarding human subjects: All procedures described in this manuscript have been approved by the NYU Institutional Review Board and New York City Health and Hospital Corporation; procedures comply with the ethical standards established in the 1964 Declaration of Helsinki. All subjects involved in the study provided informed consent prior to inclusion.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, NYU Child Study Center, NYU School of Medicine, New York University Langone Medical Center, 577 First Avenue, New York, NY, 10016, USA

    Vilma Gabbay & Benjamin A. Ely

  2. Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd #35, Orangeburg, NY, 10962, USA

    Vilma Gabbay

  3. Radiology, Research, NYU School of Medicine, Bellevue C&D Building 122, 462 First Avenue, New York, NY, 10016, USA

    James Babb

  4. Cancer Institute, Tisch Hospital, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA

    Leonard Liebes

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  1. Vilma Gabbay
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Correspondence to Vilma Gabbay.

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Gabbay, V., Ely, B.A., Babb, J. et al. The possible role of the kynurenine pathway in anhedonia in adolescents. J Neural Transm 119, 253–260 (2012). https://doi.org/10.1007/s00702-011-0685-7

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  • DOI: https://doi.org/10.1007/s00702-011-0685-7

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