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Int J Tryptophan Res. 2016 Oct 26;9:79-88. eCollection 2016.

Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals.

Author information

1
Imperial College London, Department of Medicine, London, United Kingdom.; ViiV Healthcare Ltd., Clinical Sciences Group, London, United Kingdom.
2
University of California, San Diego, Departments of Neurosciences and Psychiatry, San Diego, CA, USA.; Memorial Healthcare System, Department of Pathology, Hollywood, FL, USA.
3
University of California, San Diego, Departments of Neurosciences and Psychiatry, San Diego, CA, USA.
4
Imperial College London, Department of Medicine, London, United Kingdom.
5
Innsbruck Medical University, Centre for Chemistry and Biomedicine, Innsbruck, Austria.
6
Imperial College London, Centre for Immunology and Vaccinology, London, United Kingdom.

Abstract

OBJECTIVE:

Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals.

METHODS:

In a cross-sectional analysis, concentrations of neopterin (NEO), tumor necrosis factor-alpha, TRP, KYN, KYN/TRP ratio, phenylalanine (PHE), tyrosine (TYR), PHE/TYR ratio, and nitrite were assessed in the cerebrospinal fluid (CSF) and plasma of HIV+ (n = 91) and HIV-negative (HIV-) individuals (n = 66). CI and MDD were assessed via a comprehensive neuropsychological test battery. A Global Deficit Score ≥0.5 was defined as CI. Nonparametric statistical analyses included Kruskal-Wallis and Mann-Whitney U tests, and multivariate logistic regression.

RESULTS:

Following Bonferroni correction, NEO concentrations were found to be greater in CSF and TRP concentration was found to be lower in the plasma of HIV+ versus HIV- individuals, including a subgroup of aviremic (defined as HIV-1 RNA <50 cps/mL) HIV+ participants receiving antiretroviral therapy (n = 44). There was a nonsignificant trend toward higher KYN/TRP ratios in plasma in the HIV+ group (P = 0.027; Bonferroni corrected α = 0.0027). In a logistic regression model, lower KYN/TRP ratios in plasma were associated with CI and MDD in the overall HIV+ group (P = 0.038 and P = 0.063, respectively) and the aviremic subgroup (P = 0.066 and P = 0.027, respectively), though this observation was not statistically significant following Bonferroni correction (Bonferroni corrected α = 0.0031).

CONCLUSIONS:

We observed a trend toward lower KYN/TRP ratios in aviremic HIV+ patients with CI and MDD.

KEYWORDS:

HIV; IDO; cognitive impairment; depression; kynurenine; tryptophan

Conflict of interest statement

MRK is employed by, and owns shares in, ViiV Healthcare Ltd. AW discloses honoraria, research grants, or consultancy fees from, or a role as an investigator in clinical trials sponsored by, Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Roche, Pfizer and ViiV Healthcare, all outside the work presented here. SLL discloses lecture honorarium, unpaid consultancy and a research grant paid to his institution from Gilead Sciences; consultancy and a research grant paid to his institution from ViiV Healthcare; consultancy for Merck & Co. Inc.; and lecture honorarium from Janssen, all unrelated to the work presented here. Other authors disclose no potential conflicts of interest.

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