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

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Title: Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals
Author(s): Keegan, MR
Chittiprol, S
Letendre, SL
Winston, A
Fuchs, D
Boasso, A
Iudicello, J
Ellis, RJ
Item Type: Journal Article
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.
Publication Date: 26-Oct-2016
Date of Acceptance: 13-Jul-2016
URI: http://hdl.handle.net/10044/1/52565
DOI: https://dx.doi.org/10.4137/IJTR.S36464
ISSN: 1178-6469
Publisher: Libertas Academica
Start Page: 79
End Page: 88
Journal / Book Title: International Journal of Tryptophan Research
Volume: 9
Copyright Statement: Creative Commons Attribution Non-Commercial License 3.0
Keywords: Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
HIV
cognitive impairment
depression
tryptophan
kynurenine
IDO
HUMAN-IMMUNODEFICIENCY-VIRUS
CENTRAL-NERVOUS-SYSTEM
EFFECTIVE ANTIRETROVIRAL THERAPY
CEREBROSPINAL-FLUID CONCENTRATIONS
AIDS DEMENTIA COMPLEX
QUALITY-OF-LIFE
QUINOLINIC ACID
IMMUNE ACTIVATION
NEUROCOGNITIVE IMPAIRMENT
TYPE-1 INFECTION
HIV
IDO
cognitive impairment
depression
kynurenine
tryptophan
Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
HIV
cognitive impairment
depression
tryptophan
kynurenine
IDO
HUMAN-IMMUNODEFICIENCY-VIRUS
CENTRAL-NERVOUS-SYSTEM
EFFECTIVE ANTIRETROVIRAL THERAPY
CEREBROSPINAL-FLUID CONCENTRATIONS
AIDS DEMENTIA COMPLEX
QUALITY-OF-LIFE
QUINOLINIC ACID
IMMUNE ACTIVATION
NEUROCOGNITIVE IMPAIRMENT
TYPE-1 INFECTION
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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