TY - JOUR
T1 - Kynurenine pathway metabolites selectively associate with impaired associative memory function in depression
AU - Chirico, Margherita
AU - Custer, James
AU - Shoyombo, Ifeoluwa
AU - Cooper Cortes, Crystal
AU - Meldrum, Sheila
AU - Dantzer, Robert
AU - Trivedi, Madhukar H.
AU - Rathouz, Paul
AU - Toups, Marisa S.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/10
Y1 - 2020/10
N2 - Activation of the kynurenine pathway (KP), an important downstream effect of inflammation, is a driver of depression and neurodegeneration. Damage from the end product of KP activation, quinolinic acid, may be responsible specifically for impairment in hippocampally mediated memory function, among its effects. We hypothesized that associative memory – the ability to recall relationships between items – would be sensitive to KP activation because it is heavily dependent on the hippocampus. We tested a sample of N = 80 adults with unmedicated depression using a face-name task which assesses the ability to recognize, as well as to recall correct pairings, of faces and names. Plasma samples were analyzed for KP metabolites – tryptophan (TRP), kynurenine (KYN), quinolinic acid (QUIN) and kynurenic acid (KYNA). Using linear models we examined whether the KYN/TRP and QUIN/KYNA ratios predicted performance of recognition memory and associative memory, accounting for item type and the number of learning exposures to items (1 vs. 3). We found that for rearranged items viewed three times, associative memory performance was inversely related to the QUIN/KYNA ratio (p = 0.01, p = 0.001 adjusted for age, gender and race/ethnicity). Recognition memory was not associated with KP activation. The results support our hypothesis that KP activation most sensitively impacts hippocampally mediated memory function.
AB - Activation of the kynurenine pathway (KP), an important downstream effect of inflammation, is a driver of depression and neurodegeneration. Damage from the end product of KP activation, quinolinic acid, may be responsible specifically for impairment in hippocampally mediated memory function, among its effects. We hypothesized that associative memory – the ability to recall relationships between items – would be sensitive to KP activation because it is heavily dependent on the hippocampus. We tested a sample of N = 80 adults with unmedicated depression using a face-name task which assesses the ability to recognize, as well as to recall correct pairings, of faces and names. Plasma samples were analyzed for KP metabolites – tryptophan (TRP), kynurenine (KYN), quinolinic acid (QUIN) and kynurenic acid (KYNA). Using linear models we examined whether the KYN/TRP and QUIN/KYNA ratios predicted performance of recognition memory and associative memory, accounting for item type and the number of learning exposures to items (1 vs. 3). We found that for rearranged items viewed three times, associative memory performance was inversely related to the QUIN/KYNA ratio (p = 0.01, p = 0.001 adjusted for age, gender and race/ethnicity). Recognition memory was not associated with KP activation. The results support our hypothesis that KP activation most sensitively impacts hippocampally mediated memory function.
KW - Cognition
KW - Depression
KW - Kynurenine
KW - Memory
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U2 - 10.1016/j.bbih.2020.100126
DO - 10.1016/j.bbih.2020.100126
M3 - Article
C2 - 34589879
AN - SCOPUS:85107615474
SN - 2666-3546
VL - 8
JO - Brain, Behavior, and Immunity - Health
JF - Brain, Behavior, and Immunity - Health
M1 - 100126
ER -