Kynurenine pathway metabolites selectively associate with impaired associative memory function in depression.

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.

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© 2020 The Authors.

Déclaration de conflit d'intérêts

Authors MC, JC, IS, CC, SM, and PR have nothing to declare. RD has received honoraria from Pfizer USA and from Danone Nutricia Research France for work that is not related to the present study. MHT has received funds from Allergan, Alto Neuroscience Inc, Applied Clinical Intelligence LLC, Axsome Therapeutics, Boegringer Ingelheim, Engage Health Media, GreenLight VitalSign6 Inc, Janssen, 10.13039/501100013327Lundbeck Research 10.13039/100011408USA, 10.13039/100009947Merck Sharp & Dohme Corp., Navitor Pharmaceutical Inc, Otsuka, Perception Neuroscience, Pharmerit International, SAGE Therapeutics, and Signant Health for work consulting and/or advisory board service not related to the present study. He has received funds for editorial work from the 10.13039/100005386American Psychiatric Association. Dr. Toups has received funds for service on a Data, Safety and Monitory Board from Otsuka for work not related to the present study.