Kynurenine pathway changes in late-life depression with memory deficit

Abstract

Kynurenine pathway (KP) activation is associated with many neuropsychiatric diseases, such as major depressive disorder (MDD) and Alzheimer's disease (AD). Investigations conducted on MDD seldom shed light on KP changes in late-life depression (LLD), though memory deficit (MD) in patients with LLD is a predictable sign of AD. Thus, we aimed to investigate whether tryptophan (TRP) metabolism and kynurenine (KYN) metabolism were imbalanced in patients with LLD with MD and in patients with LLD without MD. We explored KP characteristics between LLD with MD and LLD without MD groups. We investigated 85 patients with LLD and MD, 71 patients with LLD without MD, and 129 healthy controls (HCs). Serum concentrations of TRP, KYN, and kynurenic acid (KYNA) were detected by liquid chromatography-tandem mass spectrometry. Cognition performance was assessed by the Mini-Mental State Examination (MMSE). Language ability was assessed by the Boston Naming Test (BNT). Depressive symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17). Lower TRP and KYNA levels, a lower KYNA/KYN ratio and a higher KYN/TRP ratio were found in patients with LLD and MD compared to those in HC. Low levels of TRP and KYN, in the absence of a changed KYN/TRP ratio, were found in patients with LLD without MD. The KYNA/TRP ratio and MMSE, BNT, and HAMD-17 scores were associated with the presence of LLD. MMSE scores and a trend for the KYN/TRP ratio were associated with the presence of MD in patients with LLD. Aside from MMSE scores, there was a trend toward an association between the KYN/TRP ratio and the presence of MD in patients with LLD. In conclusion, profound shifts in TRP metabolism and KYN metabolism were found in patients with LLD and MD but not in patients with LLD without MD.

Keywords: Kynurenic acid; Kynurenine; Late-life depression; Memory deficit; Tryptophan.