Kynurenine pathway changes in late-life depression

Abstract

Background: Kynurenine pathway (KP) activation is associated with several neuropsychiatric diseases, including major depression disorder (MDD). Although several investigations have been conducted on MDD, these have seldom shed light on KP changes in late-life depression (LLD).

Objective: We aimed to investigate whether tryptophan (TRP) metabolism and kynurenine (KYN) metabolism are imbalanced in LLD patients and to explore the differences in KP characteristics between early onset depression (EOD) and late onset depression (LOD) patients.

Methods: We investigated 170 LLD patients (EOD 90, LOD 80) and 135 normal controls. Serum concentrations of TRP, KYN and kynurenic acid (KYNA) were detected by the liquid chromatography-tandem mass spectrometry method. Depressive symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17).

Results: LLD patients exhibited lower levels of TRP, KYN, KYNA and KYNA/KYN ratio and a higher level of KYN/TRY ratio than normal controls. The decrease in TRP and the increase in KYN/TRP ratio were found in LOD patients. A low TRP level without increased KYN/TRP ratio was found in EOD patients. The "Depression" factor, which was extracted from HAMD-17 by the principal component factor analysis, was correlated with the TRP level and KYNA/KYN ratio in the EOD group, but no such correlation was found in the LOD group.

Conclusions: KP changes were observed in LLD patients; LOD patients showed profound shifts in TRP metabolism, while EOD patients showed low TRP level and a shift in KYN metabolism.

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