Kynurenine pathway changes in late-life depression with memory deficit

Area of Science:

• Neuroscience
• Metabolic Psychiatry
• Geriatric Psychiatry

Background:

• Kynurenine pathway (KP) activation is linked to neuropsychiatric disorders like major depressive disorder (MDD) and Alzheimer's disease (AD).
• Late-life depression (LLD) with memory deficits (MD) may indicate early AD, yet KP changes in LLD are understudied.
• Understanding tryptophan (TRP) and kynurenine (KYN) metabolism is crucial for differentiating LLD subtypes.

Purpose of the Study:

• To investigate imbalances in TRP and KYN metabolism in patients with LLD with MD versus LLD without MD.
• To explore KP characteristics differentiating these LLD patient groups from healthy controls (HCs).
• To assess the association of metabolic profiles with cognitive and depressive symptoms.

Main Methods:

• Serum concentrations of TRP, KYN, and kynurenic acid (KYNA) were measured using liquid chromatography-tandem mass spectrometry.
• Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and Boston Naming Test (BNT).
• Depressive symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17) in 85 LLD with MD, 71 LLD without MD, and 129 HCs.

Main Results:

• Patients with LLD and MD exhibited lower TRP and KYNA, a lower KYNA/KYN ratio, and a higher KYN/TRP ratio compared to HCs.
• Patients with LLD without MD showed low TRP and KYN levels but no significant change in the KYN/TRP ratio.
• The KYNA/TRP ratio and MMSE, BNT, and HAMD-17 scores correlated with LLD presence; MMSE scores and KYN/TRP ratio showed association with MD in LLD.

Conclusions:

• Profound alterations in TRP and KYN metabolism characterize LLD with memory deficits.
• LLD without memory deficits does not display the same significant metabolic disturbances.
• These findings suggest distinct pathophysiological mechanisms underlying LLD subtypes and their cognitive impact.