Kynurenine Pathway Metabolites and Executive Function Impairments in Generalized Anxiety Disorder: A Case Control...

Area of Science:

• Neuroscience
• Biochemistry
• Psychiatry

Background:

• Generalized anxiety disorder (GAD) is characterized by excessive worry and cognitive deficits.
• The underlying neurometabolic mechanisms of GAD, particularly involving the kynurenine pathway, remain incompletely understood.

Purpose of the Study:

• To investigate the relationship between kynurenine pathway metabolites and cognitive function in patients with GAD.
• To identify potential biomarkers for GAD.

Main Methods:

• Neuropsychological tests (WCST, TMT-A/B, DST, VFT, Stroop) were administered to 41 GAD patients and 41 healthy controls (HC).
• Blood samples were analyzed for kynurenine pathway metabolites (KYNA, QUIN, TRP, 3-HK, KYN, 3-HAA) using LC-MS.
• Statistical analyses, including correlation and logistic regression, were performed.

Main Results:

• GAD patients exhibited significant deficits in executive function and attention compared to HC.
• GAD patients had elevated QUIN levels and reduced KYNA/QUIN ratios.
• A higher KYNA/QUIN ratio was independently associated with lower odds of GAD.

Conclusions:

• Dysregulation of the kynurenine pathway, specifically elevated QUIN and a reduced KYNA/QUIN ratio, is implicated in the executive dysfunction observed in GAD.
• The KYNA/QUIN ratio shows promise as a potential biomarker and therapeutic target for GAD.