Tryptophan breakdown and cognition in bipolar disorder

Area of Science:

• Neuroscience
• Psychiatry
• Biochemistry

Background:

• Bipolar disorder (BD) is frequently associated with cognitive deficits, affecting memory, attention, and executive functions.
• These deficits persist across mood states, including euthymia.
• Chronic neuroinflammation is hypothesized to underlie these cognitive impairments in BD.

Purpose of the Study:

• To investigate the association between serum levels of kynurenine and its metabolites and cognitive function in individuals with BD.
• To explore the role of the kynurenine pathway, an inflammatory marker, in cognitive performance in BD.

Main Methods:

• Sixty-eight euthymic individuals with BD and 93 healthy controls underwent cognitive testing.
• Serum levels of kynurenine, 3-hydroxykynurenine, and kynurenic acid were analyzed.
• Ratios of these metabolites were calculated and correlated with cognitive performance.

Main Results:

• In male participants with BD, higher 3-hydroxykynurenine to kynurenic acid ratios correlated with poorer verbal memory (CVLT performance).
• The kynurenine to 3-hydroxykynurenine ratio also showed an association with a verbal memory sub-score in males with BD.
• These associations were not observed in female participants with BD or in the control group.

Conclusions:

• A shift towards the 3-hydroxykynurenine arm of the kynurenine pathway may contribute to memory deficits in males with BD.
• These findings implicate central inflammatory processes, mediated by the kynurenine pathway, in the cognitive dysfunction observed in bipolar disorder.