Kynurenines are altered in the brain in depression, in a subgroup dependent manner: Implications for targeted treatment approaches.

Major depressive disorder (MDD) is a complex and multi-faceted disorder with a high level of heterogeneity at both the clinical and molecular level. Emerging evidence suggests a significant role of the kynurenine pathway in MDD neurobiology that may be associated with specific subgroups. In a recent study, we examined the kynurenine pathway in postmortem anterior cingulate cortex tissue obtained from subjects with and without MDD. We identified significant changes in MDD that were associated with sex and suicide but found minimal changes in the kynurenine pathway when grouping our cohort as a general classification of MDD. Furthermore, we identified significant correlations between age and quinolinic acid that were specific to MDD. In this commentary, we discuss the importance of considering a range of subgroups in the design and analysis of molecular studies in psychiatric disorders. Future studies should examine the extent of subgroup-specific changes to advance our understanding of MDD and explore targeted therapeutic approaches designed to address the specific changes in these subgroups.