Major depressive disorder (MDD) is a serious psychiatric disorder, affecting over 264 million people globally. Despite its devastating and widespread burden, our current understanding of MDD neurobiology is limited.
Evidence, largely obtained from peripheral studies, suggests that alterations in the kynurenine pathway (KP) contribute to the aetiology of MDD. However, whether this dysfunction is present in the brain in MDD is unclear. Furthermore, kynurenine metabolites interact with the glutamatergic system , which is also proposed to be dysfunctional in MDD.
Given the ability of the kynurenine metabolites to modulate glutamatergic signalling, the interplay between these two systems is important to elucidate. Therefore, this thesis investigated the KP and rel ated glutamatergic markers in the anterior cingulate cortex in MDD, with a focus on identifying subgroup specific alterations, predominately utilising human postmortem brain tissues.
Collectively, this presentation will highlight novel insights into the dysregulation of the KP and the glutamatergic system in MDD. This work has built on the limited data from postmortem MDD studies and revealed for the first time, molecular evidence in the brain of subgroup specific changes in the KP in MDD. Overall, these findings reiterate the importance of subgroup approaches to enhancing our understanding of psychiatric disorders including MDD.