The Glutamate System in Depression Quinolinic Acid as a Depressiogenic Substance

The Glutamate System in Depression Quinolinic Acid as a Depressiogenic Substance 

Apart fi om certain liver cells, only macrophage derived cells are able to convert tryptophan into quinolonic acid (Saito et al., 1993). Interestingly, in a model of infection, the highest concentrations of quinolinic acid are found in the gray and white matter of the cortex, notin subcortical areas. High levels of quinolinic acid therefore may lead to cortical dysfunction (Heyes et al., 1998). 

The strong association between cortical quinolinic acid concentrations and local IDO activity supports the view that the induction of IDO is an important event in initiating the increase of quinolinic acid production (Heyes et al., 1992). In the CNS, invaded macrophages and microglial cells are able to produce quinolinic acid (Saito et al., 1993). Peripheral immune stimulation, however, under certain conditions also leads to increased CNS concentration of quinolinic acid (Saito et al., 1993). During a local inflammatory CNS process, the quinolinic acid production in the CNS increases without changes of the blood-levels of quinolinic acid. While the local quinolinic acid production correlates with the level of B2 microglobulin, an inflammatory marker. Local CNS concentrations of quinolinic acid are able to far exceed the blood levels (Heyes et al., 1998). 

A recent study showed that depressive symptoms are related to an increased ratio of KYN/KYNA in depression (Wichers et al., 2005). The increase of this ratio reflects that in depressed states KYN is preferentially metabolized to quinolinic acid— w hile the KYNA pathway is neglected. Therefore the preferred metabolism to quinolinic acid—but not the KYNA metabolism—is associated with more pronounced depressive symptoms. 

An increase of quinolinic acid is strongly associated with several prominent features of depression decrease in reaction time (Martin et al., 1992, 1993 Heyes et al., 1991) and cognitive deficits, in particular difficulties in learning (Heyes et al., 1998). In an animal model, an increase of quinolinic acid and 3-hydroxykynurenine was associated with anxiety (Lapin, 2003). 

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