Plasma Kynurenine Level is Associated With Left DLPFC Activity and Can Predict Treatment Response in Major Depressive Disorder

To establish treatment response biomarkers that reflect the pathophysiology of depression, it is important to use an integrated set of features that are promising as biomarkers. This study aimed to determine the relationship between blood metabolites related to treatment response to escitalopram and regional brain activity at rest and to find the characteristics of depression that respond to treatment. Blood metabolite levels and resting brain activity were measured in patients with depression (N = 65) before and after 6 weeks treatment with escitalopram and healthy controls (N = 36). Thirty-two patients (49.2%) showed clinical response (>50% reduction in Hamilton Rating Scale for Depression score) and were classified as Responders, and the remaining 33 patients were classified as Nonresponders. Pretreatment plasma kynurenine level and fractional amplitude of low-frequency fluctuations (fALFF) of the left dorsolateral prefrontal cortex (DLPFC) were lower in Responders, and their elevations after treatment were correlated with improvement in symptoms. Moreover, fALFF of the left DLPFC was significantly correlated with plasma kynurenine level in pretreatment patients with depression and healthy controls. Decreased kynurenine level and resting-state regional brain activity of the left DLPFC may be involved in the pathophysiology of depression in response to escitalopram treatment.