Abstract # 1755 Sleep disturbance and kynurenine metabolism in a group of currently depressed, previously depressed, and never depressed subjects

Abstract

Sleep disturbance is known to increase inflammation. Inflammation may activate the kynurenine metabolic pathway and increase the synthesis of potentially neurotoxic metabolites such as 3-hydroxykynurenine (3HK) and quinolinic acid (QA), relative to kynurenic acid (KynA). However, the associations between sleep disturbance and kynurenine metabolism have not been examined. This study examined such associations in a group of 68 currently depressed, 26 previously depressed, and 66 never depressed subjects (total N = 160). All subjects were unmedicated and interviewed with the Structured Clinical Interview for DSM-IV-TR. Sleep disturbance was assessed using the Pittsburgh Sleep Quality Index. Serum concentrations of kynurenine metabolites were measured using high performance liquid chromatography. Neuroprotective indices of kynurenine metabolites, the primary outcome variables, were calculated as KynA/3HK and KynA/QA. Sleep disturbance was inversely correlated with KynA/3HK (r = −0.24, p = 0.002) and KynA/QA (r = −0.22, p = 0.005). The association between sleep disturbance and KynA/QA remained significant even after adjusting for age, sex, body-mass index, diagnosis, and depressive symptoms (adjusted beta −0.31, p = 0.02). This study is the first to demonstrate an association between sleep disturbance and a neurotoxic profile of kynurenine metabolism. Sleep disturbance is a well-known risk factor for depression, and inflammation has been suggested as a potential mechanism of this association. Thus, kynurenine metabolism, increasingly recognized as a potential pathway linking inflammation to depression, may be an underlying mechanism of the connection among sleep disturbance, inflammation, and depression.