Plasma Anthranilic Acid and Leptin Levels Predict HAM-D Scores in Depressed Women

OBJECTIVES: Major depressive disorder (MDD) is associated with dysregulations of leptin and tryptophan-kynurenine (Trp-Kyn) (TKP) pathways. Leptin, a pro-inflammatory cytokine, activates Trp conversion into Kyn. However, leptin association with down-stream Kyn metabolites in MDD is unknown. METHODS: Fasting plasma samples from 29 acutely ill drug-naive (n = 16) or currently non-medicated (>= 6 weeks; n = 13) MDD patients were analyzed for leptin, Trp. Kyn, its down-stream metabolites (anthranilic [AA], kynurenic [KYNA], xanthurenic [XA] acids and 3-hydroxykynurenine [3HK]), C-reactive protein (CRP), neopterin, body mass index (BMI). and insulin resistance (HOMA-IR). Depression severity was assessed by HAM-D-21. RESULTS: In female (n = 14) (but not in male) patients HAM-D-21 scores correlated with plasma levels of AA (but not other Kyn metabolites) (rho = -0.644, P = .009) and leptin (Spearman's rho = -0.775, P = .001). Inclusion of AA into regression analysis improved leptin prediction of HAM-D from 48.5% to 65.9%. Actual HAM-D scores highly correlated with that calculated by formula: HAM-D = 34.8518-(0.5660 x leptin [ng/ml] + 0.4159 x AA [nmol/I]) (Rho = 0.84, P = .00015). In male (n = 15) (but not in female) patients leptin correlated with BMI. waist circumference/hip ratio, CRP, and HOMA-IR. CONCLUSIONS: Present findings of gender specific AA/Leptin correlations with HAM-D are important considering that AA and leptin are transported from plasma into brain, and that AA formation is catalyzed by kynureninase-the only TKP gene associated with depression according to genome-wide analysis. High correlation between predicted and actual HAM-D warrants further evaluation of plasma AA and leptin as an objective laboratory test for the assessment of depression severity in female MDD patients

Automated summary

This study found a negative correlation between plasma levels of anthranilic acid (AA) and HAM-D-21 scores in female MDD patients, and that inclusion of AA improved leptin's prediction of depression severity. In male patients, leptin was correlated with BMI, waist circumference/hip ratio, CRP, and HOMA-IR.