Plasma L-Tryptophan Concentration in Major Depressive Disorder: New Data and Meta-Analysis

Objective: Tryptophan, an essential amino acid, is the precursor to serotonin and is metabolized mainly by the kynurenine pathway. Both serotonin and kynurenine have been implicated in the pathophysiology of major depressive disorder (MDD). However, plasma tryptophan concentration in patients with MDD has not unequivocally been reported to be decreased, which prompted us to perform a meta-analysis on previous studies and our own data. Data Sources: We searched the PubMed database for case-control studies published until August 31, 2013, using the search terms plasma AND tryptophan AND synonyms for MDD. An additional search was performed for the term amino acid instead of tryptophan. We obtained our own data in 66 patients with MDD (DSM-IV) and 82 controls who were recruited from March 2011 to July 2012. The majority of the patients were medicated (N = 53). Total plasma tryptophan concentrations were measured by the liquid chromatography/mass spectrometry method. Study Selection: We scrutinized 160 studies for eligibility. Original articles that were written in English and documented plasma tryptophan values in patients and controls were selected. Data Extraction: We included 24 studies from the literature and our own data in the meta-analysis, which involved a total of 744 patients and 793 controls. Data on unmedicated patients (N = 156) and their comparison subjects (N = 203) were also extracted. To see the possible correlation between tryptophan concentrations and depression severity, meta-regression analysis was performed for 10 studies with the Hamilton Depression Rating Scale 17-item version score. Results: In our case-control study, mean (SD) plasma tryptophan level was significantly decreased in the MDD patients versus the controls (53.9 [10.9] vs 57.2 [11.3] mu mol/L; P = .03). The meta-analysis after adjusting for publication bias showed a significant decrease in patients with MDD with a modest effect size (Hedges g, -0.45). However, analysis on unmedicated subjects yielded a large effect (Hedges g, -0.84; P = .00015). We found a weak association with depression severity in the meta-regression analysis (P = .049). Conclusions: This meta-analysis provides convincing evidence for reduced plasma tryptophan levels in patients with MDD, particularly in unmedicated patients.