the purine, tyrosine, and tryptophan pathways, as well as tocopherols. Several metabolites purchase RS1 changed significantly from baseline to four weeks in the placebo group. Changes in absolute concentrations of metabolites after four week are shown; positive values up-regulated metabolites, negative values downregulated metabolites. Significant changes are shown in bold. See methods section for the details of statistical analysis. Abbreviations: 5-MTPM 25-methoxytryptamine; for the remaining metabolites, see Analysis of Tryptophan Pathway and Treatment Outcome Analysis of metabolic changes that correlates with treatment outcome suggests that different branches within tryptophan metabolism might be regulated differently in responders and non-responders to drug and to placebo. Therefore we performed more targeted and comprehensive 12490620 analysis of the tryptophan pathway, with a focus on the methoxyindole and KYN branches in responders and non-responders to sertraline and placebo. Correlations between baseline levels of individual metabolites, as well as the ratios of individual metabolites within and among branches of tryptophan pathway, and four weeks treatment outcome were evaluated. The ratios between levels of individual metabolites could provide insights about enzymes that are regulated differently in responders and non-responders. The ratios of metabolites across branches 
of tryptophan metabolism could provide insights about a shift in utilization of substrates for different branches of tryptophan pathway. The strongest ratio correlations with outcome were for 5-MTPOL/TRP, 5-MTPM/5-MTPOL, 5-MTPM/5-HT, and 5-MTPOL/5-HTP, although only the first one reached a conventional level of significance. Analyses of change in responders and non-responders to placebo revealed that there were significant four week increases in 5-MTPOL and MEL in responders to placebo, a pattern that was similar to that seen in the good responders in the sertraline treatment condition. However, 5-MTPM was not significantly changed in good responders to placebo. There were no significant changes observed in the group of poor responders to placebo. There were also significant pre- to post-treatment decreases in the KYN/MEL and 3-OHKY/MEL ratios among good responders to placebo. As with sertraline, good responders to placebo show a shift in tryptophan metabolism from KYN production towards the production of MEL. Tyrosine Pathway and Treatment Outcome. Correlating pre-treatment metabolite levels to the four-week treatment outcome did not yield any metabolites within the tyrosine pathway that significantly correlate with response to treatment with drug or placebo. An examination of changes in metabolites in responders and non-responders in the sertraline group yielded 4-HPAC and DIOHMAL to be significantly increased in responders. DIOHMAL levels were also significantly increased over the four week period in the non-responders. Significant increases 11078888 in LD and HGA levels after four weeks were evident in the group showing poor response to sertraline. In the placebo group HGA was increased in nonresponders and none of the other metabolites on the tyrosine pathway were significantly changed in this treatment group. Note: A positive correlation coefficient indicates that responders favor higher ratios. Abbreviations: 5-MTPM = 5-methoxytryptamine. For the remaining metabolites, see Discussion The results of our recent metabolomics study indicated that pretreatment serum metabolic signatur
