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Tryptophan Lowered Without Tryptophan Catabolite Pathway Activation in MDD, BD
Total and free tryptophan, as well as the tryptophan/competing amino-acids ratio, were lower in people with major depressive disorder (MDD) and bipolar disorder (BD) compared with control subjects, according to a systematic review and meta-analysis published online in Brain, Behavior, & Immunity – Health.
“Our findings suggest that MDD and BD are accompanied by tryptophan depletion without indoleamine 2,3-dioxygenase (IDO) and tryptophan catabolite pathway activation,” researchers wrote. “Lowered tryptophan availability is probably the consequence of lowered serum albumin during the inflammatory response in affective disorders.”
The review included 121 full-text articles and 15,470 people. Among them, 8024 were patients with MDD and BD, and 7446 were healthy controls.
The significantly decreased tryptophan levels and tryptophan/competing amino-acids ratio in patients with MDD and BD identified in the analysis had a moderate effect size, according to the study. Additionally, the analysis showed lower kynurenine levels in patients with MDD and BD compared with healthy control subjects, although the effect size was small. The reported differences were significant in plasma but not in serum or the central nervous system.
Additionally, researchers found unaltered or even lowered kynurenine/tryptophan ratio and neurotoxicity indices based on downstream tryptophan catabolites in patients with MDD and BD. The kynurenine/tryptophan ratio is often used as an index of IDO activity.
“IDO enzyme activity did not exhibit signs of hyperactivity, as indicated by the patients’ lowered kynurenine levels and an unchanged kynurenine/tryptophan ratio,” researchers wrote. “Moreover, there is no evidence that MDD and BD are accompanied by increased neurotoxicity due to an activated tryptophan catabolite pathway.”
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