Depressed mood and cognitive functions in patients with cancer are associated with alterations in tryptophan metabolism

Rationale: Depression and cognitive deficits have been observed in patients with cancer. Although degradation of tryptophan (TRP; precursor of serotonin) has been detected in cancer, the exact association between whole body TRP metabolism and neuropsychological functions in advanced cancer remains unclear.
Methods: In 16 patients with solid tumours (C) and 16 age and gender matched healthy controls, the rates of appearance (Ra) and clearance of TRP were assessed by primed continuous infusion of L-[indole-2H5]TRP. Plasma amino acid profile was analyzed to measure plasma TRP level, and ratio plasma TRP to Large neutral amino acids (LNAA = sum of tyrosine, phenylalanine, isoleucine, leucine and valine) calculated as marker of TRP uptake into the brain. Mood was assessed by the
Hospital Anxiety and Depression Score, and cognition by a test battery consisting of the Auditory Verbal Learning, Verbal Fluency, Trail Making, and Stroop tests. Plasma amino acid levels and isotope enrichments were measured by LC-MS/MS. Statistics were done by unpaired t-tests and Pearson’s correlation.
Results: Depression scores were higher in C (5.0 vs 2.6, P<0.05), but cognitive outcomes were comparable between the groups. In C, the depression scores correlated negatively with plasma TRP (r=-0.69, P<0.01) and positively with TRP clearance rate (r=0.60, P<0.05). Additionally, we found that only in C, TRP Ra was associated with word fluency (r=0.70, P<0.01), processing speed (TMT completion time; r<-0.54, P<0.05), and verbal learning capacity and memory (immediate and delayed recall, learning rate and recognition; r≥0.63, P≤0.01). No relationship was found between plasma TRP/LNAA ratio and mood or cognition.
Conclusion: These findings suggest that an imbalance in TRP metabolism plays a role in the depressive symptoms in patients with cancer and may increase their risk of developing cognitive deficits.