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

Barbara S Van der Meij, C. K. Lieben, Nicolaas E P Deutz, Ramon E. Rodriguez, Fari Koeman, Tiffany Smit, Marielle Engelen

Research output: Contribution to journalMeeting AbstractResearchpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)S70
Number of pages1
JournalClinical Nutrition
Volume36
Issue numberS1
DOIs
Publication statusPublished - Sep 2017
EventThe 39th European Society for Clinical Nutrition and Metabolism Congress 2017 - Hague, Netherlands
Duration: 9 Sep 201712 Sep 2017
Conference number: 39
http://www.espen.org/congress/next-congresses/12-espen/index.php?option=com_content&view=article&id=214&Itemid=1052

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Tryptophan
Cognition
Depression
Verbal Learning
Neoplasms
Trail Making Test
Stroop Test
Neutral Amino Acids
Amino Acids
Isoleucine
Valine
Phenylalanine
Short-Term Memory
Leucine
Tyrosine
Serotonin
Anxiety
Learning
Brain

Cite this

Van der Meij, Barbara S ; Lieben, C. K. ; Deutz, Nicolaas E P ; Rodriguez, Ramon E. ; Koeman, Fari ; Smit, Tiffany ; Engelen, Marielle. / Depressed mood and cognitive functions in patients with cancer are associated with alterations in tryptophan metabolism. In: Clinical Nutrition. 2017 ; Vol. 36, No. S1. pp. S70.
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abstract = "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 theHospital 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.",
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Depressed mood and cognitive functions in patients with cancer are associated with alterations in tryptophan metabolism. / Van der Meij, Barbara S; Lieben, C. K. ; Deutz, Nicolaas E P; Rodriguez, Ramon E.; Koeman, Fari; Smit, Tiffany; Engelen, Marielle.

In: Clinical Nutrition, Vol. 36, No. S1, 09.2017, p. S70.

Research output: Contribution to journalMeeting AbstractResearchpeer-review

TY - JOUR

T1 - Depressed mood and cognitive functions in patients with cancer are associated with alterations in tryptophan metabolism

AU - Van der Meij, Barbara S

AU - Lieben, C. K.

AU - Deutz, Nicolaas E P

AU - Rodriguez, Ramon E.

AU - Koeman, Fari

AU - Smit, Tiffany

AU - Engelen, Marielle

PY - 2017/9

Y1 - 2017/9

N2 - 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 theHospital 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.

AB - 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 theHospital 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.

U2 - 10.1016/S0261-5614(17)30580-0

DO - 10.1016/S0261-5614(17)30580-0

M3 - Meeting Abstract

VL - 36

SP - S70

JO - Clinical Nutrition

JF - Clinical Nutrition

SN - 0261-5614

IS - S1

ER -