Luijendijk Maryse J, Tesselaar Margot E T, van Rossum Huub H, van Faassen Martijn, Korse Catharina M, Verbeek Wieke H M, Spruit Jocelyn R, Scheelings Pernilla C, Hooghiemstra Eva H, Kema Ido P, Ruhé Henricus G, Schagen Sanne B, de Vries Froukje E
Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Transl Psychiatry. 2025 May 21;15(1):176. doi: 10.1038/s41398-025-03272-z.
Cognitive and psychiatric problems are common in cancer patients, but literature on patients with neuroendocrine tumors (NET) is scarce. In a subset of these patients, the tumor produces serotonin, causing physical symptoms known as carcinoid syndrome. This peripheral overproduction of serotonin may cause central depletion of its precursor tryptophan, potentially resulting in cognitive and psychiatric problems. Therefore, we investigated cognitive and psychiatric function in patients with a serotonin overproduction and the association with this serotonin overproduction. Eighty-one patients with a serotonin-producing metastatic ileal NET underwent standardized neuropsychological and psychiatric assessment. Blood and urine samples were collected to determine concentrations of serotonin, its precursor tryptophan, and metabolite (5-HIAA). Multivariate normative comparison was applied to determine the prevalence of cognitive impairment. Separate linear regressions of serotonin, tryptophan, and 5-HIAA concentrations on cognitive function, depressive symptoms, and anxiety symptoms were performed, corrected for age, sex, education, and/or duration of illness. We found an 11% prevalence of cognitive impairment and a 20% prevalence of psychiatric disorders. Cognitive function was not related to measures of peripheral serotonin production. Unexpectedly, depressive symptoms were significantly associated with lower serum serotonin concentrations and elevated serum tryptophan concentrations. Cognitive symptoms of anxiety were also associated with elevated tryptophan concentrations. Concluding, cognitive or psychiatric problems occur in a minority of patients with NET and cannot be explained by tryptophan depletion following tumor-related serotonin production.
认知和精神问题在癌症患者中很常见，但关于神经内分泌肿瘤（NET）患者的文献却很稀少。在这些患者的一个亚组中，肿瘤会产生血清素，导致类癌综合征等身体症状。血清素的这种外周过量产生可能会导致其前体色氨酸的中枢性消耗，从而可能导致认知和精神问题。因此，我们研究了血清素过量产生的患者的认知和精神功能，以及与这种血清素过量产生的关联。81例产生血清素的转移性回肠NET患者接受了标准化的神经心理学和精神评估。采集血液和尿液样本以测定血清素、其前体色氨酸和代谢物（5-羟吲哚乙酸）的浓度。应用多变量规范比较来确定认知障碍的患病率。对血清素、色氨酸和5-羟吲哚乙酸浓度与认知功能、抑郁症状和焦虑症状进行了单独的线性回归分析，并对年龄、性别、教育程度和/或病程进行了校正。我们发现认知障碍的患病率为11%，精神障碍的患病率为20%。认知功能与外周血清素产生的指标无关。出乎意料的是，抑郁症状与较低的血清血清素浓度和升高的血清色氨酸浓度显著相关。焦虑的认知症状也与色氨酸浓度升高有关。总之，少数NET患者会出现认知或精神问题，且不能用肿瘤相关血清素产生后色氨酸耗竭来解释。
