Abstract
Patients with brain tumors have an increased risk for depression, whose underlying pathomechanism may involve dysregulated tryptophan/kynurenine metabolism. In this study, we analyzed the relation of depressive symptoms to clinical and tumor characteristics as well as cerebral and systemic tryptophan metabolism in patients with primary brain tumors. Sixty patients with newly-diagnosed or recurrent primary brain tumor underwent testing with the Beck Depression Inventory-II (BDI-II), and 34 patients also had positron emission tomography (PET) imaging with alpha-[11C]methyl-L-tryptophan (AMT). BDI-II scores were correlated with clinical and tumor-related variables, cerebral regional AMT metabolism measured in the non-tumoral hemisphere, and plasma tryptophan metabolite levels. Sixteen patients (27%) had BDI-II scores indicating depression, including 6 with moderate/severe depression. High BDI-II scores were independent of clinical and tumor-related variables except lower Karnofsky Performance Status scores. In patients with recurrent malignant gliomas, depression was associated with shorter survival (hazard ratio: 3.7; p = 0.048). High BDI-II total and somatic subscale scores were associated with higher frontal cortical and thalamic AMT metabolic values measured on PET. In contrast, plasma tryptophan and kynurenine metabolite levels did not correlate with the BDI-II scores. In conclusion, our results confirm previous data that depression affects more than ¼ of patients with primary brain tumors, it is largely independent of tumor characteristics and is associated with shorter survival in patients with recurrent malignant gliomas. On PET imaging, higher tryptophan metabolism in the frontal cortex and thalamus was found in those with brain tumor-associated depression and supports the role of dysregulated tryptophan/kynurenine metabolism in this condition.
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Acknowledgements
We thank Edit Bosnyák, MD, PhD, who assisted in data collection. We are grateful to the entire staff at the PET Center, Children’s Hospital of Michigan, Detroit Medical Center, who provided invaluable technical help in patient scheduling and performing the PET scans. We also thank Thomas Mangner, PhD, who performed the AMT radiosynthesis, as well as Xun Bao and Jing Li, PhD, at the Karmanos Cancer Institute Pharmacology Core for performing the blood tryptophan metabolite measurements.
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This study was supported by grants from the National Cancer Institute (R01 CA123451 and P30 CA022453).
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John, F., Michelhaugh, S.K., Barger, G.R. et al. Depression and tryptophan metabolism in patients with primary brain tumors: Clinical and molecular imaging correlates. Brain Imaging and Behavior 15, 974–985 (2021). https://doi.org/10.1007/s11682-020-00305-7
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DOI: https://doi.org/10.1007/s11682-020-00305-7