P14.57 Association of tryptophan metabolism and depression in patients with primary brain tumors

Abstract

Abstract BACKGROUND Patients with brain tumor have an increased risk for depressive disorder, whose underlying pathomechanism may involve dysregulated tryptophan/kynurenine metabolism. In this study, we analyzed the relation of depression to cerebral and systemic tryptophan metabolism in patients with primary brain tumors. MATERIAL AND METHODS Thirty-four patients with newly-diagnosed (n=19) or recurrent (n=15) primary brain tumors (25 gliomas, 8 meningiomas, 1 dysembryoplastic neuroepithelial tumor) underwent pre-treatment alpha-[11C]methyl-L-tryptophan (AMT)-PET and completed the Beck Depression Inventory-II (BDI-II) questionnaire. MRI and AMT-PET images were co-registered, and AMT K values (estimate of unidirectional tryptophan uptake, related to tryptophan metabolism) were measured in contralateral non-tumoral cortical and subcortical regions and correlated with BDI-II total and subscale (cognitive, affective, and somatic) scores. In a subset of 28 patients, plasma tryptophan metabolite levels were also measured and correlated with BDI-II scores. RESULTS In the whole group (n=34), 35% of the patients (n=12) had BDI-II scores indicating depression, while only a minority of them (n=5) were treated with selective serotonin reuptake inhibitors (SSRI). No difference was observed in AMT K values between gliomas vs. non-gliomas or between newly-diagnosed vs. recurrent tumors. Frontal cortical and thalamic AMT K values positively correlated with BDI-II total and somatic subscale scores (r=0.49, p=0.004 and r=0.53, p=0.001, respectively), and these correlations became stronger when patients with SSRI treatment were excluded. Levels of plasma tryptophan and its metabolites were not different between gliomas vs. non-gliomas, newly-diagnosed vs. recurrent tumor nor depressed vs. non-depressed patients. SSRI treatment showed no effect on plasma tryptophan metabolite levels. No correlation was found between depression and plasma tryptophan and its metabolite levels. CONCLUSION While plasma levels of tryptophan metabolites are not associated with depressive symptoms, higher tryptophan metabolism in the frontal cortex and thalamus, measured by PET, may serve as an imaging biomarker of brain tumor-associated depression and supports the role of dysregulated tryptophan/kynurenine metabolism in this condition.