NIMG-37IMAGING CEREBRAL TRYPTOPHAN METABOLISM IN BRAIN TUMOR-ASSOCIATED DEPRESSION

BACKGROUND: Depression is a common co-morbidity in patients with brain tumors, but its pathophysiology remains poorly understood. Abnormal metabolism of tryptophan, a precursor of serotonin and kynurenine, may play a role in tumor-associated depression. We used alpha-[11C]methyl-L-tryptophan (AMT) PET to evaluate if depression in patients with brain tumors is associated with altered tryptophan metabolism in the tumor and/or contralateral unaffected brain regions. METHODS: Twenty-one patients (mean age: 57 years) with brain tumors (n = 10 meningioma, n = 8 glioma, n = 3 brain metastases) underwent MRI and AMT-PET scanning. All patients were screened for depression using the Beck Depression Inventory-II (BDI-II). None of them were on antidepressant medication. Tryptophan kinetic parameters, including AMT K (unidirectional uptake) and volume of distribution (VD, an estimate of net tryptophan transport) were calculated from dynamic AMT-PET data using Patlak graphical analysis within the tumor and in contralateral cortical and subcortical regions. Depression scores were correlated with AMT-PET variables using Spearman's rank correlation. PET values of depressed vs. non-depressed patients were also compared (Mann-Whitney U test). RESULTS: Seven patients (33%) showed BDI-II scores consistent with depression: 5 had severe/moderate and 2 had mild depression. Depression scores showed a positive correlation with thalamic and temporal cortex K values (r = 0.63 p = 0.004; r = 0.46 p = 0.048, respectively), while cognitive-affective subscores positively correlated with thalamic K (p = 0.03), as well as striatal (p = 0.006) and frontal cortical VD (p = 0.046). Depression scores did not correlate with tumoral PET variables. Both frontal cortical and striatal AMT VD values were higher in depressed than non-depressed patients (p = 0.017 and p = 0.036, respectively). CONCLUSIONS: Tryptophan metabolic abnormalities in non-tumoral brain regions, such as thalamus, striatum and frontal cortex, are associated with depression in patients with brain tumors. These PET abnormalities support the notion that an imbalance between the serotonin and kynurenine pathways of cerebral tryptophan metabolism may play a role in brain tumor-associated depression.