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Imaging cerebral tryptophan metabolism in brain tumor-associated depression.

Bosnyák E, Kamson DO, Behen ME, Barger GR, Mittal S, Juhász C - EJNMMI Res (2015)

Bottom Line: High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman's rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004).Frontal and striatal VD' values were higher in the depressed subgroup than in non-depressed patients (p < 0.05); the group difference was even more robust when moderately/severely depressed patients were compared to patients with no/mild depression (frontal: p = 0.005; striatal: p < 0.001).Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Wayne State University, 3901 Beaubien Street, Detroit, MI, 48201, USA. drbosnyakedit@gmail.com.

ABSTRACT

Background: Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumor-associated depression. Our recent studies with alpha[(11)C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression.

Methods: Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD', an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables.

Results: The mean BDI-II score was 12 ± 10 (range: 2-33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman's rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004). Frontal and striatal VD' values were higher in the depressed subgroup than in non-depressed patients (p < 0.05); the group difference was even more robust when moderately/severely depressed patients were compared to patients with no/mild depression (frontal: p = 0.005; striatal: p < 0.001). Tumor size, grade, and tumor type were not related to depression scores.

Conclusions: Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of brain tumor-associated depression.

Trial registration: ClinicalTrials.gov NCT02367469.

No MeSH data available.


Related in: MedlinePlus

Comparison of AMT-PET variables in patients with no/mild depression vs. moderate/severe depression. Frontal and striatal AMT volume of distribution (VD’) values were significantly higher in patients with moderate/severe depression (frontal VD’: 0.43 vs. 0.31, p = 0.005; striatal VD’: 0.61 vs. 0.35, p < 0.001)
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Fig3: Comparison of AMT-PET variables in patients with no/mild depression vs. moderate/severe depression. Frontal and striatal AMT volume of distribution (VD’) values were significantly higher in patients with moderate/severe depression (frontal VD’: 0.43 vs. 0.31, p = 0.005; striatal VD’: 0.61 vs. 0.35, p < 0.001)

Mentions: In the whole group, the BDI-II depression scores showed a significant positive correlation with thalamic and temporal cortical K values, with the most robust correlations found for the thalamic values (r = 0.63; p = 0.004), that remained significant even after Bonferroni correction for multiple correlations (Additional file 1: Table S1, Fig. 2). In comparison of depressed (n = 7) vs. not depressed patients, frontal and striatal VD’ values were significantly higher in the depressed subgroup (0.40 ± 0.10 vs. 0.31 ± 0.06, p = 0.017 and 0.53 ± 0.19 vs. 0.36 ± 0.07, p = 0.035, respectively). The difference was even more robust when moderately/severely depressed patients (n = 5) were compared to patients with no/mild depression (frontal VD’: 0.43 ± 0.10 vs. 0.31 ± 0.06, p = 0.005; striatal VD’: 0.61 ± 0.16 vs. 0.35 ± 0.07, p < 0.001) (Fig. 3). Tumor size, tumor grade (in the primary brain tumors), tumor type, tumoral AMT-PET variables, and AMT SUVs in any structures were not related to the depression scores.Fig. 2


Imaging cerebral tryptophan metabolism in brain tumor-associated depression.

Bosnyák E, Kamson DO, Behen ME, Barger GR, Mittal S, Juhász C - EJNMMI Res (2015)

Comparison of AMT-PET variables in patients with no/mild depression vs. moderate/severe depression. Frontal and striatal AMT volume of distribution (VD’) values were significantly higher in patients with moderate/severe depression (frontal VD’: 0.43 vs. 0.31, p = 0.005; striatal VD’: 0.61 vs. 0.35, p < 0.001)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608955&req=5

Fig3: Comparison of AMT-PET variables in patients with no/mild depression vs. moderate/severe depression. Frontal and striatal AMT volume of distribution (VD’) values were significantly higher in patients with moderate/severe depression (frontal VD’: 0.43 vs. 0.31, p = 0.005; striatal VD’: 0.61 vs. 0.35, p < 0.001)
Mentions: In the whole group, the BDI-II depression scores showed a significant positive correlation with thalamic and temporal cortical K values, with the most robust correlations found for the thalamic values (r = 0.63; p = 0.004), that remained significant even after Bonferroni correction for multiple correlations (Additional file 1: Table S1, Fig. 2). In comparison of depressed (n = 7) vs. not depressed patients, frontal and striatal VD’ values were significantly higher in the depressed subgroup (0.40 ± 0.10 vs. 0.31 ± 0.06, p = 0.017 and 0.53 ± 0.19 vs. 0.36 ± 0.07, p = 0.035, respectively). The difference was even more robust when moderately/severely depressed patients (n = 5) were compared to patients with no/mild depression (frontal VD’: 0.43 ± 0.10 vs. 0.31 ± 0.06, p = 0.005; striatal VD’: 0.61 ± 0.16 vs. 0.35 ± 0.07, p < 0.001) (Fig. 3). Tumor size, tumor grade (in the primary brain tumors), tumor type, tumoral AMT-PET variables, and AMT SUVs in any structures were not related to the depression scores.Fig. 2

Bottom Line: High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman's rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004).Frontal and striatal VD' values were higher in the depressed subgroup than in non-depressed patients (p < 0.05); the group difference was even more robust when moderately/severely depressed patients were compared to patients with no/mild depression (frontal: p = 0.005; striatal: p < 0.001).Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Wayne State University, 3901 Beaubien Street, Detroit, MI, 48201, USA. drbosnyakedit@gmail.com.

ABSTRACT

Background: Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumor-associated depression. Our recent studies with alpha[(11)C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression.

Methods: Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD', an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables.

Results: The mean BDI-II score was 12 ± 10 (range: 2-33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman's rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004). Frontal and striatal VD' values were higher in the depressed subgroup than in non-depressed patients (p < 0.05); the group difference was even more robust when moderately/severely depressed patients were compared to patients with no/mild depression (frontal: p = 0.005; striatal: p < 0.001). Tumor size, grade, and tumor type were not related to depression scores.

Conclusions: Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of brain tumor-associated depression.

Trial registration: ClinicalTrials.gov NCT02367469.

No MeSH data available.


Related in: MedlinePlus