Elevated tumor necrosis factor-alpha receptor subtype 1 and the association with abnormal brain function in treatment-resistant depression.

Abstract

BACKGROUND:

Major depressive disorder (MDD) patients have shown elevated plasma levels of pro-inflammatory biomarkers compared to healthy controls. We hypothesized increased serum tumor necrosis factor-alpha receptor subtype 1 (TNF-α R1) is more associated with impaired brain function in patients with treatment-resistant depression (TRD) than those without TRD.

METHODS:

34 MDD patients and 34 healthy subjects were recruited and we separated MDD patients to TRD group (n = 20) and non-TRD (n = 14) group. Pro-inflammatory cytokines were assessed by enzyme-linked immunosorbent assays. A standardized uptake values (SUV) of glucose metabolism measured by 18F-FDG positron-emission-tomography (PET) was applied to all subjects for subsequent region-of- interest analyses and whole-brain voxel-wise analyses. 18F-FDG-PET measures glucose uptake into astrocytes in response to glutamate release from neuronal cells, and was thus used as a proxy measure to quantify glutamatergic neurotransmission in the human brain.

RESULTS:

Post-hoc analysis revealed that TRD group had higher serum concentrations of TNF-α R1 compared to healthy control or non-TRD group. In the MDD group, higher serum concentrations of TNF-α R1 significantly correlated with decreased SUV in anterior cingulate cortex (ACC) and bilateral caudate nucleus. The ROI analysis further supported the negative correlations of plasma TNF-α R1 and SUV in the ACC and caudate nucleus. Such correlation is more consistent in TRD group than in non-TRD and HC groups.

LIMITATION:

Glutamate neurotransmission and the effect of chronic stress on glutamate release in the brain were not measured directly.

CONCLUSIONS:

Increased TNF-α R1 was associated with impaired glutamatergic neurotransmission of caudate nucleus and ACC in MDD patients, particularly in the TRD.

• Authors: Mao-Hsuan Huang, Mu-Hong Chen, Pei-Chi Tu, Ya Mei Bai, Tung-Ping Su, Bang-Hung Yang, Ren-Shyan Liu, Cheng-Ta Li
• Journal: Journal of affective disorders (J Affect Disord) Vol. 235 Pg. 250-256 (08 01 2018) ISSN: 1573-2517 [Electronic] Netherlands
• PMID: 29660639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Receptors, Tumor Necrosis Factor, Type I
• Glutamic Acid

Topics

• Adult
• Brain (metabolism)
• Depressive Disorder, Major (blood)
• Depressive Disorder, Treatment-Resistant (blood)
• Female
• Glutamic Acid (metabolism)
• Gyrus Cinguli (physiopathology)
• Humans
• Male
• Middle Aged
• Positron-Emission Tomography
• Receptors, Tumor Necrosis Factor, Type I (blood)