Serum Levels of Tumor Necrosis Factor-alpha and Loudness Dependence of Auditory Evoked Potentials at Pretreatment and Posttreatment in Patients with Major Depressive Disorder

Abstract

Background: Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are associated with the pathophysiology of major depressive disorder (MDD). Several studies have reported that increased TNF-alpha might be associated with tryptophan depletion, which eventually could result in MDD. However, other studies revealed that TNF-alpha increased serotonin firing in raphe. Therefore, whether TNF-alpha increases or decreases serotonin activity remains unclear. Here, we aimed to determine the relationship between serum TNF-alpha level and central serotonergic activity using the loudness dependence of auditory evoked potentials (LDAEP) and standardized low-resolution brain electromagnetic tomography (sLORETA), as well as to evaluate the effects of antidepressants on TNF-alpha levels. Methods: LDAEP, serum TNF-alpha level, and depression severity were measured in 64 MDD outpatients pre and post 3 months of treatment. Results: Pretreatment TNF-alpha levels were negatively correlated with the pretreatment N1 sLORETA-LDAEP, P2 sLORETA-LDAEP, and N1/P2 sLORETA-LDAEP (p < 0.05). In multiple regression analysis for N1/P2 sLORETA-LDAEP, lower N1/P2 sLORETA-LDAEP was significantly related to higher TNF-alpha (CE = -0.047, p = 0.017) when all subjects were dichotomized based on the median TNF-alpha level (7.16 pg/mL) into pretreatment low- and high-TNF-alpha groups. In addition, the pretreatment Beck Depression Inventory, P2 LDAEP, and N1/P2 sLORETA-LDAEP were greater in the high-TNF-alpha groups than in the low-TNF-alpha groups (p < 0.05). Moreover, the posttreatment TNF-alpha level was significantly decreased compared to the pretreatment TNF-alpha level (z = -2.581, p = 0.01). However, the posttreatment TNF-alpha levels were not associated with posttreatment LDAEP. Conclusions: Higher TNF-alpha level is associated with decreased LDAEP, which could indicate compensatory elevation of central serotonin activity in outpatients with MDD, although this effect disappeared and TNF-alpha level was reduced after three months of antidepressant treatment.