Cognition-immune interactions between executive function and working memory, tumour necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNFR1 and sTNFR2) in bipolar disorder

June 2, 2021

Authors: Robson Zazula, Seetal Dodd, Olivia M Dean, Michael Berk, Chiara C Bortolasci, Waldiceu A Verri Jr, Heber O Vargas, Sandra O V Nunes

Journal: The World Journal of Biological Psychiatry

DOI: 10.1080/15622975.2021.1925152

Year Published: 2021


This study examined cognition-immune interactions, specifically executive function, working memory, peripheral levels of tumour necrosis factor-alpha (TNF-α), and soluble tumour necrosis factor receptors-1 and -2 (sTNFR1 and 2) levels in patients in comparison with controls.


Thirty-one BD participants and twenty-seven controls participated in the study. The neurocognitive assessment was performed through three of CogState Research BatteryTM tasks for executive function and working memory. Plasma levels of TNF-α, sTNFR1, and sTNFR2 were measured after overnight fasting. Sociodemographic data and symptom severity of depression and mania were assessed.


BD presented a significantly worse performance in the working memory task (p = 0.005) and higher levels of TNF-α (p = 0.043) in comparison to controls. A trend level of significance was found for sTNFR1 between groups (p = 0.082). Among BD participants, there were significant correlations between sTNFR2 and neurocognitive tasks (Groton Maze Learning Task: ρ = 0.54, p = 0.002; Set-Shifting Task: ρ = 0.37, p = 0.042; and the Two-Back Task: ρ=-0.49, p = 0.005), and between sTNFR1 and mania, depression and anxiety symptoms (respectively ρ = 0.37, p = 0.038; ρ=-0.38, p = 0.037; and ρ = 0.42, p = 0.002).


TNF-α and its receptors might be an important variable in cognitive impairment in BD. Future studies might focus on the development of anti-inflammatory therapeutic targets for cognitive dysfunction in BD.

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