Variations in the TNF-α gene (TNF-α -308G→A) affect attention and action selection mechanisms in a double-dissociated fashion

Abstract

There is growing interest to understand the molecular basis of complex cognitive processes. While neurotransmitter systems have frequently been examined, other, for example neuroimmunological factors have attracted much less interest. Recent evidence suggests that the A allele of the tumor necrosis factor alpha (TNF-α) 308G→A single nucleotide polymorphism (SNP; rs1800629) enhances cognitive functions. However, it is also known that TNF-α exerts divergent, region-specific effects on neuronal functioning. Thus the finding that the A allele is associated with enhanced cognitive performance may be due to regionally specific effects of TNF-α. In this study, associations between the TNF-α -308G→A single nucleotide polymorphism (rs1800629) and cognitive function in an event-related potential (ERP) study in healthy participants (n = 96) are investigated. We focus on subprocesses of stimulus-response compatibility that are known to be mediated by different brain systems. The results show a dissociative effect of the TNF- 308G→A SNP on ERPs reflecting attentional (N1) versus conflict and action selection processes [N2 and early-lateralized readiness potential (e-LRP)] between the AA/AG and the GG genotypes. Compared with the GG genotype group, attentional processes (N1) were enhanced in the combined AA/AG genotype group, while conflict processing functions (N2) and the selection of actions (LRP) were reduced. The results refine the picture of the effects of the TNF-α -308G→A SNP on cognitive functions and emphasize the known divergent effects of TNF-α on brain functions.