Double dissociated effects of the functional TNF-α -308G/A polymorphism on processes of cognitive control

Neuroimmunological factors may modulate brain functions and are important to understand the molecular basis of cognition. The tumor necrosis factor alpha (TNF-α) is known to induce neurodegenerative changes in the basal ganglia, but the cognitive effects of these changes are not understood. Since the basal ganglia are neurobiologically heterogeneous, different cognitive functions mediated by basal ganglia-prefrontal loops (response inhibition and error processing) may not necessarily be uniformly affected. Response inhibition and error processing functions were examined using event-related potentials (ERPs) and subjects (N=71) were genotyped for the functional TNF-α -308G→A polymorphism. We show a double-dissociated effect of the functional TNF-α -308G→A polymorphism on response inhibition and error processing. While response inhibition functions were more effective in the AA/AG genotype group, error monitoring functions are adversely affected in this genotype group. In the GG genotype group, the pattern of results was vice versa. The results refine the view of the effects of TNF-α on cognitive functions.