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The Role of the X-Linked EFHC2 Gene in Social Cognition in Neurotypical Males
Objectives: We investigated the influence of SNP rs7055196 on aspects of social cognition and related neural activity in neurotypical males to determine if this X-linked variation can help to account for the increased male vulnerability to impaired social cognition.
Methods: We compared neurotypical males possessing the A and G alleles at SNP rs7055196 on their facial fear recognition and theory of mind abilities, the face-selective N170 component (using event related potentials) and neural activity during a theory of mind task (using an fMRI paradigm).
Results: Males possessing the G allele showed poorer facial fear recognition accuracy compared to males possessing the A allele (P = 0.042, effect size = 0.214). Males possessing the G allele showed smaller N170 amplitudes in response to faces compared to males possessing the A allele (P = 0.028, effect size = 0.72). Males possessing the G allele were less accurate at inferring others’ mental states during the Reading the Mind in the Eyes task (a theory of mind task) (P = 0.045, effect size = 0.211), and showed reduced neural activity in the right superior temporal gyrus, left inferior parietal lobule and left cingulate gyrus during this task (P < 0.001 uncorrected) compared to males possessing the A allele.
Conclusions: The difference in fear recognition accuracy and N170 amplitude between the groups may be accounted for by males possessing the A allele using a more holistic/configural face processing mechanism than those possessing the G allele, as the N170 component is thought to be involved in holistic/configural face processing (i.e. processing faces as a whole). The group differences in theory of mind abilities and related brain activity may reflect higher empathising abilities in the males possessing the A allele, as activity in these regions has been linked to empathising. The effect sizes of these influences of SNP rs7055196 on social cognition were greater at the neural level compared to the behavioural level. Our results suggest an influence of SNP rs7055196 on social cognitive abilities in males. The location of this SNP on the X chromosome may contribute towards explaining the increased male vulnerability to impaired social cognition, helping to explain why males are more vulnerable to ASDs compared to females.