Oxytocin receptor gene rs53576 polymorphism modulates oxytocin–dopamine interaction and neuroticism traits—A SPECT study

Jul 9, 2014Psychoneuroendocrinology

Variation in the Oxytocin Receptor Gene Affects Oxytocin-Dopamine Interaction and Neuroticism Traits

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Abstract

Striatal dopamine transporter availability was significantly lower in individuals with the AG+GG genotype of the OXTR gene compared to those with the AA genotype (2.08±0.47 vs. 1.90±0.32, p=0.04).

A negative correlation was found between dopamine transporter availability and oxytocin levels in individuals with one or two copies of the G allele of the OXTR gene (r=-0.41, p=0.002).
The interaction between oxytocin levels and dopamine transporter availability was significantly correlated with neuroticism scores in the AA genotype group.
In the AA group with low oxytocin levels, dopamine transporter availability correlated with neuroticism scores (r=0.74, p=0.002).
The study suggests that the OXTR rs53576 genotype may influence the relationship between oxytocin and dopamine systems.
Carriers of specific rs53576 OXTR genotypes may exhibit increased biological sensitivity and stress reactivity.

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Brain oxytocin and dopamine systems interact to modulate social cognitive behavior. Whether the interactions are modulated by oxytocin receptor (OXTR) gene variations remains unclear. Considering the dopamine transporter (DAT) availability as an endophenotype and the degree of dopamine-mediated neuroticism as a phenotype of the OXTR genotypes, the current molecular imaging study used [(99m)Tc]TRODAT-1 single photon emission computed tomography (SPECT) to measure the striatal DAT availability and the 57-item Maudsley Personality Inventory to measure neuroticism personality traits in healthy individuals to investigate (A) the correlation between the rs53576 (G/A) of OXTR and the striatal DAT availability, (B) the correlation between the peripheral oxytocin level and striatal DAT availability among different OXTR rs53576 (G/A) genotypes, and (C) whether neuroticism traits could be modified by oxytocin in certain OXTR rs53576 genotypes. The results showed that the striatal DAT availability in the AG+GG group was significantly lower than that in the AA group (2.08±0.47 vs. 1.90±0.32, p=0.04). Only individuals with one or two copies of the G allele of rs53576 showed a negative correlation between DAT availability and oxytocin level (r=-0.41, p=0.002). Furthermore, the oxytocin×DAT interaction was significantly correlated with the MPI neuroticism score in the AA group. Further analyses showed that the DAT availability was correlated with the neuroticism score only in the AA group with a low oxytocin level (r=0.74, p=0.002). The results indicated that the OXTR rs53576 is connected with the striatal DAT availability in vivo and modulates the interactions between the oxytocinergic and dopaminergic systems. Carriers with a specific rs53576 OXTR genotype may present a greater biological sensitivity as well as stress reactivity in terms of environmental adaptation.

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Oxytocin receptor gene rs53576 polymorphism modulates oxytocin–dopamine interaction and neuroticism traits—A SPECT study

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