Der Zusammenhang von Bindungssicherheit und einer Oxytocinrezeptor-Genvariation mit neuralen Korrelaten sozialer Kognition und Hirnmorphometrie

Human socio-cognitive, -emotional and neural brain development is not only shaped by genes, but also by early caregiving experiences⁠. A framework for the understanding of the socio-cognitive and -emotional development as a consequence of early caregiving experiences and biological dispositions is offered by attachment theory⁠. Individual attachment styles evolve over time into a moderately stable personality trait that affect social cognition, social behavior and coping with stressful life events (like e.g. affective loss experiences)⁠. The attachment system is physiologically connected to the oxytocin system. The oxytocin system plays a significant role in human social behavior and cognition and its development is shaped by early parent-infant interactions. In human genetic approaches the polymorphism of the oxytocin receptor (OXTR) gene rs53576 has been linked to varying sensitivity to social stimuli⁠. Rs53576 also interacted with early social experiences to modulate socioemotional personality traits. Questions: This research project addressed the question how neural correlates of mentalizing and brain morphometry are associated a) with childhood attachment security taking the OXTR gene polymorphism rs53576 into account and b) with adult attachment style. Methods: In a sample of healthy students the neural correlates of mentalizing were investigated by functional magnetic resonance imaging (MRI) during a socially interactive theory-of-mind task (ToM, Prisoner's Dilemma Game, n=164). Brain morphometry was assessed as brain gray matter volume applying structural MRI and voxel-based morphometry (VBM, n=196). Questionnaires were administered to assess childhood attachment security (CAS, Hazan-Shaver Scale), adult attachment style (Relationship Scales Questionnaire, subscales „anxiety“ (ANX) and „avoidance“ (AV)), alexithymia (Toronto Alexithymia Scale 20) and the number of affective loss experiences (AL, List of Threatening Experiences Questionnaire, VBM: n=192). The OXTR gene variant rs53576 (G/A) was assessed by genotyping of DNA from blood samples (ToM: n=163, VBM: n=195). Results: Rs53576 and CAS significantly interacted (i.e. GxE-interaction) on ANX, alexithymia, brain morphometry and function: Structural GxE-interaction effects were observed in a bilateral fronto-parietal and left temporal network (including hippo­campus and amygdala). Functional GxE-interaction effects were found in a right frontal and bilateral parieto-temporo-occipital ToM-related neural network. GG-homozygotes compared to A-allele carriers were more susceptible to CAS with regard to brain morphometry, ANX and alexithymia. Some of the observed GxE-interaction effects were sexually dimorphic. Structural and functional GxE-interaction effects partially overlapped in several brain regions. Exploratory regression analyses showed that both structural and functional GxE-interaction effects were associated with each other and with ANX and alexithymia. Additionally GG-homozygotes compared to A-allele carriers displayed significantly higher gray matter volume in temporal poles and hippocampus. The adult attachment styles AV and ANX significantly differed in their association with ToM-related neural activations (in bilateral inferior frontal gyri (IFG), right middle cingulate cortex and amygdala among others) and brain gray matter volume in the pars opercularis of the left IFG. Discussion: Interaction effects of CAS and rs53576 on brain gray matter volume and ToM-related neural activations were particularly observed in brain areas that are involved in social cognition like ToM and the mirror neuron system. Structural GxE-interaction effects and genetic main effects were found in brain regions that are related to memory functions. Genetic effects on memory and/or epigenetic mechanisms could play a role in the observed GxE-interaction effects on brain structure, brain function and socioemotional personality traits. AV and ANX significantly differed in their association with ToM-associated neural activations and with the volume of brain regions which play a role in emotion regulation. The results of this research are a further step in understanding the biological under­pinnings of attachment. They offer new insights how the neurobiological foundations of social cognition might develop in an interplay of attachment security and genetic variations.