Research Article: Common oxytocin polymorphisms interact with maternal verbal aggression in early infancy impacting blood pressure at age 5-6: The ABCD study

Date Published: June 24, 2019

Publisher: Public Library of Science

Author(s): Laetitia J. C. A. Smarius, Thea G. A. Strieder, Theo A. H. Doreleijers, Tanja G. M. Vrijkotte, M. H. Zafarmand, Susanne R. de Rooij, Monica Uddin.


Early life stress has been shown to contribute to alterations in biobehavioral regulation. Genetic make-up, especially related to social sensitivity, might affect the child’s vulnerability to these alterations. This study examined whether maternal verbally aggressive behavior in early infancy interacts with oxytocin polymorphisms in changing resting cardiovascular outcomes at age 5–6. In the Amsterdam-Born-Children-and-their-Development-(ABCD)-study, a large prospective, observational, population-based birth cohort, maternal verbally aggressive behavior was assessed in the 13th postnatal week (range 11–25 weeks, SD 2 weeks) by a questionnaire (maternal self-report). Indicators of resting cardiac autonomic nervous system activity (sympathetic drive by pre-ejection period, parasympathetic drive by respiratory sinus arrhythmia), heart rate, and blood pressure were measured at age 5–6 years. Data on oxytocin receptor gene polymorphisms rs53576, rs2268498 and oxytocin polymorphisms rs2740210, rs4813627, were collected (N = 966 included). If the child was carrier of the rs53576 GG variant, exposure to maternal verbally aggressive behavior (10.6%) was associated with increased systolic blood pressure at age 5–6 (B = 4.9 mmHg,95% CI[2.2;7.7]). If the child was carrier of the rs2268498 TT/TC variant, exposure to maternal verbally aggressive behavior was associated with increased systolic blood pressure at age 5–6 (B = 3.0 mmHg,95%CI[1.0:5.0]). No significant interactions of maternal verbally aggressive behavior with oxytocin gene polymorphisms on heart rate or cardiac autonomic nervous system activity were found. In conclusion, oxytocin receptor gene polymorphisms may partly determine a child’s vulnerability to develop increased systolic blood pressure after being exposed to maternal verbally aggressive behavior in early infancy.

Partial Text

Infancy is a highly critical period for brain development. During the first months of life, essential brain structures are evolving and in basic structures synaptogenesis is accelerating [1]. Exposure to a single, but substantial, stressor during this early period might impact brain development and programming of the stress systems significantly. For instance, maternal report of interparental conflict has been positively associated with infants’ activation in brain regions related to emotion processing and stress regulation (anterior cingulate cortex, caudate nucleus (part of dorsal striatum), hypothalamus, and thalamus) in response to the sound of their mothers’ angry voice at age 6–12 months [2], implying programming effects. Of note, between 2–4 months of age, synaptogenesis in the striatum is most rapid and total gray matter volume of the striatum reaches adult size at about 4 months of age [1], emphasizing the potential impact of stress exposure in this period of life.

Our study shows novel evidence suggesting that OXTR gene variants might influence the vulnerability to develop increased SBP at age 5–6, after exposure to maternal verbally aggressive behavior in early infancy. Confirming our hypothesis, we found evidence for gene- environment interaction of OXTR polymorphisms rs53576 and rs2268498, both of which have previously been associated with facial emotion recognition [12,14]. Our findings of rs53576 are in line with a retrospective study on childhood maltreatment and adult emotional dysregulation, in which carriers of rs53576 GG were at risk for increased emotional dysregulation when exposed to three or more categories of childhood abuse. On the contrary, A-allele carriers were suggested to be resilient against the effects of severe childhood adversity [22]. In our study, exposed A-allele carriers also seemed resilient to increases in SBP. We found no significant gene-early environment interaction with respect to the OXT gene variants rs2740210 and rs4813627, and maternal verbally aggressive behavior in infancy in increasing SBP at age 5–6, although the non-significant interactions were in the same direction (S2A Fig and S2B Fig).




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