Respiratory sinus arrhythmia in the fourth decade of life depends on birth weight and the DRD4 gene: Implications for understanding the development of emotion regulation

INTRODUCTION: The long allele of the DRD4 gene can confer different behavioral and emotional phenotypes depending upon environmental exposure, although the physiological changes underlying these phenotypes are not fully known. We sought to extend this work by assessing the interaction of the DRD4 gene and exposure to perinatal adversity (indexed by extremely low birth weight [ELBW]) on resting respiratory sinus arrhythmia (RSA), a neurophysiological measure of emotion regulation, in adulthood. METHODS: We examined the interaction between the DRD4 gene and perinatal adversity on RSA at age 30-35 in a longitudinal cohort of ELBW survivors (n = 49) and NBW controls (n = 63). Buccal DNA samples were genotyped for short and long carriers of the exon III DRD4 VNTR gene. Resting RSA was assessed by electrocardiogram. RESULTS: We report an interaction between birth weight status and DRD4 gene (F = 9.42, p = 0.003) in predicting RSA, such that DRD4 long carriers had the highest and lowest resting RSA depending on whether they were born NBW or ELBW, respectively. DRD4 short carriers were less sensitive to birth weight. Additionally, reduced RSA was correlated with a history of major depressive disorder, suggesting it was a reliable index of emotion dysregulation. DISCUSSION: These results suggest that the perinatal environment influences autonomic nervous system functioning in individuals with genotypes that confer additional sensitivity. Whether the long-term autonomic outcomes of this environmental sensitivity are beneficial or detrimental appears to depend on the quality of the early life environment, and may influence the development of emotion regulatory and psychiatric problems in adulthood.