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Attachment is a biological evolutionary system contributing to infant survival. When primary caregivers/parents are sensitive and responsive to their infants’ needs, infants develop a sense of security. Secure infant attachment has been linked to healthy brain and organ-system development. Belsky and colleagues proposed the term differential susceptibility to describe context-dependent associations between genetic variations and behavioral outcomes as a function of parenting environments. Variations in the Cannabinoid Receptor Gene 1 (CNR1) are associated with memory, mood, and reward and connote differential susceptibility to more and less optimal parental caregiving quality in predicting children’s behavioral problems.   Aim  To determine if parental caregiving quality interacts with children’s expression-based polygenic risk score (ePRS) for the CNR1 gene networks in the prefrontal cortex, striatum, and hippocampus in predicting the probability of attachment security and disorganized attachment.    Design  Prospective correlational methods examined maternal-infant pairs ( n  = 142) from which infants provided DNA samples at 3 months. Parental caregiving quality was assessed via the Child Adult Relationship Experiment (CARE)-index at 6 months, and attachment security via the Strange Situation Procedure at a mean age of 22 months. The CNR1 ePRSs include genes co-expressed with the CNR1 genes in the prefrontal cortex, striatum, or hippocampus, and were calculated using the effect size of the association between the individual single nucleotide polymorphisms from those genes and region-specific gene expression (GTEx). Logistic regression was employed (alpha < 0.05, two-tailed) to examine the main and interaction effects between parental caregiving quality and ePRSs in predicting attachment patterns. Interpretation of results was aided by analyses that distinguished between differential susceptibility and diathesis-stress.    Results  Significant interactions were observed between (1) maternal sensitivity and ePRS in the striatum in predicting attachment security, (2) maternal unresponsiveness with the ePRS in the hippocampus in predicting disorganization, and (3) maternal controlling with the ePRS in the hippocampus in predicting disorganization.    Conclusion  These findings offer support for genetic differential susceptibility to the quality of maternal sensitivity in the context of the ePRS in the striatum. However, the significant interactions between hippocampal ePRS and maternal unresponsiveness and controlling in predicting the probability of disorganization were more suggestive of the diathesis-stress model.

frontiers in neuroscience

Associations Among Parental Caregiving Quality, Cannabinoid Receptor 1 Expression-Based Polygenic Scores, and Infant-Parent Attachment: Evidence for Differential Genetic Susceptibility?