Preschool is a sensitive period for the influence of maternal support on the trajectory of hippocampal development

Building on well-established animal data demonstrating the effects of early maternal support on hippocampal development and adaptive coping, a few longitudinal studies suggest that early caregiver support also impacts human hippocampal development. How caregiving contributes to human hippocampal developmental trajectories, whether there are sensitive periods for these effects, as well as whether related variation in hippocampal development predicts later childhood emotion functioning are of major public health importance. The current study investigated these questions in a longitudinal study of preschoolers assessed annually for behavioral and emotional development, including observed caregiver support. One hundred and twenty-seven children participated in three waves of magnetic resonance brain imaging through school age and early adolescence. Multilevel modeling of the effects of preschool and school-age maternal support on hippocampal volumes across the three waves was conducted. Hippocampal volume increased faster for those with higher levels of preschool maternal support. Subjects with support 1 SD above the mean had a 2.06 times greater increase in total hippocampus volume across the three scans than those with 1 SD below the mean (2.70% vs. 1.31%). No effect of school-age support was found. Individual slopes of hippocampus volume were significantly associated with emotion regulation at scan 3. The findings demonstrate a significant effect of early childhood maternal support on hippocampal volume growth across school age and early adolescence and suggest an early childhood sensitive period for these effects. They also show that this growth trajectory is associated with later emotion functioning.A large body of developmental data from studies of rodents has clearly established that the early experience of a highly nurturing caregiver has a powerful effect on hippocampal development in the rat pup, through an epigenetic mechanism (1–4). Building on these findings in animals, an increasing body of data in humans has emerged suggesting that early experiences of support, or conversely of abuse, neglect, or adversity, similarly impact human hippocampal development (5–7). The hippocampus, a region dense with glucocorticoid receptors, plays an integral role in the hypothalamic pituitary axis stress response (8, 9). Related to this role, reductions in hippocampal volume have been implicated in maladaptive stress reactivity and coping, as well as in affective psychopathology (10, 11). Therefore, a greater understanding of the environmental factors, particularly early caregiving experiences, that contribute to healthy hippocampal development in humans is of significant public health importance. Further, it is critical to examine whether variation in hippocampal development related to early caregiving predicts later childhood emotion functioning, as would be expected based on the animal data but not yet established in humans (12).Although retrospective studies establish a link between childhood trauma and abuse and decreases in hippocampal volume in adults, these findings are limited by the known bias and possible inaccuracy of retrospective accounts of early childhood experiences by adult reporters (13, 14). More recently, some prospective data have become available to inform this issue. Using one wave of scan data from the study sample presented here, we have previously reported a link between higher early childhood maternal support and larger hippocampal volumes measured at school age in nondepressed subjects (15). Another prospective study that followed a small sample of cocaine-exposed infants from birth through adolescence reported decreased hippocampal volumes in adolescents who experienced higher maternal nurturance at age 4 (16). Although this effect was opposite what would be expected from the animal literature, the use of a relatively small sample exposed to drugs in utero may represent a unique developmental trajectory. Alterations in patterns of connectivity between the medial prefrontal cortex and amygdala have been reported in children who experienced early maternal deprivation (17, 18). Notably, another unique prospective study of a small group of children exposed to chronically depressed and less nurturing mothers displayed increases in amygdala volumes but no changes in hippocampus when scanned at age 10 (19). These conflicting findings underscore the need for further investigation of these relationships in larger samples with broader early risk exposures. In addition, there is a need to examine brain outcomes across the trajectory of brain development using multiple scan waves longitudinally. It is possible that disparate findings may reflect the unique risk trajectories of the various study samples, small sample sizes, as well as the limitations of cross-sectional imaging outcomes. As such, the question of whether the effect of early caregiver support impacts hippocampal development across its growth trajectory is of key interest. The current study aimed to address this question using a longitudinal neuroimaging design across childhood to investigate whether there are effects of support on brain development from school age through early adolescence.Another key question that has been of interest in the study of the effects of caregiving quality on emotional, cognitive, and related brain development has been whether there are sensitive periods during which these environmental factors may have a particularly powerful effect on developmental outcomes. Such sensitive periods in development, when environmental exposures have a uniquely large and formative effect on neural structure and function, are well-established in visual and sensory-motor systems (20, 21). There has been some emerging evidence for sensitive periods in emotional development as well. This includes data from the Bucharest Early Intervention Project, where institutionalized children randomized to foster care before the age of 2 had superior cognitive and socioemotional outcomes to those randomized at later ages (22). Similarly, Rao et al. (16) report evidence for a sensitive period for the effects of maternal support (although in the opposite direction of that expected from animal studies), with childhood support at age 4 predicting adolescent brain outcomes whereas later childhood support at age 8 did not. If sensitive periods for the effects of supportive caregiving on brain development could be identified, it would have very important early intervention and prevention implications.To address these questions, we sought to investigate whether experiences of maternal support predicted the trajectory of hippocampal development through school age and early adolescence using a longitudinal neuroimaging study with three waves of structural imaging data. We also tested whether caregiver support during the preschool versus school-age periods had unique effects on hippocampal outcomes. Last, to better interpret the functional significance of any effects found on hippocampal growth trajectories, we examined whether these trajectories predicted emotion reactivity and/or regulation at late school age.