Importance The study provides novel data to inform the mechanisms by which poverty negatively impacts childhood brain development. Objective To investigate whether income to needs ratio experienced in early childhood impacts brain development at school age and to explore the mediators of this effect. Design Data from a prospective longitudinal study of emotion development in preschool children who participated in neuroimaging at school age were used to investigate the effects of poverty on brain development. Children were assessed annually for 3-6 years prior to the time of a MRI scan during which they were evaluated on psychosocial, behavioral and other developmental dimensions. Setting An academic research unit at the Washington University School of Medicine. Participants Preschoolers 3- 6 years of age were ascertained from primary care and day care sites in the St. Louis metropolitan area and annually assessed behaviorally for 5-10 years. Healthy preschoolers and those with clinical symptoms of depression participated in neuroimaging at school age/early adolescence. Main Outcome Measure(s) The main outcomes of interest were brain volumes of children's white matter and cortical gray matter as well as hippocampus and amygdala obtained using MRI. Mediators of interest were caregiver support/hostility measured observationally during the preschool period and stressful life events measured prospectively. Results Poverty was associated with smaller white and cortical gray matter and hippocampal and amygdala volumes. The effects of poverty on hippocampal volume were mediated by caregiving support/hostility on the left and right as well as stressful life events on the left. Conclusions and Relevance The findings that exposure to poverty in early childhood materially impacts brain development at school age further underscores the importance of attention to the well established deleterious effects of poverty on child development. Findings that these effects on the hippocampus are mediated by caregiving and stressful life events suggest that attempts to enhance early caregiving should be a focused public health target for prevention and early intervention. Findings substantiate the behavioral literature on the negative effects of poverty on child development and provide new data confirming that effects extend to brain development. Mechanisms for these effects on the hippocampus are suggested to inform intervention.

Early maternal support has been shown to promote specific gene expression, neurogenesis, adaptive stress responses, and larger hippocampal volumes in developing animals. In humans, a relationship between psychosocial factors in early childhood and later amygdala volumes based on prospective data has been demonstrated, providing a key link between early experience and brain development. Although much retrospective data suggests a link between early psychosocial factors and hippocampal volumes in humans, to date there has been no prospective data to inform this potentially important public health issue. In a longitudinal study of depressed and healthy preschool children who underwent neuroimaging at school age, we investigated whether early maternal support predicted later hippocampal volumes. Maternal support observed in early childhood was strongly predictive of hippocampal volume measured at school age. The positive effect of maternal support on hippocampal volumes was greater in nondepressed children. These findings provide prospective evidence in humans of the positive effect of early supportive parenting on healthy hippocampal development, a brain region key to memory and stress modulation.depression | parental support | nurturance | neurodevelopment

Patients with major depression may have structural abnormalities of the hippocampus that can be detected by analysis of hippocampal shape but not volume. A specific defect in the subiculum could have widespread effects throughout neurocircuits that appear to be abnormal in depression.

Findings suggest that although there were no significant differences in amygdala volumes between groups, familial factors influence amygdala volumes. Discrepancies between studies measuring amygdala volume in MDD may be due to differences in amygdala boundary definitions.

Although hippocampal atrophy and altered functional brain responses to emotional stimuli have been found in major depressive disorder (MDD), the relationship between the two is not yet well understood. The present study focused on children with and without a history of preschool onset MDD (PO-MDD) and directly examined the relations between hippocampal volume and functional brain activation to affect-eliciting stimuli. Children completed annual diagnostic assessments starting at preschool. When children were school-aged, high-resolution structural MRI and task-related functional MRI data were acquired from N = 64 nonmedicated children. During fMRI, subjects were shown emotional faces. Results from the total sample indicated that smaller bilateral hippocampal volumes were associated with greater cortico-limbic (e.g., amygdala, hippocampus, dorso-lateral prefrontal cortex) activation to sad or negative faces versus neutral faces. Left hippocampal volume was negatively associated with the cortico-limbic activation in both the PO-MDD and healthy children. Right hippocampal volume was negatively correlated with amygdala responses in the PO-MDD group, but not in the healthy comparison group. These findings suggest that there may be important interrelationships between reduced hippocampal volume and hyperactivation of brain responses in children, both those with and those without a history of PO-MDD.