These findings validate the existence, long-episode duration, and chronicity of child mania. Differences from the natural history of adult bipolar disorder are discussed.

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

Background Preschool-onset depression, a developmentally adapted form of depression arising between the ages of 3–6, has demonstrated numerous features of validity including characteristic alterations in stress reactivity and brain function. Notably, this validated syndrome with multiple clinical markers is characterized by sub-threshold DSM Major Depressive Disorder criteria, raising questions about its clinical significance. To clarify the utility and public health significance of the preschool-onset depression construct, diagnostic outcomes of this group at school age and adolescence were investigated. Methods We investigated the likelihood of meeting full DSM Major Depressive Disorder criteria in later childhood (i.e., ≥ age 6) as a function of preschool depression, other preschool Axis I disorders, maternal depression, parenting non-support and traumatic life events in a longitudinal prospective study of preschool children. Results Preschool-onset depression emerged as a robust predictor of DSM-5 Major Depressive Disorder in later childhood even after accounting for the effect of maternal depression and other risk factors. Preschool-onset conduct disorder also predicted DSM-5 Major Depressive Disorder in later childhood, but this association was partially mediated by maternal non-support, reducing the effect of preschool conduct disorder in predicting DSM depression by 21%. Discussion Study findings provide evidence that this preschool depressive syndrome is a robust risk factor for meeting full DSM criteria for Major Depressive Disorder in later childhood over and above other established risk factors. Preschool conduct disorder also predicted Major Depressive Disorder but was mediated by maternal non-support. Findings suggest that attention to preschool depression and conduct disorder in addition to maternal depression and exposure to trauma should now become an important factor for identification of young children at highest risk for later MDD who should be targeted for early interventions.

This finding in child bipolar disorder is consistent with data for adults with bipolar disorder that show preferential transmission of the Val66 allele.

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.maternal support | hippocampus | sensitive period | preschool | emotions