Andy C. Belden

The Effects of Poverty on Childhood Brain Development: The Mediating Effect of Caregiving and Stressful Life Events

IMPORTANCE The study provides novel data to inform the mechanisms by which poverty negatively impacts childhood brain development. OBJECTIVE To investigate whether the income-to-needs ratio experienced in early childhood impacts brain development at school age and to explore the mediators of this effect. DESIGN, SETTING, AND PARTICIPANTS This study was conducted at an academic research unit at the Washington University School of Medicine in St Louis. 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 to 6 years prior to the time of a magnetic resonance imaging scan, during which they were evaluated on psychosocial, behavioral, and other developmental dimensions. Preschoolers included in the study were 3 to 6 years of age and were recruited from primary care and day care sites in the St Louis metropolitan area; they were annually assessed behaviorally for 5 to 10 years. Healthy preschoolers and those with clinical symptoms of depression participated in neuroimaging at school age/early adolescence. EXPOSURE Household poverty as measured by the income-to-needs ratio. MAIN OUTCOMES AND MEASURES Brain volumes of childrens white matter and cortical gray matter, as well as hippocampus and amygdala volumes, obtained using magnetic resonance imaging. 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 finding 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.

Preschool Depression: Homotypic Continuity and Course Over 24 Months

CONTEXT Childhood depression is a serious and relapsing psychiatric disorder. However, to date studies have focused mostly on children aged 6 years and older. Validation for depression in preschool children has been provided by 2 independent study samples. While several studies have demonstrated stability and poor outcomes of internalizing symptoms in preschoolers, there has not yet been longitudinal data available to inform the course of preschool depression and whether it shows homotypic continuity into early childhood. OBJECTIVE To examine the 24-month course of preschool depression and whether it showed homotypic vs heterotypic continuity or was a developmentally transient phenomenon. DESIGN Blindly rated, prospective, 24-month, longitudinal follow-up study. SETTING Community sites. Patients Three hundred six preschoolers aged 3 to 6 years recruited from community sites and oversampled for symptoms of depression. Main Outcome Measure Recurrence/stability of depression and predictors of course. RESULTS Preschoolers with depression at baseline had the highest likelihood of subsequent depression 12 and/or 24 months later compared with preschoolers with no baseline disorder and with those who had other psychiatric disorders. Preschoolers with depression at baseline were more likely to have later depression rather than other psychiatric disorders. Findings from a logistic regression analysis indicated that when controlling for demographic variables, risk factors, and comorbid disorders, depression during the preschool period and family history of affective disorders were the most robust and significant predictors of later depression. CONCLUSIONS Preschool depression, similar to childhood depression, is not a developmentally transient syndrome but rather shows chronicity and/or recurrence. Homotypic continuity of preschool MDD during a 24-month period was found. These results underscore the clinical and public health importance of identification of depression as early as preschool. Further follow-up of preschoolers with depression is warranted to inform the longitudinal course throughout childhood.

Maternal support in early childhood predicts larger hippocampal volumes at school age

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.

The clinical significance of preschool depression: Impairment in functioning and clinical markers of the disorder

OBJECTIVE While much is now known about depression during school age and adolescence, whether clinical depression can onset even earlier in development during the preschool period remains under explored. The earliest possible identification of depression may be important for the design of prevention and early developmental intervention programs. This study investigated functional impairment associated with depression, symptoms that served as the best markers of depression vs. other disorders, as well as depression severity between two depressed sub-groups and other diagnostic comparison groups. METHOD Three hundred and five preschoolers between the ages of 3.0 and 6.0 and their primary caregivers were recruited using a depression screening checklist distributed at community sites. The Preschool Age Psychiatric Assessment (PAPA) was used to derive psychiatric diagnoses in the study sample. Multivariate analyses of covariance were used to investigate the effects of depression on independent measures of functional impairment while controlling for the effects of co-morbidities. RESULTS Functional impairment specifically associated with depression was found in multiple domains and contexts, however depressed preschoolers were not developmentally delayed. The symptoms of guilt and extreme fatigue were found to be highly specific for preschool depression. A statistically significant hierarchy of depression severity was found between diagnostic comparison groups, in the expected direction with the highest in a melancholic subgroup. CONCLUSIONS Validation for preschool depression with associated functional impairment across contexts was found in preschool children. These findings replicate and extend earlier evidence for validity of MDD diagnosed in the preschool period and highlight the need for clinical attention. The finding that these depressed and impaired preschoolers were not yet developmentally delayed may have important public health significant significance as it suggests a possible window of opportunity for early intervention. Study findings were limited by reliance on parent and teacher informants and a cross-sectional view.

Trajectories of Preschool Disorders to Full DSM Depression at School Age and Early Adolescence: Continuity of Preschool Depression

OBJECTIVE Preschool-onset depression, a developmentally adapted form of depression arising between ages 3 and 6, has demonstrated numerous validated features, including characteristic alterations in stress reactivity and brain function. This syndrome is characterized by subthreshold DSM criteria for major depressive disorder, raising questions about its clinical significance. To clarify the utility and public health significance of the preschool-onset depression construct, the authors investigated diagnostic outcomes of preschool children at school age and in adolescence. METHOD In a longitudinal prospective study of preschool children, the authors assessed the likelihood of meeting full criteria for major depressive disorder at age 6 or later as a function of preschool depression, other preschool axis I disorders, maternal history of depression, nonsupportive parenting, and traumatic life events. RESULTS Preschool-onset depression emerged as a robust predictor of major depressive disorder in later childhood even after accounting for the effect of maternal history of depression and other risk factors. Preschool-onset conduct disorder also predicted major depression in later childhood, but this association was partially mediated by nonsupportive parenting, reducing by 21% the effect of preschool conduct disorder in predicting major depression. CONCLUSIONS Study findings provide evidence that this preschool depressive syndrome is a robust risk factor for developing full criteria for major depression in later childhood, over and above other established risk factors. The results suggest that attention to preschool depression and conduct disorder in addition to maternal history of depression and exposure to trauma may be important in identifying young children at highest risk for later major depression and applying early interventions.

Association between depression severity and amygdala reactivity during sad face viewing in depressed preschoolers: An fMRI study

BACKGROUND Previous research has indicated that symptom severity and amygdala reactivity during the viewing of facial expressions of emotion are related in depression. However, it remains unclear how early in development this can be detected. METHODS A sample of 11 depressed preschoolers (4.5±0.8; 6 males) participated in an fMRI experiment where they viewed facial expressions of emotion. A region of interest approach was used in order to examine the relationship between amygdala activation and depression severity. Additional whole-brain analyses were conducted and the results of these analyses were examined for potential relationships with depression severity. RESULTS Findings indicated that depressed preschoolers exhibited a significant positive relationship between depression severity and right amygdala activity when viewing facial expressions of negative affect. In addition, we found a significant positive relationship between degree of functional activation in the occipital cortex while viewing faces and level of depression severity. LIMITATIONS Additional research including a larger sample of depressed preschoolers, as well as a healthy comparison group, is needed to replicate the current findings and examine their specificity at this age. CONCLUSIONS This is the first study directly examining brain function in depressed preschoolers. The results suggest that, similar to older children and adults with depression, amygdala responsivity and degree of depression severity are related as early as age 3.

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

Significance Data from a longitudinal neuroimaging study beginning in the preschool period and including three brain scans through school age and early adolescence were used to investigate the effects of maternal support on the development of the hippocampus. Consistent with animal findings showing that early support enhances hippocampal development and later adaptive coping, findings demonstrated that early childhood maternal support predicted a steeper hippocampal growth trajectory. The data also suggested that early childhood was a sensitive period when the effects of support had a more powerful effect on hippocampal growth. The hippocampal growth trajectory was associated with better emotion regulation in early adolescence. Findings suggest that enhancing early childhood maternal support fosters healthy childhood brain development and emotion functioning. 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.

Subgenual cingulate connectivity in children with a history of preschool-depression

The subgenual anterior cingulate cortex (sgACC) presents altered functional connections with other regions of the brain in individuals with depression. However, the developmental nature of this phenomenon remains largely unexplored. Functional connections of the sgACC were examined in 36 school age children, 17 with a history of preschool onset major depressive disorder (PO-MDD). The sgACC exhibited increased connections with cognitive control regions in healthy children and increased connections with thalamic and parietal regions in the PO-MDD group. A significant correlation between dysregulated emotional behavior and connectivity of the sgACC and dorsal medial prefrontal cortex was also found. These findings demonstrate that atypical sgACC functional connections are evident as early as school age in children with a history of PO-MDD and suggest an association with a very early episode of depression.

The 2-week duration criterion and severity and course of early childhood depression: Implications for nosology

BACKGROUND Although validity for DSM-IV MDD symptom criteria in preschoolers has been demonstrated, whether the 2-week duration criterion is an appropriate threshold of clinical significance at this age remains unclear. The current study aimed to begin addressing this question. METHOD Three hundred and six preschoolers were recruited from community sites and followed longitudinally for 2 years. A subsample including healthy preschoolers (N=77) and those with MDD (N=74) were examined. The MDD group was further divided based upon meeting (DSM, N=24) or failing to meet (<DSM, N=50) the DSM-IV 2-week duration criterion. Groups were compared on parent and teacher report measures of symptom severity and functional impairment at baseline and 2-year follow-up. LIMITATIONS A larger sample of depressed preschoolers and refined measures of duration are needed to replicate the current study. RESULTS Preschoolers with MDD differed significantly from controls on the majority of measures examined regardless of duration status and time of assessment. Further, the DSM group significantly differed from the<DSM group at baseline on measures of MDD symptom severity and impairment. No differences in the risk of a MDD diagnosis at follow-up were found on the basis of duration group status. CONCLUSIONS DSM-IV duration criterion failed to capture all clinically affected preschoolers at baseline or confer greater predictive validity for a depression diagnosis 2 years later. Findings suggest that preschoolers meeting all DSM-IV MDD criteria except for episode duration exhibit a clinically significant form of depression and experience a 2-year MDD outcome similar to those meeting full criterion.

Effect of Hippocampal and Amygdala Connectivity on the Relationship Between Preschool Poverty and School-Age Depression

OBJECTIVE In this study, the authors tested the hypothesis that poverty experienced in early childhood, as measured by income-to-needs ratio, has an impact on functional brain connectivity at school age, which in turn mediates influences on child negative mood/depression. METHOD Participants were from a prospective longitudinal study of emotion development. Preschoolers 3-5 years of age were originally ascertained from primary care and day care sites in the St. Louis area and then underwent annual behavioral assessments for up to 12 years. Healthy preschoolers and those with a history of depression symptoms underwent neuroimaging at school age. Using functional MRI, the authors examined whole brain resting-state functional connectivity with the left and right hippocampus and amygdala. RESULTS Lower income-to-needs ratio at preschool age was associated with reduced connectivity between hippocampus and amygdala and a number of regions at school age, including the superior frontal cortex, lingual gyrus, posterior cingulate, and putamen. Lower income-to-needs ratio predicted greater negative mood/depression severity at school age, as did connectivity between the left hippocampus and the right superior frontal cortex and between the right amygdala and the right lingual gyrus. Connectivity mediated the relationship between income-to-needs ratio and negative mood/depression at the time of scanning. CONCLUSIONS These findings suggest that poverty in early childhood, as assessed by at least one measure, may influence the development of hippocampal and amygdala connectivity in a manner leading to negative mood symptoms during later childhood.