Association of timing of adverse childhood experiences and caregiver support with regionally specific brain development in adolescents

Importance: Few data are available to inform the associations and timing of the associations between adversity, caregiver support, and brain outcomes. Consideration of timing has important public health implications to inform more precise prevention strategies. Objective: To evaluate the timing and regional specificity of the association between adverse childhood experiences (ACEs) and caregiver support to structural development of limbic and striatal brain regions in middle childhood and adolescence. Design, Setting, and Participants: This 15-year developmental, neuroimaging cohort study included 211 children and their caregivers screened from day care centers and preschools in the St Louis, Missouri, metropolitan area during the preschool period, with an additional 4 waves of neuroimaging at school age through adolescence from November 14, 2007, to August 29, 2017. The cohort was oversampled for preschoolers with elevated symptoms of depression using a brief screener. Data analysis was performed from March 19, 2019, to July 26, 2019. Main Outcomes and Measures: Volumes in adolescence and developmental trajectories of volumes of the amygdala, hippocampus, caudate, subgenual cingulate, and insula during 4 waves of scanning; ACEs and observed caregiver support at preschool and school age; and volumes of amygdala, hippocampus, insula, and subgenual cingulate during 4 waves of scanning. Results: A total of 211 children (107 [50.7%] male) completed at least 1 scan. At preschool (mean [SD] age, 5.5 [0.8] years), ACE data were available for 164 children (84 [51.2%] male) and maternal support data for 155 children; at school age (mean [SD], 8.3 [1.2] years), ACE data were available for 172 children and maternal support data for 146 children. Unique patterns of the association between ACEs and support were found, with an association between the interaction of preschool ACEs and school-age support and the development of the hippocampus (t = -2.27; P = .02) and amygdala (t = -2.12; P = .04). A buffering hypothesis was not confirmed because high caregiver support was more strongly associated with the development of these regions only in the context of low ACEs. In contrast, preschool ACEs (t = -2.30; P = .02) and support (t = 2.59; P = .01) had independent associations with the development of the caudate. Conclusions and Relevance: The findings suggest that there are unique regional associations of support and adversity with key brain structures important for emotional regulation. Results may inform the timing and potential targets of preventive action for the range of poor developmental outcomes

Neural activation associated with the cognitive emotion regulation of sadness in healthy children

AbstractWhen used effectively, cognitive reappraisal of distressing events is a highly adaptive cognitive emotion regulation (CER) strategy, with impairments in cognitive reappraisal associated with greater risk for psychopathology. Despite extensive literature examining the neural correlates of cognitive reappraisal in healthy and psychiatrically ill adults, there is a dearth of data to inform the neural bases of CER in children, a key gap in the literature necessary to map the developmental trajectory of cognitive reappraisal. In this fMRI study, psychiatrically healthy schoolchildren were instructed to use cognitive reappraisal to modulate their emotional reactions and responses of negative affect after viewing sad photos. Consistent with the adult literature, when actively engaged in reappraisal compared to passively viewing sad photos, children showed increased activation in the vlPFC, dlPFC, and dmPFC as well as in parietal and temporal lobe regions. When children used cognitive reappraisal to minimize their experience of negative affect after viewing sad stimuli they exhibited dampened amygdala responses. Results are discussed in relation to the importance of identifying and characterizing neural processes underlying adaptive CER strategies in typically developing children in order to understand how these systems go awry and relate to the risk and occurrence of affective disorders

Evidence for dissociable cognitive and neural pathways from poverty versus maltreatment to deficits in emotion regulation

Poverty and threat exposure (TE) predict deficits in emotion regulation (ER). Effective cognitive ER (i.e., reappraisal) may be supported by: (1) cognitive processes implicated in generating and implementing cognitive reappraisal, supported by activation in brain regions involved in cognitive control (e.g., frontal, insular, and parietal cortices) and (2) emotion processing and reactivity, involving identification, encoding, and maintenance of emotional states and related variation in brain activity of regions involved in emotional reactivity (i.e., amygdala). Poverty is associated with deficits in cognitive control, and TE with alterations in emotion processing and reactivity. Our goal was to identify dissociable emotional and cognitive pathways to ER deficits from poverty and TE. Measures of cognitive ability, emotional processing and reactivity, ER, and neural activity during a sadness ER task, were examined from a prospective longitudinal study of youth at risk for depression (n = 139). Both cognitive ability and left anterior insula extending into the frontal operculum activity during a sadness reappraisal task mediated the relationship between poverty and ER. Emotion processing/reactivity didn\u27t mediate the relationship of TE to ER. Findings support a cognitive pathway from poverty to ER deficits. They also underscore the importance of dissociating mechanisms contributing to ER impairments from adverse early childhood experiences

Brain-behavior relationships in the experience and regulation of negative emotion in healthy children: Implications for risk for childhood depression

Structural and functional alterations in a variety of brain regions have been associated with depression and risk for depression across the life span. A majority of these regions are associated with emotion reactivity and/or regulation. However, it is generally unclear what mechanistic role these alterations play in the etiology of depression. A first step toward understanding this is to characterize the relationships between variation in brain structure/function and individual differences in depression severity and related processes, particularly emotion regulation. To this end, the current study examines how brain structure and function predict concurrent and longitudinal measures of depression symptomology and emotion regulation skills in psychiatrically healthy school-age children (N = 60). Specifically, we found that smaller hippocampus volumes and greater responses to sad faces in emotion reactivity regions predict increased depressive symptoms at the time of scan, whereas larger amygdala volumes, smaller insula volumes, and greater responses in emotion reactivity regions predict decreased emotion regulation skills. In addition, larger insula volumes predict improvements in emotion regulation skills even after accounting for emotion regulation at the time of scan. Understanding brain–behavior relationships in psychiatrically healthy samples, especially early in development, will help inform normative developmental trajectories and neural alterations in depression and other affective pathology

Preschool sleep and depression interact to predict gray matter volume trajectories across late childhood to adolescence

There is a close relationship between sleep and depression, and certain maladaptive outcomes of sleep problems may only be apparent in individuals with heightened levels of depression. In a sample enriched for preschool depression, we examined how sleep and depression in early childhood interact to predict later trajectories of gray matter volume. Participants (N = 161) were recruited and assessed during preschool (ages 3-6 years) and were later assessed with five waves of structural brain imaging, spanning from late childhood to adolescence. Sleep and depression were assessed using a semi-structured parent interview when the children were preschool-aged, and total gray matter volume was calculated at each scan wave. Although sleep disturbances alone did not predict gray matter volume/trajectories, preschool sleep and depression symptoms interacted to predict later total gray matter volume and the trajectory of decline in total gray matter volume. Sleep disturbances in the form of longer sleep onset latencies, increased irregularity in the child\u27s sleep schedule, and higher levels of daytime sleepiness in early childhood were all found to interact with early childhood depression severity to predict later trajectories of cortical gray matter volume. Findings provide evidence of the interactive effects of preschool sleep and depression symptoms on later neurodevelopment

Functional connectivity of the amygdala and subgenual cingulate during cognitive reappraisal of emotions in children with MDD history is associated with rumination

AbstractMajor Depressive Disorder (MDD) is characterized by poor emotion regulation. Rumination, a maladaptive strategy for dealing with negative emotions, is common in MDD, and is associated with impaired inhibition and cognitive inflexibility that may contribute to impaired emotion regulation abilities. However, it is unclear whether rumination is differently associated with emotion regulation in individuals with MDD history (MDD-ever) and healthy individuals. In this study, children (8–15 years old) performed a cognitive reappraisal task in which they attempted to decrease their emotional response to sad images during fMRI scanning. Functional connectivity (FC) between both the amygdala and subgenual anterior cingulate (sACC) increased with cortical control regions during reappraisal as rumination increased in MDD-ever, while connectivity between those regions decreased during reappraisal as rumination increased in healthy controls. As the role of cortical control regions is to down-regulate activity of emotion processing regions during reappraisal, this suggests that rumination in MDD-ever, but not controls, is associated with inefficient regulation. This finding suggests that rumination may be particularly associated with poor emotion regulation in MDD-ever, and may also indicate qualitative group differences in whether rumination is maladaptive. These differences in rumination may provide important insight into depressive risk and potential avenues for treatment

Excitability and irritability in preschoolers predicts later psychopathology: The importance of positive and negative emotion dysregulation

Emotion dysregulation is a risk factor for the development of a variety of psychopathologic outcomes. In children, irritability, or dysregulated negative affect, has been the primary focus, as it predicts later negative outcomes even in very young children. However, dysregulation of positive emotion is increasingly recognized as a contributor to psychopathology. Here we used an exploratory factor analysis and defined four factors of emotion dysregulation: irritability, excitability, sadness, and anhedonia, in the preschool-age psychiatric assessment collected in a sample of 302 children ages 3-5 years enriched for early onset depression. The irritability and excitability factor scores defined in preschoolers predicted later diagnosis of mood and externalizing disorders when controlling for other factor scores, social adversity, maternal history of mood disorders, and externalizing diagnoses at baseline. The preschool excitability factor score predicted emotion lability in late childhood and early adolescence when controlling for other factor scores, social adversity, and maternal history. Both excitability and irritability factor scores in preschoolers predicted global functioning into the teen years and early adolescence, respectively. These findings underscore the importance of positive, as well as negative, affect dysregulation as early as the preschool years in predicting later psychopathology, which deserves both further study and clinical consideration