The Effects of HPA Axis Genetic Variation and Early Life Stress on Cortisol Levels in Preschool Age Children and on Amygdala and Hippocampus Volumes, Reactivity, and Connectivity at School Age

Internalizing psychopathology has been linked to increased cortisol reactivity and alterations in limbic brain structure and function, yet the mechanisms underlying these alterations are unclear. One key hypothesis is that stress plays a major causal role in these mechanisms. Animal studies find that chronic stress or glucocorticoid administration lead to alterations in hippocampal and amygdala structure and function. Relatedly, life stress is a major risk factors for depression while candidate gene studies have related variation in hypothalamic-pituitary-adrenal (HPA) axis genes to increased prevalence and severity of depression. The present work tested the hypothesis that genetic profile scores combining variance across 10 single nucleotide polymorphisms from four HPA axis genes (CRHR1, NR3C2, NR3C1, FKBP5) and early life stress would predict increases in stress cortisol levels in preschool-age children as well as alterations in hippocampal and amygdala volumes, reactivity, and resting state functional connectivity in these same children at school age. The current results indicate that (1) childhood stress exposure and genetic profile scores both predict stress cortisol, (2) these factors interact to predict volumetric alterations, partially mediated by cortisol, (3) life stress predicts left amygdala reactivity while genetic profile scores interact with sex and pubertal status to predict amygdala and hippocampus reactivity to negative emotional stimuli, and (4) these factors and their interaction predict weakened amygdala functional connectivity with subcortical and prefrontal regions. Overall, these findings suggest a key role for stress exposure, genetic risk, and cortisol in contributing to individual differences in amygdala and hippocampus structure and function typically associated with internalizing pathology

Construyendo, explorando y jugando con triángulos

En el presente trabajo, nuestro objetivo es dar a conocer una experiencia de clase que nos permitió “dar vida” a las construcciones de triángulos en el aula. Esta secuencia didáctica está basada en las dificultades clásicas que siempre ha tenido la Geometría, como por ejemplo: la falta de dinamismo, la dificultad en la construcción de las figuras, entre otras. Por esta razón, es que destacamos, que el uso del GeoGebra permite abordar a la Geometría, a través de la experimentación y la exploración, desarrollando habilidades de visualización que, en otras oportunidades, han quedado relegadas al “ingenio” del docente frente a un pizarrón estático y, muchas veces, poco práctico para trabajar. Las construcciones realizadas son precisas y permiten, en forma sencilla, realizar complejizaciones y/o modificaciones posteriores, con solo “mover” los objetos libres

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

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

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

Ventral Striatum and the Evaluation of Memory Retrieval Strategies

Abstract ■ Adaptive memory retrieval requires mechanisms of cognitive control that facilitate the recovery of goal-relevant information. Frontoparietal systems are known to support control of memory retrieval. However, the mechanisms by which the brain acquires, evaluates, and adapts retrieval strategies remain unknown. Here, we provide evidence that ventral striatal activation tracks the success of a retrieval strategy and correlates with subsequent reliance on that strategy. Human participants were scanned with fMRI while performing a lexical decision task. A rule was provided that indicated the likely semantic category of a target word given the category of a preceding prime. Reliance on the rule improved decision-making, as estimated within a drift diffusion framework. Ventral striatal activation tracked the benefit that relying on the rule had on decision-making. Moreover, activation in ventral striatum correlated with a participantʼs subsequent reliance on the rule. Taken together, these results support a role for ventral striatum in learning and evaluating declarative retrieval strategies.

Revising the BIS/BAS Scale to study development: Measurement invariance and normative effects of age and sex from childhood through adulthood.

Carver and White\u27s (1994) Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales have been useful tools for studying individual differences in reward-punishment sensitivity; however, their factor structure and invariance across development have not been well tested. In the current study, we examined the factor structure of the BIS/BAS Scales across 5 age groups: 6- to 10-year-old children (N = 229), 11- to 13-year-old early adolescents (N = 311), 14- to 16-year-old late adolescents (N = 353), 18- to 22-year-old young adults (N = 844), and 30- to 45-year-old adults (N = 471). Given poor fit of the standard 4-factor model (BIS, Reward Responsivity, Drive, Fun Seeking) in the literature, we conducted exploratory factor analyses in half of the participants and identified problematic items across age groups. The 4-factor model showed poor fit in our sample, whereas removing the BAS Fun Seeking subscale and problematic items from the remaining subscales improved fit in confirmatory factor analyses conducted with the second half of the participants. The revised model showed strict invariance across age groups and by sex, indicating consistent factor structure, item loadings, thresholds, and unique or residual variances. Additionally, in our cross-sectional data, we observed nonlinear relations between age and subscale scores, where scores tended to be higher in young adulthood than in childhood and later adulthood. Furthermore, sex differences emerged across development; adolescent and adult females had higher BIS scores than males in this age range, whereas sex differences were not observed in childhood. These differences may help us to understand the rise in internalizing psychopathology in adolescence, particularly in females. Future developmental studies are warranted to examine the impact of rewording problematic items

Efficacy and mechanisms underlying a gamified attention bias modification training in anxious youth: protocol for a randomized controlled trial

Background Attention bias modification training (ABMT) and cognitive behavioral therapy (CBT) likely target different aspects of aberrant threat responses in anxiety disorders and may be combined to maximize therapeutic benefit. However, studies investigating the effect of ABMT in the context of CBT have yielded mixed results. Here, we propose an enhanced ABMT to target the attentional bias towards threat, in addition to classic CBT for anxiety disorders in youth. This enhanced ABMT integrates the modified dot-probe task used in previous studies, where a target is always presented at the previous location of the neutral and not the simultaneously presented threatening stimulus, with a visual search, where the targets are always presented distally of threatening distractors. These two training elements (modified dot-probe and visual search) are embedded in an engaging game to foster motivation and adherence. Our goal is to determine the efficacy of the enhanced ABMT in the context of CBT. Further, we aim to replicate two previous findings: (a) aberrant amygdala connectivity being the neurobiological correlate of the attentional bias towards threat at baseline; and (b) amygdala connectivity being a mediator of the ABMT effect. We will also explore moderators of treatment response (age, sex, depressive symptoms and irritability) on a behavioral and neuronal level. Methods One hundred and twenty youth (8–17 years old) with a primary anxiety disorder diagnosis all receive CBT and are randomized to nine weeks of either active or control ABMT and symptom improvement will be compared between the two study arms. We will also recruit 60 healthy comparison youth, who along with eligible anxious youth, will be assessed with the dot-probe task during fMRI (anxious youth: before and after training; healthy volunteers: second measurement twelve weeks after initial assessment). Discussion The present study will contribute to the literature by (1) potentially replicating that aberrant amygdala connectivity mediates the attentional bias towards threat in anxious youth; (2) determining the efficacy of enhanced ABMT; and (3) advancing our understanding of the mechanisms underlying ABMT. Trial registration Clinicaltrials.gov: NCT03283930 Trial registration date: September 14th 2017. The trial registration took place retrospectively. Data acquisition started February 1st 2017

Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety

Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology