Neurobiological correlates of externalizing and prosocial behavior in school-age children

This thesis describes a series of studies on the neurobiological correlates of externalizing and prosocial behavior in six-to ten-year old children. Chapter 1 provides an outline and describes the background and aims of our work. The studies described in this thesis are embedded in the Generation R study, a prospective cohort from fetal life onwards in Rotterdam, the Netherlands. We describe both structural (chapter 2, 3, and 6) and functional neuroimaging studies (chapter 4 and 5) on the association between externalizing and prosocial behavior and the brain, and examine behavior both from a trait-like perspective (chapter 2 and 3) a

Pubertal development mediates the association between family environment and brain structure and function in childhood

Psychosocial acceleration theory suggests that pubertal maturation is accelerated in response to adversity. In addition, suboptimal caregiving accelerates development of the amygdala-medial prefrontal cortex circuit. These findings may be related. Here, we assess whether associations between family environment and measures of the amygdala-medial prefrontal cortex circuit are mediated by pubertal development in more than 2000 9- and 10-year-old children from the Adolescent Brain Cognitive Development Study (http://dx.doi.org/10.15154/1412097). Using structural equation modeling, demographic, child-reported, and parent-reported data on family dynamics were compiled into a higher level family environment latent variable. Magnetic resonance imaging preprocessing and compilations were performed by the Adolescent Brain Cognitive Development Study's data analysis core. Anterior cingulate cortex (ACC) thickness, area, white matter fractional anisotropy, amygdala volume, and cingulo-opercular network-amygdala resting-state functional connectivity were assessed. For ACC cortical thickness and ACC fractional anisotropy, significant indirect effects indicated that a stressful family environment relates to more advanced pubertal stage and more mature brain structure. For cingulo-opercular network-amygdala functional connectivity, results indicated a trend in the expected direction. For ACC area, evidence for quadratic mediation by pubertal stage was found. Sex-stratified analyses suggest stronger results for girls. Despite small effect sizes, structural measures of circuits important for emotional behavior are associated with family environment and show initial evidence of accelerated pubertal development

The longitudinal association between externalizing behavior and frontoamygdalar resting‐state functional connectivity in late adolescence and young adulthood

Background: Externalizing behavior has been attributed, in part, to decreased frontolimbic control over amygdala activation. However, little is known about developmental trajectories of frontoamygdalar functional connectivity and its relation to externalizing behavior. The present study addresses this gap by examining longitudinal associations between adolescent and adult externalizing behavior and amygdala–anterior cingulate cortex (ACC) and amygdala– orbitofrontal cortex (OFC) resting-state functional connectivity in a sample of 111 typically developing participants aged 11–23 at baseline. Methods: Participants completed two-to-four data waves spaced approximately two years apart, resulting in a total of 309 data points. At each data wave, externalizing behavior was measured using the Externalizing Behavior Broadband Scale from the Achenbach Youth/Adult Self-Report questionnaire. Resting-state fMRI preprocessing was performed using FS

The Association of Gender, Age, and Intelligence With Neuropsychological Functioning in Young Typically Developing Children: The Generation R Study

2016 Copyrigh

Brain morphology of childhood aggressive behavior: A multi-informant study in school-age children

Objective: Few studies have focused on the neuroanatomy of aggressive behavior in children younger than 10 years. Here, we explored the neuroanatomical correlates of aggression in a population-based sample of 6- to 9-year-old children using a multiple-informant approach. Methods: Magnetic resonance (MR) scans were acquired from 566 children from the Generation R study who participated in the Berkeley Puppet Interview and whose parents had completed the Child Behavior Checklist. Linear regression analyses were used to examine associations between aggression and amygdala and hippocampal volume. We performed surface-based analyses to study the association between aggression and cortical thickness, surface area, and gyrification. Results: Aggressive behavior was associated with smaller amygdala (p <.05) but not hippocampal volume. Aggression was associated with a thinner cortex in the left precentral cortex (p <.01) and in a cluster including the right inferior parietal, supramarginal, and postcentral cortex (p <.001). Gender moderated the association between aggression and cortical thickness in the right medial posterior cortex (p =.001) and the right prefrontal cortex (p <.001). Aggression was associated with decreased gyrification in a large cluster including the right precentral, postcentral, frontal, and parietal cortex (p =.01). Moreover, aggression was associated with decreased gyrification in the right occipital and parietal cortex (p =.02). Conclusion: We found novel evidence that childhood aggressive behavior is related to decreased amygdala volume, decreased sensorimotor cortical thickness, and decreased global right hemisphere gyrification. Aggression is related to cortical thickness in regions associated with the default mode network, with negative associations in boys and positive associations in girls

Novel mutations in the VKORC1 gene of wild rats and mice – a response to 50 years of selection pressure by warfarin?

<p>Abstract</p> <p>Background</p> <p>Coumarin derivatives have been in world-wide use for rodent pest control for more than 50 years. Due to their retarded action as inhibitors of blood coagulation by repression of the vitamin K reductase (VKOR) activity, they are the rodenticides of choice against several species. Resistance to these compounds has been reported for rodent populations from many countries around the world and poses a considerable problem for efficacy of pest control.</p> <p>Results</p> <p>In the present study, we have sequenced the <it>VKORC1 </it>genes of more than 250 rats and mice trapped in anticoagulant-exposed areas from four continents, and identified 18 novel and five published missense mutations, as well as eight neutral sequence variants, in a total of 178 animals. Mutagenesis in <it>VKORC1 </it>cDNA constructs and their recombinant expression revealed that these mutations reduced VKOR activities as compared to the wild-type protein. However, the <it>in vitro </it>enzyme assay used was not suited to convincingly demonstrate the warfarin resistance of all mutant proteins</p> <p>Conclusion</p> <p>Our results corroborate the <it>VKORC1 </it>gene as the main target for spontaneous mutations conferring warfarin resistance. The mechanism(s) of how mutations in the <it>VKORC1 </it>gene mediate insensitivity to coumarins <it>in vivo </it>has still to be elucidated.</p

The Road Less Traveled: Regulation of Leukocyte Migration Across Vascular and Lymphatic Endothelium by Galectins

Leukocyte entry from the blood into inflamed tissues, exit into the lymphatics, and migration to regional lymph nodes are all crucial processes for mounting an effective adaptive immune response. Leukocytes must cross two endothelial cell layers, the vascular and the lymphatic endothelial cell layers, during the journey from the blood to the lymph node. The proteins and cellular interactions which regulate leukocyte migration across the vascular endothelium are well studied; however, little is known about the factors that regulate leukocyte migration across the lymphatic endothelium. Here, we will summarize evidence for a role for galectins, a family of carbohydrate-binding proteins, in regulating leukocyte migration across the vascular endothelium and propose that galectins are also involved in leukocyte migration across the lymphatic endothelium

Exploring the transition into fatherhood: behavioral, hormonal, and neural underpinnings of responses to infant crying

In the present hypothesis generating study, behavioral and neural responses to infant crying, as well as paternal hormone levels, were measured in both the prenatal and early postnatal period. Using a longitudinal design, we investigated parental sensitivity, handgrip force, and neural activation in response to infant crying sounds, in addition to testosterone baseline levels, in 25 first-time fathers. We describe the extent to which these aspects of paternal care are related across the perinatal period. The current exploratory study adds to the understudied field of early paternal care by making recommendations, and proposing hypotheses for future studies