Testosterone-related cortical maturation across childhood and adolescence.
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ABSTRACT:
SUBMITTER: Nguyen TV
PROVIDER: S-EPMC3643718 | biostudies-literature | 2013 Jun
REPOSITORIES: biostudies-literature
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Project description:Interventions: Group 1: Patients with a malignant disease are initially reported to the German Childhood Cancer Registry (DKKR) by the pediatric oncology centers treating them. This generates a PatID (patient identifier) ??and a MaligID (malignant identifier). If there is a malignant endocrine tumor that is recorded in our registry, the DKKR sends a notification form with these two IDs to the MET registry center. The registry center then contacts the reporting pediatric oncology department and sends the patient information and declarations of consent.
The treating physicians initially check the existence of inclusion and exclusion criteria. Insofar as inclusion criteria are met but exclusion criteria are not present, there is detailed medical information and written information about the content, risks and benefits of the MET registry. If the patient and the legal guardian agree, the patient can be included in the MET registry. In some cases, pediatric oncology centers contact the MET Help Desk for clinical advice. Patient data in German-speaking countries is recorded via the GPOH platform MARVIN (XClinical) in so-called electronic Case Report Forms” (eCRFs).
The patient information and declarations of consent are then sent in this way.
Primary outcome(s): The primary objectives of the MET Registry include:
1. The prospective registration of all children and adolescents with an initial diagnosis of a malignant endocrine tumor between the ages of 0 and 18 years
2. The scientific evaluation with the aim of optimizing the therapy of affected patients
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: Prognosis
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Project description:ImportanceThe trajectory of cortical gray matter development in childhood has been characterized by early neurogenesis and volume increase, peaking at puberty followed by selective elimination and myelination, resulting in volume loss and thinning. This inverted U-shaped trajectory, as well as cortical thickness, has been associated with cognitive and emotional function. Synaptic pruning-based volume decline has been related to experience-dependent plasticity in animals. To date, there have been no data to inform whether and how childhood depression might be associated with this trajectory.ObjectiveTo examine the effects of early childhood depression, from the preschool age to the school age period, on cortical gray matter development measured across 3 waves of neuroimaging from late school age to early adolescence.Design, setting, and participantsData were collected in an academic research setting from September 22, 2003, to December 13, 2014, on 193 children aged 3 to 6 years from the St Louis, Missouri, metropolitan area who were observed for up to 11 years in a longitudinal behavioral and neuroimaging study of childhood depression. Multilevel modeling was applied to explore the association between the number of childhood depression symptoms and prior diagnosis of major depressive disorder and the trajectory of gray matter change across 3 scan waves. Data analysis was conducted from October 29, 2014, to September 28, 2015.Main outcomes and measuresVolume, thickness, and surface area of cortical gray matter measured using structural magnetic resonance imaging at 3 scan waves.ResultsOf the 193 children, 90 had a diagnosis of major depressive disorder; 116 children had 3 full waves of neuroimaging scans. Findings demonstrated marked alterations in cortical gray matter volume loss (slope estimate, -0.93 cm³; 95% CI, -1.75 to -0.10 cm³ per scan wave) and thinning (slope estimate, -0.0044 mm; 95% CI, -0.0077 to -0.0012 mm per scan wave) associated with experiencing an episode of major depressive disorder before the first magnetic resonance imaging scan. In contrast, no significant associations were found between development of gray matter and family history of depression or experiences of traumatic or stressful life events during this period.Conclusions and relevanceThis study demonstrates an association between early childhood depression and the trajectory of cortical gray matter development in late school age and early adolescence. These findings underscore the significance of early childhood depression on alterations in neural development.
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Project description:We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study (n = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single-nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between an SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex • SNP interaction, revealing a significant association only in females (b = -0.32, p = 1.8 × 10(-6)). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, p = 0.001) and femoral neck aBMD (b = 0.27, p = 3.0 × 10(-5)). In contrast, the sex • SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, p = 4.4 × 10(-4)) and distal radius aBMD (b = 0.27, p = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, p = 0.003). In total, significant sex • SNP interactions were found at 15 loci; pubertal stage • SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation.
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Project description:The cortex is organised into broadly hierarchical functional systems with distinct neuroanatomical characteristics reflected by macroscopic measures of cortical morphology. Diffusion-weighted magnetic resonance imaging allows the delineation of areal connectivity, changes to which reflect the ongoing maturation of white matter tracts. These developmental processes are intrinsically linked with timing coincident with the development of cognitive function. In this study, we use a data-driven multivariate approach, nonnegative matrix factorisation, to define cortical regions that co-vary together across a large paediatric cohort (n = 456) and are associated with specific subnetworks of cortical connectivity. We find that age between 3 and 21 years is associated with accelerated cortical thinning in frontoparietal regions, whereas relative thinning of primary motor and sensory regions is slower. Together, the subject-specific weights of the derived set of cortical components can be combined to predict chronological age. Structural connectivity networks reveal a relative increase in strength in connection within, as opposed to between hemispheres that vary in line with cortical changes. We confirm our findings in an independent sample.
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