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15 things your doctor doesn't know about your child : questions answered about developmental delays
Board Certified Pediatric Chiropractor Dr. Amber Brooks offers parents information on understanding how developmental delays can be caught early and even treated when found. She outlines potential problems and symptoms to help parents determine the root cause of the delay, using real life examples and the medical basis and philosophies involved with their treatments. Spanning multiple diagnoses and all of their respective symptoms, Dr. Brooks, DC, CACCP combines medical and alternative models to care for a child individually, examining the whole child rather than particular symptoms, to provide an individualized and comprehensive approach to pediatric wellness. -- Adapted from publisher description.
Book
Becoming a Member of the Speech Community: Learning Socio‐Phonetic Variation in Child Language
This chapter contains sections titled:
Introduction
What is sociolinguistic variation in child language?
Child‐directed speech
Acquisition of dialectal norms
Conclusions
References
Book Chapter
Functional impact of global rare copy number variation in autism spectrum disorders
The genetics of autism
The autism spectrum disorders (ASDs) are a group of conditions typically characterized by repetitive behaviour, severely restricted interests and difficulties with social interactions and communication. ASDs are highly heritable, yet the underlying genetic determinants remain largely unknown. A genome-wide analysis reveals that people with ASDs carry a higher load of rare copy-number variants — segments of DNA for which the copy number differs between individual genomes — which are either inherited or arise
de novo
. The results implicate several novel genes as ASD candidates and point to the importance of cellular proliferation, projection and motility as well as specific signalling pathways in this disorder.
The autistic spectrum disorders (ASDs) are highly heritable, yet the underlying genetic determinants remain largely unknown. Here, a genome-wide analysis of rare copy number variants (CNVs) has been carried out, revealing that ASD sufferers carry a higher load of rare, genic CNVs than do controls. Many of these CNVs are
de novo
and inherited. The results implicate several novel genes in ASDs, and point to the importance of cellular proliferation, projection and motility, as well as specific signalling pathways, in these disorders.
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours
1
. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability
2
. Although ASDs are known to be highly heritable (∼90%)
3
, the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold,
P
= 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold,
P
= 3.4 × 10
-4
). Among the CNVs there were numerous
de novo
and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as
SHANK2, SYNGAP1
,
DLGAP2
and the X-linked
DDX53–PTCHD1
locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Journal Article
Systematic identification of genetic influences on methylation across the human life course
Background
The influence of genetic variation on complex diseases is potentially mediated through a range of highly dynamic epigenetic processes exhibiting temporal variation during development and later life. Here we present a catalogue of the genetic influences on DNA methylation (methylation quantitative trait loci (mQTL)) at five different life stages in human blood: children at birth, childhood, adolescence and their mothers during pregnancy and middle age.
Results
We show that genetic effects on methylation are highly stable across the life course and that developmental change in the genetic contribution to variation in methylation occurs primarily through increases in environmental or stochastic effects. Though we map a large proportion of the
cis
-acting genetic variation, a much larger component of genetic effects influencing methylation are acting in
trans
. However, only 7 % of discovered mQTL are
trans
-effects, suggesting that the
trans
component is highly polygenic. Finally, we estimate the contribution of mQTL to variation in complex traits and infer that methylation may have a causal role consistent with an infinitesimal model in which many methylation sites each have a small influence, amounting to a large overall contribution.
Conclusions
DNA methylation contains a significant heritable component that remains consistent across the lifespan. Our results suggest that the genetic component of methylation may have a causal role in complex traits. The database of mQTL presented here provide a rich resource for those interested in investigating the role of methylation in disease.
Journal Article
Prolonged myelination in human neocortical evolution
Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.
Journal Article
The Differential Impacts of Early Physical and Sexual Abuse and Internalizing Problems on Daytime Cortisol Rhythm in School-Aged Children
The impact of early physical and sexual abuse (EPA/SA) occurring in the first 5 years of life was investigated in relation to depressive and internalizing symptomatology and diurnal cortisol regulation. In a summer camp context, school-aged maltreated (n = 265) and nonmaltreated (n = 288) children provided morning and late afternoon saliva samples on 5 consecutive days. Child self-report and adult observer reports of child internalizing and depressive symptoms were obtained. Children experiencing EPA/SA and high depressive or internalizing symptoms uniquely exhibited an attenuated diurnal decrease in cortisol, indicative of neuroendocrine dysregulation. These results were specific to EPA/SA rather than later onset physical or sexual abuse or early occurring neglect or emotional maltreatment.
Journal Article
Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study
Objective To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.Design Population based nested case-control study. Setting Stockholm County, Sweden, 2001-07.Participants 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years.Main outcome measure A diagnosis of autism spectrum disorder, with or without intellectual disability.Exposures Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.Results A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.Conclusions In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.
Journal Article
Inter-individual variability in structural brain development from late childhood to young adulthood
A fundamental task in neuroscience is to characterize the brain's developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently been identified, we have yet to quantify and understand individual differences in structural brain development. The present study examined inter-individual variability and sex differences in changes in brain structure, as assessed by anatomical MRI, across ages 8.0–26.0 years in 269 participants (149 females) with three time points of data (807 scans), drawn from three longitudinal datasets collected in the Netherlands, Norway, and USA. We further investigated the relationship between overall brain size and developmental changes, as well as how females and males differed in change variability across development. There was considerable inter-individual variability in the magnitude of changes observed for all examined brain measures. The majority of individuals demonstrated decreases in total gray matter volume, cortex volume, mean cortical thickness, and white matter surface area in mid-adolescence, with more variability present during the transition into adolescence and the transition into early adulthood. While most individuals demonstrated increases in white matter volume in early adolescence, this shifted to a majority demonstrating stability starting in mid-to-late adolescence. We observed sex differences in these patterns, and also an association between the size of an individual's brain structure and the overall rate of change for the structure. The present study provides new insight as to the amount of individual variance in changes in structural morphometrics from late childhood to early adulthood in order to obtain a more nuanced picture of brain development. The observed individual- and sex-differences in brain changes also highlight the importance of further studying individual variation in developmental patterns in healthy, at-risk, and clinical populations.
Journal Article
Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome
The 22q11.2 deletion syndrome (22q11DS) is associated with a 20–25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.
Polygenic risk scores are nearing a level of differentiation required for their clinical utility in risk prediction in populations with high-risk rare pathogenic genetic variants.
Journal Article
Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders
Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27 de novo events in 16 genes, 59% of which are predicted to truncate proteins or disrupt splicing. We estimate that recurrent disruptive mutations in six genes—CHD8, DYRK1A, GRIN2B, TBR1, PTEN, and TBL1XR1—may contribute to 1% of sporadic ASDs. Our data support associations between specific genes and reciprocal subphenotypes (CHD8-macrocephaly and DYRK1A-microcephaly) and replicate the importance of a β-catenin—chromatin-remodeling network to ASD etiology.
Journal Article