Functions of CNKSR2 and Its Association with Neurodevelopmental Disorders.
Ontology highlight
ABSTRACT:
SUBMITTER: Ito H
PROVIDER: S-EPMC8774548 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) - prevalent and often highly comorbid neurodevelopmental disorders - others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and children with ASD and ADHD. We employed a latent profile analysis using indicators of EF (e.g., working memory, inhibition, and flexibility) in a mixed group of 8-13 year-olds including TD children (n?=?128), children with ASD without ADHD (n?=?30), children with ADHD (n?=?93), and children with comorbid ASD and ADHD (n?=?66). Three EF classes emerged: "above average," "average," and "impaired." EF classes did not reproduce diagnostic categories, suggesting that differences in EF abilities are present within the ASD and ADHD groups. Further, greater EF dysfunction predicted more severe socioemotional problems, such as anxiety/depression. These results highlight the heterogeneity of current diagnostic groups and identify an "impaired" EF group, consisting of children with both ASD and ADHD, which could specifically be targeted for EF intervention.
| S-EPMC5101520 | biostudies-literature
Project description:ImportanceGiven the critical role that iron plays in neurodevelopment, an association between prenatal iron deficiency and later risk of neurodevelopmental disorders, such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), is plausible.ObjectiveTo test the a priori hypothesis that anemia diagnosed in mothers during pregnancy is associated with an increased risk of ASD, ADHD, and ID in offspring and that the magnitude of the risk varies with regard to the timing of anemia in pregnancy.Design, setting, and participantsThis cohort study used health and population register data from the Stockholm Youth Cohort to evaluate 532?232 nonadoptive children born from January 1, 1987, to December 31, 2010, in Sweden, with follow-up in health registers until December 31, 2016. Data analysis was performed from January 15, 2018, to June 20, 2018.ExposuresRegistered diagnoses of anemia during pregnancy. Gestational timing of the first recorded anemia diagnosis (?30 weeks or >30 weeks) was considered to assess potential critical windows of development.Main outcomes and measuresRegistered diagnoses of ASD, ADHD, or ID or co-occurring combinations of these disorders.ResultsThe cohort included 532 232 individuals (272 884 [51.3%] male) between 6 and 29 years of age at the end of follow-up (mean [SD] age, 17.6 [7.1] years) and their 299 768 mothers. The prevalence of ASD, ADHD, and ID was higher among children born to mothers diagnosed with anemia within the first 30 weeks of pregnancy (4.9% ASD, 9.3% ADHD, and 3.1% ID) compared with mothers with anemia diagnosed later in pregnancy (3.8% ASD, 7.2% ADHD, and 1.1% ID) or mothers not diagnosed with anemia (3.5% ASD, 7.1% ADHD, and 1.3% ID). Anemia diagnosed during the first 30 weeks of pregnancy but not later was associated with increased risk of diagnosis of ASD (odds ratio [OR], 1.44; 95% CI, 1.13-1.84), ADHD (OR, 1.37; 95% CI, 1.14-1.64), and ID (OR, 2.20; 95% CI, 1.61-3.01) in offspring in models that included socioeconomic, maternal, and pregnancy-related factors. Early anemia diagnosis was similarly associated with risk of ASD (OR, 2.25; 95% CI, 1.24-4.11) and ID (OR, 2.59; 95% CI, 1.08-6.22) in a matched sibling comparison. Considering mutually exclusive diagnostic groups, we observed the strongest association between anemia and ID without co-occurring ASD (OR, 2.72; 95% CI, 1.84-4.01). Associations of these disorders with anemia diagnosed later in pregnancy were greatly diminished.Conclusions and relevanceIn contrast to maternal anemia diagnosed toward the end of pregnancy, anemia diagnosed earlier in pregnancy was associated with increased risk of the development of ASD, ADHD, and particularly ID in offspring. Given that iron deficiency and anemia are common among women of childbearing age, our findings emphasize the importance of early screening for iron status and nutritional counseling in antenatal care.
| S-EPMC6751782 | biostudies-literature
Project description:The present study examines the comorbidity between specific learning disorders (SLD) and attention deficit and hyperactivity disorder (ADHD) by comparing the neuropsychological profiles of children with and without this comorbidity. Ninety-seven schoolchildren from 8 to 14 years old were tested: a clinical sample of 49 children with ADHD (n = 18), SLD (n = 18) or SLD in comorbidity with ADHD (n = 13), and 48 typically-developing (TD) children matched for age and intelligence. Participants were administered tasks and questionnaires to confirm their initial diagnosis, and a battery of executive function (EF) tasks testing inhibition, shifting, and verbal and visuospatial updating. Using one-way ANOVAs, our results showed that all children in the clinical samples exhibited impairments on EF measures (inhibition and shifting tasks) when compared with TD children. A more specific pattern only emerged for the updating tasks. Only children with SLD had significant impairment in verbal updating, whereas children with ADHD, and those with SLD in comorbidity with ADHD, had the worst performance in visuospatial updating. The clinical and educational implications of these findings are discussed.
| S-EPMC7958764 | biostudies-literature
Project description:In this review we examine the current understanding of how genetic deficits associated with neurodevelopmental disorders may impact synapse assembly. We then go on to discuss how the critical periods for these genetic deficits will shape the nature of future clinical interventions.
| S-EPMC4262893 | biostudies-other
Project description:ImportancePreeclampsia during pregnancy has been linked to an increased risk of cerebral palsy in offspring. Less is known about the role of preeclampsia in other neurodevelopmental disorders.ObjectiveTo determine the association between preeclampsia and a range of adverse neurodevelopmental outcomes in offspring after excluding preterm births.Design, setting, and participantsThis prospective, population-based cohort study included singleton children born at term from January 1, 1991, through December 31, 2009, and followed up through December 31, 2014 (to 5 years of age), using Norway's Medical Birth Registry and linked to other demographic, social, and health information by Statistics Norway. Data were analyzed from May 30, 2018, to November 17, 2019.ExposuresMaternal preeclampsia.Main outcomes and measuresAssociations between preeclampsia in term pregnancies and cerebral palsy, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), epilepsy, intellectual disability, and vision or hearing loss using multivariable logistic regression.ResultsThe cohort consisted of 980 560 children born at term (48.8% female and 51.2% male; mean [SD] gestational age, 39.8 [1.4] weeks) with a mean (SD) follow-up of 14.0 (5.6) years. Among these children, 28 068 (2.9%) were exposed to preeclampsia. Exposed children were at increased risk of ADHD (adjusted odds ratio [OR], 1.18; 95% CI, 1.05-1.33), ASD (adjusted OR, 1.29; 95% CI, 1.08-1.54), epilepsy (adjusted OR, 1.50; 95% CI, 1.16-1.93), and intellectual disability (adjusted OR, 1.50; 95% CI, 1.13-1.97); there was also an apparent association between preeclampsia exposure and cerebral palsy (adjusted OR, 1.30; 95% CI, 0.94-1.80).Conclusions and relevancePreeclampsia is a well-established threat to the mother. Other than the hazards associated with preterm delivery, the risks to offspring from preeclampsia are usually regarded as less important. This study's findings suggest that preeclampsia at term may have lasting effects on neurodevelopment of the child.
| S-EPMC7113825 | biostudies-literature
Project description:ImportanceHypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.ObjectiveTo investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.Design, setting, and participantsThis Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.ExposuresDiagnoses of HDP, which were provided by the Medical Birth Register.Main outcomes and measuresDiagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.ResultsThe study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, -0.10; 95% CI, -0.13 to -0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, -0.09 to 0.08).Conclusions and relevanceThe study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.
| S-EPMC7985818 | biostudies-literature
Project description:BackgroundMaternal diabetes has been associated with a risk of neurodevelopmental disorders (NDDs) in offspring, though the common co-occurrence of autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID) is rarely considered, nor is the potential for confounding by shared familial factors (e.g. genetics).MethodsThis population-based cohort study used data from Psychiatry Sweden, a linkage of Swedish national registers, to follow 2 369 680 individuals born from 1987 to 2010. We used population-averaged logit models to examine the association between exposure to maternal type 1 diabetes mellitus (T1DM), pre-gestational type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM), and odds of NDDs in offspring. Subgroup analysis was then performed to investigate the timings of GDM diagnosis during pregnancy and its effect on the odds of NDDs in offspring. We compared these results to models considering paternal lifetime T1DM and T2DM as exposures.ResultsOverall, 45 678 individuals (1.93%) were diagnosed with ASD, 20 823 (0.88%) with ID and 102 018 (4.31%) with ADHD. All types of maternal diabetes were associated with odds of NDDs, with T2DM most strongly associated with any diagnosis of ASD (odds ratioadjusted 1.37, 95% confidence interval 1.03-1.84), ID (2.09, 1.53-2.87) and ADHD (1.43, 1.16-1.77). Considering common co-morbid groups, the associations were strongest between maternal diabetes and diagnostic combinations that included ID. Paternal T1DM and T2DM diagnoses were also associated with offspring NDDs, but these associations were weaker than those with maternal diabetes. Diagnosis of GDM between 27 and 30 weeks of gestation was generally associated with the greatest risk of NDDs in offspring, with the strongest associations for outcomes that included ID.ConclusionThe association of maternal diabetes with NDDs in offspring varies depending on the co-morbid presentation of the NDDs, with the greatest odds associated with outcomes that included ID. Results of paternal-comparison studies suggest that the above associations are likely to be partly confounded by shared familial factors, such as genetic liability.
| S-EPMC8128461 | biostudies-literature
Project description:With increasing numbers of children being diagnosed with neurodevelopmental disorders (NDDs) attention has been drawn to these children's physical health. We aimed to identify the prevalence of defined physical problems (epilepsy, migraine, asthma, cancer, diabetes, psoriasis, lactose intolerance, celiac disease, diarrhea, constipation, daytime enuresis, encopresis) in a nationwide population of 9- and 12-year-old twins subdivided into those with and without indications of NDDs. Parents of 28,058 twins participated in a well-validated telephone interview regarding their children's mental health and answered questions about their physical problems. The results indicate a high rate of physical problems in children with NDDs, particularly in those with indications of the presence of combinations of several NDDs.
| S-EPMC6331488 | biostudies-other
Project description:Many neurological disorders affect men and women differently regarding prevalence, progression, and severity. It is clear that many of these disorders may originate from defective signaling during fetal or perinatal brain development, which may affect males and females differently. Such sex-specific differences may originate from chromosomal or sex-hormone specific effects. This short review will focus on the estrogen receptor beta (ERβ) signaling during perinatal brain development and put it in the context of sex-specific differences in neurodevelopmental disorders. We will discuss ERβ's recent discovery in directing DNA de-methylation to specific sites, of which one such site may bear consequences for the susceptibility to the neurological reading disorder dyslexia. We will also discuss how dysregulations in sex-hormone signaling, like those evoked by endocrine disruptive chemicals, may affect this and other neurodevelopmental disorders in a sex-specific manner through ERβ.
| S-EPMC5366823 | biostudies-literature
Project description:Neurodevelopmental disorders (NDDs) are caused by mutations in diverse genes involved in different cellular functions, although there can be crosstalk, or convergence, between molecular pathways affected by different NDDs. To assess molecular convergence, we generated human neural progenitor cell models of 9q34 deletion syndrome, caused by haploinsufficiency of EHMT1, and 18q21 deletion syndrome, caused by haploinsufficiency of TCF4. Using next-generation RNA sequencing, methylation sequencing, chromatin immunoprecipitation sequencing, and whole-genome miRNA analysis, we identified several levels of convergence. We found mRNA and miRNA expression patterns that were more characteristic of differentiating cells than of proliferating cells, and we identified CpG clusters that had similar methylation states in both models of reduced gene dosage. There was significant overlap of gene targets of TCF4 and EHMT1, whereby 8.3% of TCF4 gene targets and 4.2% of EHMT1 gene targets were identical. These data suggest that 18q21 and 9q34 deletion syndromes show significant molecular convergence but distinct expression and methylation profiles. Common intersection points might highlight the most salient features of disease and provide avenues for similar treatments for NDDs caused by different genetic mutations.
| S-EPMC4225591 | biostudies-literature