Neurobiological pathways to childhood psychopathology : Population-based studies of cognition and behavior

In the past few decades, considerable advances have been made in understanding childhood psychopathology. This progress is the result of four primary developments in the field. First, both in the research and in the clinical framework, psychopathology has been conceptualized across a spectrum of severity of symptoms and impairment. Second, psychopathology has been studied in the context of young children’s real life parallel to referral settings. Third, studying child psychopathology in large-scale prospective epidemiological studies offers new insight into the etiology of child psychiatric disorders. And fourth, enormous progress has been made in understanding the nature of psychopathology and its biological underpinnings

Gestational Age at Birth and Risk of Developmental Delay: The Upstate KIDS Study

Objective—To model the association between gestational age at birth and early child development through 3 years of age. Study Design—Development of 5868 children in Upstate KIDS (New York State; 2008–2014) was assessed at 7 time-points using the Ages and Stages Questionnaire (ASQ). The ASQ was implemented using gestational age corrected dates of birth at 4, 8, 12, 18, 24, 30, and 36 months. Whether children were eligible for developmental services from the Early Intervention Program (EIP) was determined through linkage. Gestational age was based on vital records. Statistical models adjusted for covariates including sociodemographic factors, maternal smoking and plurality. Results——Compared to gestational age of 39 weeks, adjusted odds ratios (aOR) and 95% confidence intervals of failing the ASQ for children delivered at \u3c 32, 32–34, 35–36, 37, 38, and 40 weeks gestational age were: 5.32 (3.42, 8.28), 2.43 (1.60, 3.69), 1.38 (1.00, 1.90), 1.37 (0.98, 1.90), 1.29 (0.99, 1.67), 0.73 (0.55, 0.96), and 0.51 (0.32, 0.82). Similar risks of being eligible for EIP services were observed (aOR: 4.19, 2.10, 1.29, 1.20, 1.01, 1.00 (ref), 0.92, 0.78, respectively for \u3c 32, 32–34, 37, 38, 39 (ref), 40, 41 weeks). Conclusion—Gestational age was inversely associated with developmental delays for all gestational ages. Evidence from our study is potentially informative for low-risk deliveries at 39 weeks but it is notable that deliveries at 40 weeks exhibited further lower risk

Maternal urinary iodine concentration in pregnancy and children's cognition: Results from a population-based birth cohort in an iodine-sufficient area

OBJECTIVE: Reports from populations with an insufficient iodine intake suggest that children of mothers with mild iodine deficiency during pregnancy are at risk for cognitive impairments. However, it is unknown whether, even in iodine-sufficient areas, low levels of iodine intake occur that influence cognitive development in the offspring. This study investigated the association between maternal low urinary iodine concentration (UIC) in pregnancy and children's cognition in a population-based sample from a country with an optimal iodine status (the Netherlands). SETTING AND PARTICIPANTS: In 1525 mother–child pairs in a Dutch multiethnic birth cohort, we investigated the relation between maternal UIC<150 μg/g creatinine, assessed <18 weeks gestation and children's cognition. OUTCOMES MEASURES: Non-verbal IQ and language comprehension were assessed during a visit to the research centre using Dutch test batteries when the children were 6 years. RESULTS: In total, 188 (12.3%) pregnant women had UIC<150 μg/g creatinine, with a median UIC equal to 119.3 μg/g creatinine. The median UIC in the group with UIC>150 μg/g creatinine was 322.9 μg/g and in the whole sample 296.5 μg/g creatinine. There was a univariate association between maternal low UIC and children's suboptimum non-verbal IQ (unadjusted OR=1.44, 95% CI 1.02 to 2.02). However, after adjustment for confounders, maternal low UIC was not associated with children's non-verbal IQ (adjusted OR=1.33, 95% CI 0.92 to 1.93). There was no relation between maternal UIC in early pregnancy and children's language comprehension at 6 years. CONCLUSIONS: The lack of a clear association between maternal low UIC and children's cognition probably reflects that low levels of iodine were not frequent and severe enough to affect neurodevelopment. This may result from the Dutch iodine fortification policy, which allows iodised salt to be added to almost all processed food and emphasises the monitoring of iodine intake in the population

Association of gestational maternal hypothyroxinemia and increased autism risk

Objective Transient gestational hypothyroxinemia in rodents induces cortical neuronal migration brain lesions resembling those of autism. We investigated the association between maternal hypothyroxinemia (gestational weeks 6-18) and autistic symptoms in children. Methods The mother-and-child cohort of the Generation R Study (Rotterdam, the Netherlands) began prenatal enrollment between 2002 and 2006. At a mean gestational age of 13.4 weeks (standard deviation = 1.9, range = 5.9-17.9), maternal thyroid function tests (serum thyrotropin [TSH], free thyroxine [fT4], and thyroid peroxidase [TPO] antibodies) were assessed in 5,100 women. We defined severe maternal hypothyroxinemia as fT4 98th percentile and SRS score in the top 5% of the sample (n = 81, 2.0%). Results Severe maternal hypothyroxinemia (n = 136) was associated with an almost 4-fold increase in the odds of having a probable autistic child (adjusted odds ratio = 3.89, 95% confidence interval [CI] = 1.83-8.20, p < 0.001). Using PDP scores, children of mothers with severe hypothyroxinemia had higher scores of autistic symptoms by age 6 years (adjusted B = 0.23, 95% CI = 0.03-0.37); SRS results were similar. No risk was found for children of TPO-antibody-positive mothers (n = 308). Interpretation We found a consistent association between severe, early gestation maternal hypothyroxinemia and autistic symptoms in offspring. Findings are concordant with epidemiological, biological, and experimental data on autism. Although these findings cannot establish causality, they open the possibility of preventive interventions

Polygenic Risk Scores for Developmental Disorders, Neuromotor Functioning During Infancy, and Autistic Traits in Childhood

Background: Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. Methods: In a population-based cohort in The Netherlands (2002–2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9–20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. Results: Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism–based heritability of overall motor development was 20% (SE = .21) and of autistic traits was 68% (SE = .26). The genetic correlation between overall motor development and autistic traits was .35 (SE = .21, p < .001). Conclusions: We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood

Low Urinary Iodine Excretion during Early Pregnancy Is Associated with Alterations in Executive Functioning in Children 1-3

Abstract The rare but deleterious effects of severe iodine deficiency during pregnancy on cognitive functioning of children are well known. Reports on possible associations between mild-to-moderate maternal iodine deficiency and child development, however, are scarce. In a population-based cohort we examined the association between maternal urinary iodine during early pregnancy and executive functioning in children at 4 y of age. In addition, we investigated the modification of this association by maternal diet and thyroid function. During pregnancy, we measured urinary iodine and thyroid hormone concentrations in associated with higher urinary iodine. Thus, low maternal urinary iodine during pregnancy is associated with impaired executive functioning in children. Because these symptoms were subclinical and occurred at an early age, future studies are needed to show whether these children are more vulnerable to develop later clinical disorders

Low Urinary Iodine Excretion during Early Pregnancy Is Associated with Alterations in Executive Functioning in Children 1-3

Abstract The rare but deleterious effects of severe iodine deficiency during pregnancy on cognitive functioning of children are well known. Reports on possible associations between mild-to-moderate maternal iodine deficiency and child development, however, are scarce. In a population-based cohort we examined the association between maternal urinary iodine during early pregnancy and executive functioning in children at 4 y of age. In addition, we investigated the modification of this association by maternal diet and thyroid function. During pregnancy, we measured urinary iodine and thyroid hormone concentrations in associated with higher urinary iodine. Thus, low maternal urinary iodine during pregnancy is associated with impaired executive functioning in children. Because these symptoms were subclinical and occurred at an early age, future studies are needed to show whether these children are more vulnerable to develop later clinical disorders

Early childhood sleep patterns and cognitive development at age 6 years

__Objective__ To explore the association of sleep duration and awakening frequency with cognitive outcomes in young children. __Methods__ Mothers of 2,800 children from the Generation R cohort reported sleep duration and awakenings at children's age 24 months. At age 6 years, validated Dutch measures were used to assess children's nonverbal intelligence and language comprehension. __Results__ We found a nonlinear association of total sleep time at 24 months with nonverbal intelligence (p=0.03) and language comprehension (p=0.04) at 6 years. Toddlers sleeping within the recommended 11-14 hr had more favorable cognitive development compared with both extremes. Frequent awakenings were negatively associated with nonverbal intelligence, but not with verbal comprehension. __Conclusion__ Sleep duration in toddlerhood has an inverted- U-shaped relation with childhood cognitive measures. Frequent awakenings are associated with lower nonverbal intelligence. Given the marked decline in sleep duration and awakenings in toddlerhood, developmental changes of sleep patterns might be important for cognitive development

Cortical Morphology in 6-to 10-Year Old Children With Autistic Traits: A Population-Based Neuroimaging Study

Objective: Recent evidence suggests that symptoms of social impairment in autism spectrum disorder (ASD) form a spectrum that extends into the general population. However, it is unclear whether the neuroanatomy of ASD also shows a similar continuum in the general population. Therefore, the goal of the present study was to investigate the relationship between cortical morphology and autistic traits along a continuum in a large population-based sample of young children. Method: The study included 717 children, aged 6–10 years, who are participants in the Generation R Study, a large population-based cohort. Autistic traits were measured using the Social Responsiveness Scale when the children were approximately 6 years old. High-resolution MRI was obtained, and morphological measures of the cortex, including cortical thickness and gyrification, were quantified brain-wide. Results: Children with more autistic traits showed widespread areas of decreased gyrification. After excluding children with the highest autistic traits and confirmed ASD, the association remained present in a large cluster involving the left hemisphere temporal and precuneus regions. Comparable, but nonsignificant, effects when comparing a small sample of confirmed ASD case subjects with age- and gender-matched control subjects were observed. Conclusions: Differences in cortical morphology related to autistic traits along a continuum in a large population-based sample of school-aged children were found. Part of these differences remained after excluding the most severely affected children. These findings lend support to an extension of the neurobiology of autistic traits to the general population