Assessing the Mental Health of Maltreated Youth with Child Welfare Involvement Using Multi-Informant Reports.

Researchers often question the validity of multi-informant assessments among adolescents with child welfare involvement. Yet, within other clinical populations, prior research finds that multi-informant reports have a discernable structure characterized by discrete patterns of agreement and disagreement. This structure "tracks" contextual displays of behavior and clinical severity. We examined the structure of multi-informant reports (i.e., adolescent, caregiver, teacher) of adolescent externalizing and internalizing problems in a sample of adolescents with a history of child welfare involvement. Across problem domains and informants, reporting patterns mirrored those observed in other clinical populations, and displayed characteristics robustly present in meta-analytic work on cross-informant correspondence. Specifically, informants agreed more on reports of externalizing problems than internalizing problems and caregiver-teacher dyads agreed more than adolescent-caregiver dyads. Overall, we found robust, replicable patterns of multi-informant reports among child welfare involved adolescents. These reporting patterns may facilitate use and interpretation of multi-informant evidence-based assessments among this population.

Seizures in Children With Severe Traumatic Brain Injury.

OBJECTIVE: Traumatic brain injury causes substantial morbidity and mortality in children. Posttraumatic seizures may worsen outcomes after traumatic brain injury. Posttraumatic seizures risk factors are not completely understood. Our objective was to clarify posttraumatic seizures risk factors in a large cohort of children with severe traumatic brain injury. DESIGN: Retrospective cohort study of a probabilistically linked dataset from the National Trauma Data Bank and the Pediatric Health Information Systems database, 2007-2010. SETTING: Twenty-nine U.S. children's hospitals. PATIENTS: A total of 2,122 children (age, < 18 yr old at admission) with linked National Trauma Data Bank and Pediatric Health Information Systems records, severe (emergency department Glasgow Coma Scale, < 8) traumatic brain injury, hospital length of stay more than 24 hours, and nonmissing disposition. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The outcome was posttraumatic seizures, identified using validated International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Prespecified candidate predictors of posttraumatic seizures included age, injury mechanism, emergency department Glasgow Coma Scale, intracranial hemorrhage type, hypoxia, hypotension, and cardiac arrest. Posttraumatic seizures were diagnosed in 25.2% of children with severe traumatic brain injury. In those without abuse/assault or subdural hemorrhage, the posttraumatic seizures rate varied between 36.6% in those less than 2 years old and 16.4% in those 14-17 years old. Age, abusive mechanism, and subdural hemorrhage are each significant predictors of posttraumatic seizures. The risk of posttraumatic seizures has a complex relationship with these predictors. The estimated odds of posttraumatic seizures decrease with advancing age, odds ratio equal to 0.929 (0.905-0.954) per additional year of age with no abuse/assault and no subdural hemorrhage; odds ratio equal to 0.820 (0.730-0.922) per additional year of age when abuse and subdural hemorrhage are present. An infant with accidental traumatic brain injury and subdural hemorrhage has approximately the same estimated probability of posttraumatic seizures as an abused infant without subdural hemorrhage (47% [95% CI, 39-55%] vs 50% [95% CI, 41-58%]; p = 0.69). The triad of young age, injury by abuse/assault, and subdural hemorrhage confers the greatest estimated probability for posttraumatic seizures (60% [95% CI, 53-66%]). CONCLUSIONS: Posttraumatic seizures risk in children with severe traumatic brain injury is greatest with a triad of younger age, injury by abuse/assault, and subdural hemorrhage. However, posttraumatic seizures are common even in the absence of these factors.

The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

Because educational achievement at the end of compulsory schooling represents a major tipping point in life, understanding its causes and correlates is important for individual children, their families, and society. Here we identify the general ingredients of educational achievement using a multivariate design that goes beyond intelligence to consider a wide range of predictors, such as self-efficacy, personality, and behavior problems, to assess their independent and joint contributions to educational achievement. We use a genetically sensitive design to address the question of why educational achievement is so highly heritable. We focus on the results of a United Kingdom-wide examination, the General Certificate of Secondary Education (GCSE), which is administered at the end of compulsory education at age 16. GCSE scores were obtained for 13,306 twins at age 16, whom we also assessed contemporaneously on 83 scales that were condensed to nine broad psychological domains, including intelligence, self-efficacy, personality, well-being, and behavior problems. The mean of GCSE core subjects (English, mathematics, science) is more heritable (62%) than the nine predictor domains (35-58%). Each of the domains correlates significantly with GCSE results, and these correlations are largely mediated genetically. The main finding is that, although intelligence accounts for more of the heritability of GCSE than any other single domain, the other domains collectively account for about as much GCSE heritability as intelligence. Together with intelligence, these domains account for 75% of the heritability of GCSE. We conclude that the high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

EEG Monitoring and Antiepileptic Drugs in Children with Severe TBI.

BACKGROUND: Traumatic brain injury (TBI) causes substantial morbidity and mortality in US children. Post-traumatic seizures (PTS) occur in 11-42% of children with severe TBI and are associated with unfavorable outcome. Electroencephalographic (EEG) monitoring may be used to detect PTS and antiepileptic drugs (AEDs) may be used to treat PTS, but national rates of EEG and AED use are not known. The purpose of this study was to describe the frequency and timing of EEG and AED use in children hospitalized after severe TBI. METHODS: Retrospective cohort study of 2165 children at 30 hospitals in a probabilistically linked dataset from the National Trauma Data Bank (NTDB) and the Pediatric Health Information Systems (PHIS) database, 2007-2010. We included children (age <18 years old at admission) with linked NTDB and PHIS records, severe (Emergency Department [ED] Glasgow Coma Scale [GCS] <8) TBI, hospital length of stay >24 h, and non-missing disposition. The primary outcomes were EEG and AED use. RESULTS: Overall, 31.8% of the cohort had EEG monitoring. Of those, 21.8% were monitored on the first hospital day. The median duration of EEG monitoring was 2.0 (IQR 1.0, 4.0) days. AEDs were prescribed to 52.0% of the cohort, of whom 61.8% received an AED on the first hospital day. The median duration of AED use was 8.0 (IQR 4.0, 17.0) days. EEG monitoring and AED use were more frequent in children with known risk factors for PTS. EEG monitoring and AED use were not related to hospital TBI volume. CONCLUSION: EEG use is relatively uncommon in children with severe TBI, but AEDs are frequently prescribed. EEG monitoring and AED use are more common in children with known risk factors for PTS.

An Exploratory Association Study of Alcohol Use Disorder and DNA Methylation.

BACKGROUND: Epigenetic factors, including DNA methylation, play an important role in the etiology of alcohol use disorders (AUDs). Noncandidate-based methylome-wide studies leveraging multiple tissue types are needed in order to identify a set of CpG targets that reliably differentiate AUD patients from controls and strongly correlate across brain tissue and more commonly collected tissue types (e.g., buccal cells). METHODS: Postmortem precuneus brain tissue samples were collected from 49 alcohol-dependent (AD) cases and 47 controls (sample I), and DNA was extracted from precuneus and putamen brain tissue and buccal cells in 24 postmortem subjects (sample II). Methylation levels were analyzed at over 450,000 CpG sites in both samples. CpGs that demonstrated significant methylation differences between cases and controls were advanced for further analysis with the goal of identifying CpGs that also demonstrated consistent methylation correlations across tissue type. RESULTS: In the primary analysis, 244 hypomethylated and 188 hypermethylated CpGs met a priori criteria for both significant methylation differences between cases and controls as well as significant correlation across brain and buccal cell tissue types, employing stringent Bonferroni p-value correction. Many of these CpGs were involved in gene networks related to lipid metabolism, immune response, inflammatory response/disease, and gastro-intestinal disease. CONCLUSIONS: More than 400 CpGs demonstrated differences in methylation between AD cases and controls and showed significant correlation across tissue types. Several genes and pathways (e.g., inflammation and immune functioning) that have been previously associated with AUD were identified in the current analyses.

Methylation of a CpG site near the ALDH1A2 gene is associated with loss of control over drinking and related phenotypes.

BACKGROUND: The pathophysiology of alcohol use disorders (AUDs) may be influenced by epigenetics processes such as DNA methylation, but the identification of DNA methylation patterns associated with AUDs has largely been limited to a handful of candidate genes. METHODS: Participants were hazardous drinkers from the local community (n = 309). All participants completed a baseline clinical interview in which they reported on their loss of control over drinking. A subsample participated in an ethanol (EtOH) infusion experiment (n = 50). DNA was extracted from saliva samples and assayed on the Illumina Infinium HumanMethylation27 DNA Analysis BeadChip. RESULTS: We identified significant associations between loss of control over drinking and DNA methylation at multiple CpG sites. In follow-up analyses of one of our top results, a CpG site near the ALDH1A2 gene, we found that methylation was negatively associated with rate of intoxication and self-reported feelings of intoxication, consistent with the view that DNA methylation at ALDH1A2 may be associated with changes in alcohol metabolism. CONCLUSIONS: While these findings require replication, they provide evidence that DNA methylation at multiple CpG sites is associated with loss of control over drinking. It may be useful to examine DNA methylation patterns using several related phenotypes to establish the biological coherence of results and to help prioritize markers for further study.

Word reading fluency: role of genome-wide single-nucleotide polymorphisms in developmental stability and correlations with print exposure.

The genetic effects on individual differences in reading development were examined using genome-wide complex trait analysis (GCTA) in a twin sample. In unrelated individuals (one twin per pair, n = 2,942), the GCTA-based heritability of reading fluency was ~20%-29% at ages 7 and 12. GCTA bivariate results showed that the phenotypic stability of reading fluency from 7 to 12 years (r = 0.69) is largely driven by genetic stability (genetic r = 0.69). Genetic effects on print exposure at age 12 were moderate (~26%) and correlated with those influencing reading fluency at 12 (genetic r = 0.89), indicative of a gene-environment correlation. These findings were largely consistent with quantitative genetic twin analyses that used both twins in each pair (n = 1,066-1,409).

Genetic influence on family socioeconomic status and children's intelligence.

Environmental measures used widely in the behavioral sciences show nearly as much genetic influence as behavioral measures, a critical finding for interpreting associations between environmental factors and children's development. This research depends on the twin method that compares monozygotic and dizygotic twins, but key aspects of children's environment such as socioeconomic status (SES) cannot be investigated in twin studies because they are the same for children growing up together in a family. Here, using a new technique applied to DNA from 3000 unrelated children, we show significant genetic influence on family SES, and on its association with children's IQ at ages 7 and 12. In addition to demonstrating the ability to investigate genetic influence on between-family environmental measures, our results emphasize the need to consider genetics in research and policy on family SES and its association with children's IQ.

TACR1 genotypes predict fMRI response to alcohol cues and level of alcohol dependence.

BACKGROUND: The tachykinin receptor 1 (TACR1) gene is a promising candidate gene in the search for the genetic basis of alcohol dependence (AD); TACR1 antagonists improve symptomology not only in preclinical models of AD but also in a clinical sample of detoxified alcoholics (George et al., Science 319:1536, 2008). The purpose of the current study was to determine whether TACR1 single nucleotide polymorphisms (SNPs) were associated with (i) blood oxygen level dependent (BOLD) activation in response to gustatory alcohol cues in a sample of heavy drinkers and (ii) Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) AD symptom count in a large, publicly available data set-the Study of Addictions: Genetics and Environment Genome Wide Association study (SAGE GWAS) (Bierut et al., 2010). METHODS: First, we examined relationships between TACR1 genotypes and neural responses during a craving task in 326 individuals with alcohol use disorders. Next, correlational analyses between 69 TACR1 SNPs and DSM-IV-TR AD symptoms were performed on the SAGE data set. RESULTS: rs3771863, rs3755459, and rs1106855 predicted BOLD activation in response to alcohol cues in those same reward and reinforcement brain areas, especially in the medial prefrontal cortex, striatum, and insula. rs3771863 also predicted AD symptom count in the SAGE data set and BOLD activation in the mesocorticolimbic pathway response to alcohol cues. CONCLUSIONS: Each of the 5 SNPs in the TACR1 gene that was significantly related to AD severity in the SAGE data set and/or the BOLD response to the craving task is near the 3' or 5' areas of the gene and may therefore be near mutations with potential functional significance. In particular, the potential functional significance of rs1106855 should be explored because of its location within a stop codon.

Physical activity and differential methylation of breast cancer genes assayed from saliva: a preliminary investigation.

PURPOSE: Individuals who exercise are at lower risk for breast cancer and have better post-diagnosis outcomes. The biological mechanisms behind this association are unclear, but DNA methylation has been suggested. METHODS: We developed a composite measure of DNA methylation across 45 CpG sites on genes selected a priori. We examined the association of this measure to self-reported physical activity and objectively measured cardiovascular fitness in a sample of healthy nonsmoking adults (n = 64) in an exercise promotion intervention. RESULTS: Individuals who were more physically fit and who exercised more minutes per week had lower levels of DNA methylation. Those who increased their minutes of physical activity over 12 months experienced decreases in DNA methylation. CONCLUSIONS: DNA methylation may be a mechanism linking exercise and cancer incidence and could serve as a biomarker for behavioral intervention trials. Studies with larger samples, objectively measured exercise, and more cancer-related markers are needed.

The Impact of COVID-19 on Pregnant Women and Children: Recommendations for Health Promotion.

COVID-19 continues to have severe repercussions on children and pregnant women. The repercussions include not only the direct impact of COVID-19 (ie, children getting infected by COVID-19) but also indirect impacts (eg, safeguarding from child maltreatment, obesogenic behaviors, language and socioemotional development, educational consequences [eg, interrupted learning]; social isolation; mental health; behavioral health [eg, increased substance use in adolescence]; health and economic impact of COVID-19 on caregivers and family relationships. It has also shed light on long-standing structural and socioeconomic issues, including equity in nutrition and food security, housing, childcare, and internet access. Using a socioecological, life course, and population health approach, we discuss the implications for pregnant women and children's health and well-being and give recommendations for mitigating the short and long-term deleterious impact COVID- 19 on women, children, and their families.

Mathematics is differentially related to reading comprehension and word decoding: Evidence from a genetically-sensitive design.

Although evidence suggests that individual differences in reading and mathematics skills are correlated, this relationship has typically only been studied in relation to word decoding or global measures of reading. It is unclear whether mathematics is differentially related to word decoding and reading comprehension. The current study examined these relationships at both a phenotypic and etiological level in a population-based cohort of 5162 twin pairs at age 12. Multivariate genetic analyses of latent phenotypic factors of mathematics, word decoding and reading comprehension revealed substantial genetic and shared environmental correlations among all three domains. However, the phenotypic and genetic correlations between mathematics and reading comprehension were significantly greater than between mathematics and word decoding. Independent of mathematics, there was also evidence for genetic and nonshared environmental links between word decoding and reading comprehension. These findings indicate that word decoding and reading comprehension have partly distinct relationships with mathematics in the middle school years.

Associations between reading achievement and independent reading in early elementary school: a genetically informative cross-lagged study.

This study used a cross-lagged twin design to examine reading achievement and independent reading from 10 to 11 years (n = 436 twin pairs). Reading achievement at age 10 significantly predicted independent reading at age 11. The alternative path, from independent reading at age 10 to reading achievement at age 11, was not significant. Individual differences in reading achievement and independent reading at both ages were primarily due to genetic influences. Furthermore, individual differences in independent reading at age 11 partly reflected genetic influences on reading achievement at age 10. These findings suggest that genetic influences that contribute to individual differences in children's reading abilities also influence the extent to which children actively seek out and create opportunities to read.

Two by two: a twin study of second-language acquisition.

In this report, we provide initial results of the first application of the classic twin design to second-language acquisition. The analysis was conducted on assessments teachers made using United Kingdom National Curriculum standards and included 604 pairs of 14-year-old twins. The results demonstrate substantial heritability (.67) and low influence of shared environment (.13) on this measure of second-language acquisition. The heritability of second-language acquisition at 14 years is comparable to the heritability of the two first-language acquisition measures obtained at 12 and 14 years, respectively, and is higher than heritability estimates previously published for first-language acquisition in early childhood. Multivariate behavior genetic analyses suggest very high, but not complete, overlap of genetic influences on first- and second-language acquisition, and less overlap between shared environmental influences on the two domains.

Genetic and environmental influences on the growth of early reading skills.

BACKGROUND: Studies have suggested genetic and environmental influences on overall level of early reading whereas the larger reading literature has shown environmental influences on the rate of growth of early reading skills. This study is the first to examine the genetic and environmental influences on both initial level of performance and rate of subsequent growth in early reading. METHODS: Participants were drawn from the Western Reserve Reading Project, a study of 314 twin pairs based in Ohio. Twins were assessed via three annual home visits during early elementary school. Assessments included word identification, letter identification, pseudoword decoding, expressive vocabulary, phoneme awareness, and rapid naming. Measures were analyzed using latent growth curve modeling. RESULTS: The heritability of initial performance (latent intercept) ranged from h(2) = .38 for word identification to h(2) = .72 for rapid naming. Shared environment ranged from c(2) = .11 for rapid naming to c(2) = .62 for word identification. The heritability of the rate of subsequent growth (latent slope) was statistically significant for rapid naming h(2) = .58 and phoneme awareness h(2) = .20. Shared environment accounted for nearly 100% of variance in rate of growth for word identification, letter identification and pseudoword decoding, and was statistically significant and large for phoneme awareness (c(2) = .80). Genetic variance for rapid naming and phoneme awareness latent slopes overlapped entirely with genetic variance on the intercepts. In contrast, one-third to two-thirds of the shared environmental variance on the slope was independent from the shared environmental variance on the intercept. CONCLUSIONS: Genetic influences were related primarily to those already present at the initial level of performance. In contrast, shared environmental influences affecting rate of growth were both predicted by and independent from initial levels of performance. Results suggested that growth in early reading skills is amenable to family, school, or other environmental influences as reading skills develop.

Common genetic effects of gender atypical behavior in childhood and sexual orientation in adulthood: a study of Finnish twins.

The existence of genetic effects on gender atypical behavior in childhood and sexual orientation in adulthood and the overlap between these effects were studied in a population-based sample of 3,261 Finnish twins aged 33-43 years. The participants completed items on recalled childhood behavior and on same-sex sexual interest and behavior, which were combined into a childhood gender atypical behavior and a sexual orientation variable, respectively. The phenotypic association between the two variables was stronger for men than for women. Quantitative genetic analyses showed that variation in both childhood gender atypical behavior and adult sexual orientation was partly due to genetics, with the rest being explained by nonshared environmental effects. Bivariate analyses suggested that substantial common genetic and modest common nonshared environmental correlations underlie the co-occurrence of the two variables. The results were discussed in light of previous research and possible implications for theories of gender role development and sexual orientation.

More than just IQ: A longitudinal examination of self-perceived abilities as predictors of academic performance in a large sample of UK twins.

This paper examines the longitudinal causal relationship between self-perceived abilities (SPA) and academic achievement (Ach) while controlling for cognitive ability (CA). In all, 5957 UK school children were assessed on SPA, Ach and CA at ages 9 and 12. Results indicated that SPA and Ach at age 9 independently affected both SPA and Ach at age 12, even when CA was considered. Moreover the effects of previous Ach on subsequent SPA were of similar magnitude to the effects of prior SPA on subsequent Ach, suggesting that the link between SPA and Ach independent of CA is reflective of both "insight" (children's accounts of their previous performance) and self-efficacy (the self-fulfilling or motivational effects of self-beliefs). Practical and theoretical implications for the study of SPA are discussed.

More than just IQ: school achievement is predicted by self-perceived abilities--but for genetic rather than environmental reasons.

Evidence suggests that children's self-perceptions of their abilities predict their school achievement even after one accounts for their tested cognitive ability (IQ). However, the roles of nature and nurture in the association between school achievement and self-perceived abilities (SPAs), independent of IQ, is unknown. Here we reveal that there are substantial genetic influences on SPAs and that there is genetic covariance between SPAs and achievement independent of IQ. Although it has been assumed that the origins of SPAs are environmental, this first genetic analysis of SPAs yielded a heritability of 51% in a sample of 3,785 pairs of twins, whereas shared environment accounted for only 2% of the variance in SPAs. Moreover, multivariate genetic analyses indicated that SPAs predict school achievement independently of IQ for genetic rather than environmental reasons. It should therefore be possible to identify "SPA genes" that predict school achievement independently of "IQ genes."

Heritability of high reading ability and its interaction with parental education.

Moderation of the level of genetic influence on children's high reading ability by environmental influences associated with parental education was explored in two independent samples of identical and fraternal twins from the United States and Great Britain. For both samples, the heritability of high reading performance increased significantly with lower levels of parental education. Thus, resilience (high reading ability despite lower environmental support) is more strongly influenced by genotype than is high reading ability with higher environmental support. This result provides a coherent account when considered alongside results of previous research showing that heritability for low reading ability decreased with lower levels of parental education.

Generalist genes and learning disabilities: a multivariate genetic analysis of low performance in reading, mathematics, language and general cognitive ability in a sample of 8000 12-year-old twins.

BACKGROUND: Our previous investigation found that the same genes influence poor reading and mathematics performance in 10-year-olds. Here we assess whether this finding extends to language and general cognitive disabilities, as well as replicating the earlier finding for reading and mathematics in an older and larger sample. METHODS: Using a representative sample of 4000 pairs of 12-year-old twins from the UK Twins Early Development Study, we investigated the genetic and environmental overlap between internet-based batteries of language and general cognitive ability tests in addition to tests of reading and mathematics for the bottom 15% of the distribution using DeFries-Fulker extremes analysis. We compared these results to those for the entire distribution. RESULTS: All four traits were highly correlated at the low extreme (average group phenotypic correlation = .58). and in the entire distribution (average phenotypic correlation = .59). Genetic correlations for the low extreme were consistently high (average = .67), and non-shared environmental correlations were modest (average = .23). These results are similar to those seen across the entire distribution (.68 and .23, respectively). CONCLUSIONS: The 'Generalist Genes Hypothesis' holds for language and general cognitive disabilities, as well as reading and mathematics disabilities. Genetic correlations were high, indicating a strong degree of overlap in genetic influences on these diverse traits. In contrast, non-shared environmental influences were largely specific to each trait, causing phenotypic differentiation of traits.