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Objective: Identify factors contributing to time a family spends in a Multidisciplinary Craniofacial Team Clinic (MDCT) and implement an intervention to reduce this time. Design: Interventional: a restructuring of clinics to serve those patients requiring fewer provider encounters separately. Setting: An American Cleft Palate-Craniofacial Association-accredited MDCT in an academic children’s hospital. Patients/Participants: One hundred sixty-seven patients with craniofacial diagnoses. Interventions: Time data were tabulated over ∼2 years. Following 9 months of data collection, patients requiring fewer provider encounters were scheduled to a separate clinic serving children with craniosynostosis, and data were collected in the same fashion for another 14 months. Main Outcome Measures: Principal outcome measures included total visit time and proportion of the visit spent without a provider in the room before and after clinic restructuring. Results: The average time spent by family in a clinic session was 161.53 minutes, of which 64.3% was spent without a provider in the room. Prior to clinic restructuring, a greater number of provider encounters was inversely associated with percentage of time spent without a provider ( P < .001). Upon identifying this predictor, scheduling patients who needed fewer provider encounters to a Craniosynostosis Clinic session resulted in reduction in absolute and percentage of time spent without a provider ( P < .001). Conclusions: The number of provider encounters is a significant predictor of the proportion of a clinic visit spent without a provider. Clinic restructuring to remove patient visits that comprise fewer provider encounters resulted in a greater percentage of time spent with a provider in an MDCT.

Purpose of Review To examine the evidence that the dietary quality of children changed between the period preceding the COVID-19 pandemic and the first year during the pandemic. Recent Findings A systematic review of the evidence for dietary changes occurring as a result of the pandemic-related restrictions, in Part I of this article, yielded 38 original research articles. These articles had conflicting results, some describing improvements in overall quality and some describing deteriorations. As a whole the studies were characterized by a low study quality, and children were poorly represented. Taken together, these studies do not provide enough evidence to draw conclusions about whether dietary habits changed or not as a result of the pandemic. However, in a wider, narrative review of the psychosocial changes occurring as a result of the COVID-19 pandemic, and the known associations of these factors with a dietary intake in Part II, we conclude that there is a reason to expect that the dietary quality of children might have been adversely affected by the COVID-19 pandemic. Summary One the one hand, the literature fails to provide conclusive evidence on changes in the dietary quality of children resulting from the COVID-19 pandemic. On the other hand, the broader literature supports the hypothesis that children’s dietary quality will have declined during the pandemic. Taken together, we urgently need more high-quality research on children’s changes in dietary intake occurring over the pandemic. This will provide important information on whether any potential long-term consequences of such changes, if they exist, need to be examined and ameliorated.

The pathophysiology underlying pseudotumor cerebri syndrome (PTCS) is complex and not well understood. There are clear differences between PTCS in adults and pediatrics. Few and isolated case reports have suggested that adrenal function may be involved, yet no large cohort study has examined this relationship.We conducted a retrospective single-center study of children who presented with a diagnosis of PTCS and had cortisol testing measured between January 2010 and September 2019. We included all subjects meeting the revised PTCS diagnostic criteria after the chart review. Based on morning, random or 1-μg cosyntropin stimulated cortisol levels, adrenal functioning was classified as: (1) insufficient (peak cortisol16 μg/dL and AM cortisol5 μg/dL), (2) at risk (peak cortisol 16-20 μg/dL, AM cortisol 5-13 μg/dL, or random13 μg/dL), or (3) sufficient (peak cortisol20 μg/dL and AM or random cortisol13 μg/dL).A total of 398 individuals were reviewed, and 64 were included for analysis. Of these, 40.6% were men, of mixed race and ethnicity with a mean age of 10.5 (SD 4.7) years. Of these, 23% and 52% had insufficient or at-risk cortisol levels. The majority of those in the insufficient (70%) or at-risk (80%) groups were exposed to topical, nasal, or inhaled glucocorticoids but not systemic. Only 60% and 12% of those with PTCS with insufficient or at-risk cortisol testing, respectively, underwent definitive testing with a stimulation test.Glucocorticoid use and hypocortisolism are prevalent in PTCS and need consideration as a potential underlying cause. Most children had insufficient or at-risk cortisol levels, and many did not undergo further testing/workup. Children who present with PTCS, particularly young, males should be evaluated for adrenal insufficiency and its risk factors, including nonsystemic steroids. Prospective studies are necessary to further evaluate the effect of cortisol in relation to pediatric PTCS.

BACKGROUND Patients with chiasmatic-hypothalamic low-grade glioma (CHLGG) have frequent MRIs with gadolinium-based contrast agents (GBCA) for disease monitoring. Cumulative gadolinium deposition in the brains of children is a potential concern. The purpose of this study is to evaluate whether MRI with GBCA is necessary for determining radiographic tumor progression in children with CHLGG. METHODS Children who were treated for progressive CHLGG from 2005 to 2019 at Texas Children's Cancer Center were identified. Pre- and post-contrast MRI sequences were separately reviewed by one neuroradiologist who was blinded to the clinical course. Three dimensional measurements and tumor characteristics were evaluated. Radiographic progression was defined as a 25% increase in size (product of two largest dimensions) compared with baseline or best response after initiation of therapy. RESULTS A total of 28 patients with progressive CHLGG were identified with a total of 683 MRIs with GBCA reviewed (mean 24 MRIs/patient; range, 11-43 MRIs). Radiographic progression was observed 92 times, 91 (99%) on noncontrast and 90 (98%) on contrast imaging. Sixty-seven progressions necessitating management changes were identified in all (100%) noncontrast sequences and 66 (99%) contrast sequences. Tumor growth > 2 mm in any dimension was identified in 184/187 (98%) noncontrast and 181/187 (97%) with contrast imaging. Metastatic tumors were better visualized on contrast imaging in 4/7 (57%). CONCLUSION MRI without GBCA effectively identifies patients with progressive disease. When imaging children with CHLGG, eliminating GBCA should be considered unless monitoring patients with metastatic disease.

Background Hypothalamic obesity causes unrelenting weight gain for childhood brain tumor survivors. No single therapy has proven effective for treatment. We aimed to evaluate effectiveness of long-term methylphenidate therapy on body mass index (BMI) change in children with hypothalamic obesity. Methods A retrospective analysis included children with a history of brain tumor and hypothalamic obesity receiving methylphenidate (10-60 mg/day) for hypothalamic obesity. Subjects were evaluated for BMI trajectory before and after methylphenidate start. Given that z-scores can be skewed in severely obese children, we calculated BMI as a percent of the BMI at the 95th percentile for the child's age and gender (BMI% 95th). Results Twelve patients with hypothalamic obesity completed methylphenidate therapy for at least 6 months (median 3.1 years, range 1.0-5.8 years). All subjects had a suprasellar tumor (nine [75%] with craniopharyngioma) and pituitary dysfunction. Pretreatment median BMI percent of the 95th percentile was 125.6% (interquartile range [IQR] 25-75: 115.3-138.3%) with BMI z-score of 2.4 (IQR 25-75: 2.1-2.6). Following methylphenidate treatment, there was a 69.9% reduction in the median slope of BMI change. Eleven of 12 patients (92%) had a reduction in the slope of their BMI change on methylphenidate treatment. Postmethylphenidate median BMI percent of the 95th percentile decrease to 115.2% (IQR 25-75: 103.6-121.2%) with median BMI z-score of 2.1 (IQR 25-75: 1.8-2.2). Mild side effects were noted in six patients. Conclusions Methylphenidate use reduced and sustained BMI change in children with hypothalamic obesity. Stimulant therapy is an effective first-line agent for treatment of hypothalamic obesity.

PURPOSE OF REVIEW: Current feeding advice to prevent pediatric obesity focusses on caregiver feeding behaviors. This review integrates newer data showing that child appetitive traits also have a genetic component. RECENT FINDINGS: Caregiver feeding behaviors robustly correlate with child eating behaviors; however there is also a strong heritable component. SUMMARY: The satiety cascade delineates the biological drive underlying hunger, satiation and satiety. Innate individual differences exist for the components of the satiety cascade, which may explain the heritability of child eating behaviors. However, given the correlation of caregiver feeding behaviors with child eating behaviors any etiological model should include both genetic/biological components and environmental. Integrating the biological etiology of child eating behaviors into the current environmental model has implications for tailoring feeding advice which needs to move from a “one size fits all” approach, to one that is tailored to individual differences in children’s biological drives to appetite.

Background DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific. Results For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues. Conclusions In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease. Electronic supplementary material The online version of this article (10.1186/s13059-019-1708-1) contains supplementary material, which is available to authorized users.

PURPOSE OF REVIEW: This narrative review describes the evidence for both genetic and environmental influences on child appetitive traits, and suggests ways of thinking about how these interact and correlate to influence how a child eats. RECENT FINDINGS: Emerging evidence from social network analysis, and from longitudinal studies questioning the direction of association between parent feeding behaviors and child obesity risk, suggest that children’s genes may shape the environmental risk for obesity that they are exposed to. SUMMARY: There is strong evidence that child appetitive traits are both heritable, and shaped by the environment. Instead of thinking about how genetic and environmental factors operate independently on each appetitive trait, research needs to expand the current paradigm to examine how genes and environments interact and shape each other.

Various policies to reduce sugar-sweetened beverages (SSBs) consumption in children have been implemented. Here, we review the evidence on whether these policies are effective in reducing SSB intake and whether a reduction in SSB intake results in a concomitant reduction in child obesity. We also highlight ethical concerns with such efforts. The evidence supporting relationship between SSB consumption and child body mass index (BMI) is consistently small and lacks causality. The effects of policies are unclear; taxation has no clear relationship to SSB purchasing, innovative marketing outlets make it difficult to examine the effects of restricting marketing on SSB consumption, and there is no evidence that reducing SSB availability in schools decreases consumption. Research studies with rigorous and reproducible study designs are needed to examine whether reducing SSB consumption reduces child obesity, and to identify implementable policies that not only reduce SSB consumption but also child weight.

BACKGROUND Executive functions (EFs) comprise a group of cognitive processes that selectively control and regulate attention. Inverse relations have been reported between EFs and BMI. However, the mechanisms underlying this association are not well understood. OBJECTIVES We aimed to decompose the inverse relation between EFs and BMI into genetic and environmental components. METHODS We employed a cross-sectional analysis of data from 869 twins aged 7-15 y from the Texas Twin Project, who completed a neuropsychological test battery measuring 4 EFs (switching, inhibitory control, working memory, and updating); academic achievement (reading and mathematics); and general cognitive abilities (general intelligence/intelligence quotient; crystallized and fluid intelligence; and processing speed). Participants also had their height and weight measured. RESULTS After controlling for age, sex, and race/ethnicity, BMI was inversely associated with a general EF factor representing the capacity to control and regulate goal-oriented behaviors (r = -0.125; P = 0.01; Q = 0.04). This inverse BMI-EF association was due to a significant overlap in genetic factors contributing to each phenotype (genetic correlation, rA, = -0.15; P

BackgroundTwin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ.MethodMultivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI).ResultsSignificant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ.ConclusionsThe aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Previous studies have documented the primarily genetic aetiology for the stronger phenotypic covariance between reading disability and ADHD inattention symptoms, compared to hyperactivity-impulsivity symptoms. In this study, we examined to what extent this covariation could be attributed to "generalist genes" shared with general cognitive ability or to "specialist" genes which may specifically underlie processes linking inattention symptoms and reading difficulties. We used multivariate structural equation modeling on IQ, parent and teacher ADHD ratings and parent ratings on reading difficulties from a general population sample of 1312 twins aged 7.9-10.9 years. The covariance between reading difficulties and ADHD inattention symptoms was largely driven by genetic (45%) and child-specific environment (21%) factors not shared with IQ and hyperactivity-impulsivity; only 11% of the covariance was due to genetic effects common with IQ. Aetiological influences shared among all phenotypes explained 47% of the variance in reading difficulties. The current study, using a general population sample, extends previous findings by showing, first, that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genes contributing to general cognitive ability and, second, that child-specific environment factors, independent from IQ, also contribute to the covariation between reading difficulties and inattention symptoms.

BackgroundAttention deficit hyperactivity disorder (ADHD) shows a strong phenotypic and genetic association with reaction time (RT) variability, considered to reflect lapses in attention. Yet we know little about whether this aetiological pathway is shared with other affected cognitive processes in ADHD, such as lower IQs or the generally slower responses (mean RTs). We aimed to address the question of whether a shared set of genes exist that influence RT variability, mean RT, IQ and ADHD symptom scores, or whether there is evidence of separate aetiological pathways.MethodMultivariate structural equation modelling on cognitive tasks data (providing RT data), IQ and ADHD ratings by parents and teachers collected on general population sample of 1314 twins, at ages 7–10 years.ResultsMultivariate structural equation models indicated that the shared genetic influences underlying both ADHD symptom scores and RT variability are also shared with those underlying mean RT, with both types of RT data largely indexing the same underlying liability. By contrast, the shared genetic influences on ADHD symptom scores and RT variability (or mean RT) are largely independent of the genetic influences that ADHD symptom scores share with IQ.ConclusionsThe finding of unique aetiological pathways between IQ and RT data, but shared components between mean RT, RT variability and ADHD symptom scores, illustrates key influences in the genetic architecture of the cognitive and energetic processes that underlie the behavioural symptoms of ADHD. In addition, the multivariate genetic model fitting findings provide valuable information for future molecular genetic analyses.

Contains fulltext : 89372.pdf (Publisher’s version ) (Closed access) Burt (2009) recently published a meta-analysis of twin studies on behaviors associated with childhood psychopathologies, concluding that the finding that traits associated with attention-deficit/hyperactivity disorder (ADHD) were the only behaviors that did not show a significant influence of shared environment (C) was surprising. We agree, highlighting four methodological issues that may account for this finding: (a) the use of nonlinear transformations to normalize skewed data; (b) low power to detect C and the subsequent presentation of reduced models; (c) the negative confounding of dominant genetic (D) and C influences in twin models with data exclusively from monozygotic and dizygotic twin pairs reared together; and (d) the correction used for contrast effects (a form of rater bias), which may lead to an overestimate of additive genetic (A) or D parameters at the expense of C. We offer suggestions for future research to address these issues, and we emphasize the need for additional research to examine possible shared environmental factors related to ADHD. 01 mei 2010

Objective Symptoms of overactivity form part of the DSM-IV criteria for the combined or hyperactive-impulsive subtypes of attention-deficit/hyperactivity disorder (ADHD); yet little data exist that would quantify the nature of the overactivity component. We aimed to quantify the ability of four different measures of motion sensor data, taken from actigraphs, and the intraindividual variability (IIV) in these measures, to distinguish ADHD cases from controls. Furthermore, we aimed to investigate the degree of shared familial influences on these measures and the ADHD diagnosis. Method Receiver operating characteristic analysis and multivariate structural equation modeling were used on actigraph data collected during a cognitive testing session in a sample of 116 ADHD combined-type probands, 119 of their siblings, and 218 control siblings (age range 6–18 years). Results Three measures of actigraph data—the number of movements made, the magnitude of these movements, and the IIV in the magnitude of movements—yielded an area under the curve of up to 0.8, indicating an ability to distinguish between cases and controls. The latter two of these measures showed significant shared familial vulnerability with an ADHD diagnosis, with high ADHD-actigraph familial correlations. Conclusions The actigraph data support the DSM-IV conceptualization of including overactivity as one of the core features within ADHD combined subtype. The magnitude of movements made, and the IIV of these movements, may be suitable candidates for future molecular genetic studies seeking to identify polymorphisms associated with the risk for ADHD. Further research should investigate if these findings generalize to a more naturalistic, homelike setting.

Motion sensor devices such as actigraphs are increasingly used in studies that seek to obtain an objective assessment of activity level. They have many advantages, and are useful additions to research in fields such as sleep assessment, drug efficacy, behavior genetics, and obesity. However, questions still remain over the reliability of data collected using actigraphic assessment. We aimed to apply generalizability theory to actigraph data collected on a large, general-population sample in middle childhood, during 8 cognitive tasks across two body loci, and to examine reliability coefficients on actigraph data aggregated across different numbers of tasks and different numbers of attachment loci. Our analyses show that aggregation greatly increases actigraph data reliability, with reliability coefficients on data collected at one body locus during 1 task (.29) being much lower than that aggregated across data collected on two body loci and during 8 tasks (.66). Further increases in reliability coefficients by aggregating across four loci and 12 tasks were estimated to be modest in prospective analyses, indicating an optimum trade-off between data collection and reliability estimates. We also examined possible instrumental effects on actigraph data and found these to be nonsignificant, further supporting the reliability and validity of actigraph data as a method of activity level assessment.

Background: Activity level is an important component of children’s temperament, as well as being part of the core symptom domain of hyperactivity-impulsivity within attention deficit hyperactivity disorder (ADHD). Yet it is poorly understood, due partly to limitations on parent and teacher ratings, which are typically used as measurements of these symptoms. Methods: We aimed to study the etiology of objectively-measured activity level across two situations, using actigraphs. A population-based sample of 463 7–9-year-old twin pairs were assessed individually both when apart undergoing laboratory-based cognitive testing and when together during a break in testing. Results: Heritability of activity level was estimated as 24% during the test session and at 30% during the break in testing. Shared environmental influences accounted for 27% of the variance in activity level during the test session and 42% of activity level measured during the break. A genetic correlation of 1.0 indicated that the same genes influenced activity level across the two situations, justifying the use of a composite measure of the two situations. This produced a heritability estimate of 36%. Conclusions: Objectively-measured activity level shows a moderate degree of genetic influence, with a common set of genes influencing activity level across situations. This supports the use of actigraphs as an additional source of information in studies that aim to improve phenotype definition for molecular genetic studies of activity level and ADHD. Keywords: Activity level, actigraph, etiology, heritability, twin study, genetic effects, attention deficit hyperactivity disorder. Abbreviations: ADHD: attention deficit hyperactivity disorder; CI: confidence interval; MZ: monozygotic; DZ: dizygotic; A: variance due to additive genetic effects; C: variance due to shared environmental effects; E: variance due to child-specific environmental effects; rA: genetic correlation; rC: shared environment correlation; rE: child-specific environment correlation.

Twin studies using both clinical and population-based samples suggest that the frequent co-occurrence of attention deficit hyperactivity disorder (ADHD) and reading ability/disability (RD) is largely driven by shared genetic influences. While both disorders are associated with lower IQ, recent twin data suggest that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genetic influences contributing to general cognitive ability. The current study aimed to extend the previous findings that were based on rating scale measures in a population sample by examining the generalisability of the findings to a clinical population, and by measuring reading difficulties both with a rating scale and with an objective task. This study investigated the familial relationships between ADHD, reading difficulties and IQ in a sample of individuals diagnosed with ADHD combined type, their siblings and control sibling pairs.Multivariate familial models were run on data from 1,789 individuals at ages 6-19. Reading difficulties were measured with both rating scale and an objective task. IQ was obtained using the Wechsler Intelligence Scales (WISC-III/WAIS-III).Significant phenotypic (.2-.4) and familial (.3-.5) correlations were observed among ADHD, reading difficulties and IQ. Yet, 53%-72% of the overlapping familial influences between ADHD and reading difficulties were not shared with IQ.Our finding that familial influences shared with general cognitive ability, although present, do not account for the majority of the overlapping familial influences on ADHD and reading difficulties extends previous findings from a population-based study to a clinically ascertained sample with combined type ADHD.

Attention deficit hyperactivity disorder and oppositional behaviours frequently co-occur, We aimed to study the etiology of this overlap in a general population-based twin sample, assessing the symptom domains of hyperactivity-impulsivity and inattentiveness separately for their overlap with oppositionality. We further aimed to investigate whether rater bias may contribute to the overlap in previous data which used one rater only. Using parent and teacher ratings on hyperactivity-impulsivity, inattentiveness and oppositionality, and actigraph measurements of activity level, for 668 7-9-year-old twin pairs, oppositionality showed a higher overlap with hyperactivity-impulsivity (r = 0.95) than with inattentiveness (r = 0.52) and all etiological influences on hyperactivity-impulsivity were shared with those on oppositionality, indicated by a genetic correlation of 0.95 and a child-specific environmental correlation of 0.94. Actigraph data did not show an overlap with ratings of oppositionality. In middle childhood, symptoms of hyperactivity-impulsivity and oppositional behaviour may represent the same underlying liability, whereas the inattentive domain is more distinct.

Focusing on symptoms of attention deficit hyperactivity disorder (ADHD) in a sample obtained from the general population, we aimed to investigate the effects of incentives and event rate on reaction time (RT) performance and response inhibition. We assessed 1156 children, at a mean age of 8 years, on their performance on an inhibition task and a RT task under different experimental conditions that manipulated event rate and incentives. Children with high ADHD (ADHD-H) symptoms showed cognitive performance deficits only under some of the experimental conditions compared to a control group. The fast-incentive condition of the RT task succeeded in normalizing the RT variability, as well as the slow overall speed, in the ADHD-H group. Analyses of ADHD symptom scores as a quantitative trait in the total sample were overall consistent with these findings. The findings suggest that at least some cognitive performance deficits in children with high ADHD symptoms do not reflect stable cognitive deficits. The degree to which cognitive impairments in ADHD can be modulated by energetic or motivational factors has important implications for clinical and educational interventions. (JINS, 2009, 15, 570–579.)

Despite the high heritability of children's activity level, which forms part of the core symptom domain of hyperactivity-impulsivity within attention deficit hyperactivity disorder (ADHD), there has only been a limited success with identifying candidate genes involved in its etiology. This may reflect a lack of understanding about the different measures used to define activity level across studies. We aimed to study the genetic and environmental etiology across three measures of activity level: parent and teacher ratings of hyperactivity-impulsivity and actigraph measurements, within a population-based sample of 463 7-9 year old twin pairs. We further examined ways in which the three measures could be combined for future molecular studies. Phenotypic correlations across measures were modest, but a common underlying phenotypic factor was highly heritable (92%); as was a simple aggregation of all three measurements (77%). This suggests that distilling what is common to all three measures may be a good method for generating a quantitative trait suitable for molecular studies of activity level in children. The high heritabilities found are encouraging in this respect.

Contains fulltext : 89304.pdf (Publisher’s version ) (Open Access) CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. OBJECTIVES: To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. DESIGN: An ADHD and control sibling-pair design. SETTING: Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. PARTICIPANTS: A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. MAIN OUTCOME MEASURES: Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. RESULTS: The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. CONCLUSIONS: The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions. 01 november 2010