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Background: Peer victimization is associated with a wide range of mental health problems in youth, yet few studies described its association with mental health comorbidities. Methods: To test the association between peer victimization timing and intensity and mental health comorbidities, we used data from 1216 participants drawn from the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Peer victimization was self-reported at ages 6–17 years, and modeled as four trajectory groups: low, childhood-limited, moderate adolescence-emerging, and high-chronic. The outcomes were the number and the type of co-occurring self-reported mental health problems at age 20 years. Associations were estimated using negative binomial and multinomial logistic regression models and adjusted for parent, family, and child characteristics using propensity score inverse probability weights. Results: Youth in all peer victimization groups had higher rates of co-occurring mental health problems and higher likelihood of comorbid internalizing-externalizing problems [odds ratios ranged from 2.06, 95% confidence interval (CI) 1.52–2.79 for childhood-limited to 4.34, 95% CI 3.15–5.98 for high-chronic victimization] compared to those in the low victimization group. The strength of these associations was highest for the high-chronic group, followed by moderate adolescence-emerging and childhood-limited groups. All groups also presented higher likelihood of internalizing-only problems relative to the low peer victimization group. Conclusions: Irrespective of timing and intensity, self-reported peer victimization was associated with mental health comorbidities in young adulthood, with the strongest associations observed for high-chronic peer victimization. Tackling peer victimization, especially when persistent over time, could play a role in reducing severe and complex mental health problems in youth. [ABSTRACT FROM AUTHOR]

Background: Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene–environment interaction using a polygenic risk score for depression (PRS‐depression) in the context of peer victimisation and depressive symptoms in adolescence. Methods: The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12–13 years) obtained from both self‐ and teacher‐reports, as well as self‐reported depressive symptoms (15–17 years). The PRS‐depression was based on the genome‐wide association meta‐analysis of broad depression by Howard et al. (2019). Results: Self‐ and teacher‐reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (β = 0.34, p <.001; β = 0.14, p =.001 respectively), and this association remained significant when accounting for PRS‐depression (β = 0.33, p <.001; β = 0.13, p =.002 respectively). PRS‐depression was independently associated with depressive symptoms, but there was no significant PRS‐depression by peer victimisation interaction (self‐reported and teacher‐reported). PRS‐depression was correlated with self‐reported, but not teacher‐reported, peer victimisation. Conclusions: Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS‐depression, and being exposed to peer victimisation (self‐ and teacher‐reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS‐depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene–environment correlation between PRS‐depression and self‐reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation. [ABSTRACT FROM AUTHOR]

This replication study revisited conclusions from 2 previous investigations (Gauze, Bukowski. AquanAssee, & Sippola, 1996; van Aken & Asendorpf, 1997), which suggested that support from friends buffers against diminished selfresteem arising from poor quality relationships with mothers during the transition into adolescence. The aim of this replication study was to conduct an independent test of these findings with both concurrent and longitudinal data. Concurrent data for replication analyses were drawn from 4 projects. involving a total of 959 boys and 1.119 girls (ages 10 to 14) from Canada and the United States. Three samples reported participant ethnic descent: Africa (12.1 %), Asia (5.696). Europe (65.3%). Latin America ( 12.1%), and Native North America (0.9%). Child and mother reports of mother-child relationship quality assayed (a) maternal social support (in 3 data sets), and (b) family cohesion and adaptability (in 2 data sets). Main effects were replicated but hypothesized buffering effects were not. Maternal social support and friend social support were independently associated with adolescent self-esteem, concurrently, but not longitudinally. Family cohesion (but not adaptability) was associated with adolescent self-esteem. concurrently and longitudinally. Friend social support did not moderate associations between mother-child mla- tionship quality and adolescent self-esteem, concurrently or longitudinally. The findings are consistent with a cumulative effects model wherein friends uniquely contribute to adolescent self-worth, over and above the contribution of mothers. The findings do not support claims that friends moderate associations between mother-child relationship quality and adolescent self-esteem. [ABSTRACT FROM AUTHOR]

Purpose: The Quebec Longitudinal Study of Child Development (QLSCD) was designed to examine the long-term associations of preschool physical, cognitive, social, and emotional development with biopsychosocial development across childhood, adolescence, and young adulthood.Methods: QLSCD is an ongoing prospective cohort including 2120 singletons born in 1997/1998 in the Canadian province of Quebec. So far, data have been collected annually or every 2 years from child ages 5 months to 21 years. The cohort currently includes 1245 participants. Data available include a range of environmental (e.g., family characteristics, child behaviour, educational attainment, mental health), biological (e.g., hair cortisol, genetic, epigenetic), and administrative data.Results: QLSCD has contributed to the understanding of children's psychosocial development, including the development of physical aggression and anxiety. QLSCD articles have advanced scientific knowledge on the influence of early childhood factors on childhood, adolescent, and young adult mental health, including the effect of participation in early childcare on cognitive and behavioural development, the developmental origins of adolescent and young adult mental health problems and suicide risk, and the development of interpersonal difficulties (e.g., peer victimisation) from preschool years to adolescence.Conclusion: QLSCD has given major contributions to our understanding of the link between different aspects of child development and biopsychosocial development during the first two decades of life. Unique features include the presence of environmental, biological, and administrative data, long-term follow-up with frequent data collections, and use of data from multiple informants, including teachers, mothers, fathers, and the children themselves. [ABSTRACT FROM AUTHOR]

Background: Advanced critical care echocardiography (CCE) involves comprehensive assessment of cardiac structure and function for frontline critical care applications. This study reports the effectiveness of a 3-day course in advanced CCE. Methods: We studied the outcome of 5 consecutive advanced CCE courses delivered between 2013 and 2017. A total number of 239 learners were studied. The course included didactic lectures, image interpretation sessions, and hands-on training with normal individuals as models. Training domains included left ventricular structure and function, right ventricular structure and function, valve function using comprehensive 2-dimensional imaging, and Doppler-based measurements for cardiac pressures and flows. Measurements of course outcome included pre- and postcourse assessment of knowledge, image acquisition, and image interpretation skills. Learners rotated between hands-on training and interpretation sessions. The teacher-to-learner ratio was 1:3 during hands-on training. Interpretation sessions consisted of review of normal and abnormal echocardiographic videos with interactive small groups. Learners completed a video-based knowledge assessment examination before and after completion of the course. Hands-on image acquisition skills were tested at the completion of the course during all the years. For years 2016 and 2017, a precourse hands-on skill test was also performed. Results: There was a statistically significant improvement in knowledge and image interpretation skills in the cohort of 239 learners over 5 years of study period. There was improvement in image acquisition skills over the 2-year period when it was measured pre- and postcourse. Conclusions: A 3-day course on advanced CCE resulted in improvement knowledge/image interpretation and hands-on image acquisition skills. Clinical Implications: Advanced CCE has assumed an important place in hemodynamic monitoring of critically ill patients. A course of similar design may facilitate training of frontline clinicians in advanced CCE. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to compare children with persistent versus transient preschool language delay on language, academic, and psychosocial outcomes in elementary school. Method: Children with persistent language delay (n = 30), transient language delay (n = 29), and no language delay (controls; n = 163) were identified from a population-based sample of twins. They were compared on language skills, academic achievement, and psychosocial adjustment in kindergarten and Grades 1, 3, 4, and 6. Results: Children with persistent language delay continued to show language difficulties throughout elementary school. Furthermore, they had academic difficulties, in numeracy, and psychosocial difficulties (attention-deficit/hyperactivity disorder behaviors, externalizing behaviors, peer difficulties) from Grade 1 to Grade 6. Children with transient language delay did not differ from controls on language and academic performance. However, they showed more externalizing behaviors in kindergarten and peer difficulties in Grade 1 than controls. Conclusion: Difficulties at school age are widespread and enduring in those with persistent early language delay but appear specific to psychosocial adjustment in those with transient language delay. [ABSTRACT FROM AUTHOR]

This study documented the etiology contributions between anxiety symptoms (AS) and depressive symptoms (DS) from ages 6–12 years. Teachers assessed AS and DS in 1112 twins at 5 time points. A genetic cross-lagged model was used to estimate genetic/environmental contributions to cross-sectional, cross-age and cross-lag associations. The variance in AS and DS was largely time-specific and more genetic in nature for DS than for AS. Previous DS predicted subsequent DS better than cross-lag or previous common effects, and AS up to age 9 better than previous AS or previous common effects. Thereafter, previous AS predicted subsequent AS. All predictions involved both genetic and unique environment. Suppression effects were found and, when controlled, AS marginally predicted DS from age 7 onward through genetic influences. AS and DS are associated throughout childhood. DS are more stable than AS, and more central to both subsequent AS and DS. AS marginally contribute to subsequent DS. [ABSTRACT FROM AUTHOR]

This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child's environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene-environment transactions in development. [ABSTRACT FROM AUTHOR]

Little is known about the development of number knowledge (NK) and the antecedents of low-persistent NK profiles in early childhood. We documented the developmental trajectories of NK across the transition from preschool to elementary school, their predictive validity with respect to later math achievement, and the child and family early-life factors associated with low NK profiles. Children's NK was assessed four times at regular intervals between the ages 4 and 7 years in a large, representative population-based sample. Developmental trajectories of NK were established for 1597 children. These children were also assessed with respect to several features of their family environment at 5, 17, and 29 months, as well as their cognitive skills at age 41 months. Analyses revealed a best-fitting 4-trajectory model, characterized by Low-Increasing (10% of the children), Moderate-Increasing (39%), Moderate-Fast Increasing (32%) and High-Increasing (19%) groups. Children of these trajectory groups differed significantly with respect to math achievement at ages 8 and 10 years, with the Low-Increasing group persistently scoring lower than the other groups throughout these years. Children of Low-Increasing NK group were from household of lower income and father with low educational background, poorer early cognitive development, and more importantly, reduced visual-spatial skills and memory-span. Children displaying reduced cognitive abilities and impoverished living conditions early in life are at greater risk of low NK throughout late preschool and school entry, with ensuing difficulties in math achievement. They deserve early preventive attention to help alleviate later mathematic difficulties. [ABSTRACT FROM AUTHOR]

Background: Exposure to peer victimization is relatively common. However, little is known about its developmental course and its effect on impairment associated with mental illnesses. We aimed to identify groups of children following differential trajectories of peer victimization from ages 6 to 13 years and to examine predictive associations of these trajectories with mental health in adolescence.Methods: Participants were members of the Quebec Longitudinal Study of Child Development, a prospective cohort of 2120 children born in 1997/98 who were followed until age 15 years. We included 1363 participants with self-reported victimization from ages 6 to 13 years and data available on their mental health status at 15 years.Results: We identified 3 trajectories of peer victimization. The 2 prevailing groups were participants with little or moderate exposure to victimization (441/1685 [26.2%] and 1000/1685 [59.3%], respectively); the third group (244 [14.5%]) had been chronically exposed to the most severe and long-lasting levels of victimization. The most severely victimized individuals had greater odds of reporting debilitating depressive or dysthymic symptoms (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.27-5.17), debilitating generalized anxiety problems (OR 3.27, CI 1.64-6.51) and suicidality (OR 3.46, CI 1.53-7.81) at 15 years than those exposed to the lowest levels of victimization, after adjustment for sex, childhood mental health, family hardship and victimization perpetration. The association with suicidality remained significant after controlling for concurrent symptoms of depression or dysthymia and generalized anxiety problems.Interpretation: Adolescents who were most severely victimized by peers had an increased risk of experiencing severe symptoms consistent with mental health problems. Given that peer victimization trajectories are established early on, interventions to reduce the risk of being victimized should start before enrolment in the formal school system. [ABSTRACT FROM AUTHOR]

This study aims to test cognitive skills underlying the association between inattention and reading in early primary school. Teachers rated inattention symptoms when children (N = 523–962) were 6–7 years old. Children were assessed at age 7–8 on phonological awareness, rapid automatized naming (RAN), rapid auditory and bimodal processing, vocabulary, and reading (decoding and comprehension). Phonological awareness, RAN of numbers, and vocabulary mediated the association between inattention and both decoding and comprehension. Rapid bimodal processing mediated the association between inattention and decoding, while RAN of colors mediated the association between inattention and comprehension. This study highlights mediators underlying inattention-reading associations. [ABSTRACT FROM PUBLISHER]

This study investigated the stable and transient genetic and environmental contributions to individual differences in number knowledge in the transition from preschool (age 5) to Grade 1 (age 7) and to the predictive association between early number knowledge and later math achievement (age 10-12). We conducted genetic simplex modeling across these three time points. Genetic variance was transmitted from preschool number knowledge to late-elementary math achievement; in addition, significant genetic innovation (i.e., new influence) occurred at ages 10 through 12 years. The shared and nonshared environmental contributions decreased during the transition from preschool to school entry, but shared and nonshared environment contributed to the continuity across time from preschool number knowledge to subsequent number knowledge and math achievement. There was no new environmental contribution at time points subsequent to preschool. Results are discussed in light of their practical implications for children who have difficulties with mathematics, as well as for preventive intervention. [ABSTRACT FROM AUTHOR]

Multiple studies have shown that reading abilities and attention-deficit/hyperactivity disorder symptoms, mainly inattention symptoms, are phenotypically and genetically associated during childhood. However, few studies have looked at these associations during adolescence to investigate possible developmental changes. The aim of the study is to examine the genetic and environmental etiology of the associations between inattention and hyperactivity reported by parents, and reading accuracy, reading speed, and word reading in a population-based twin sample (Quebec Newborn Twin Study). Participants were between 14 and 15 years of age at the time of testing (N = 668–837). Phenotypic results showed that when nonverbal and verbal abilities were controlled, inattention, but not hyperactivity/impulsivity, was a modest and significant predictor of reading accuracy, reading speed, and word reading. The associations between inattention and all reading abilities were partly explained by genetic and unique environmental factors. However, the genetic correlations were no longer significant after controlling for verbal abilities. In midadolescence, inattention is the attention-deficit/hyperactivity disorder dimension associated with reading abilities, but they could also share genetic factors with general verbal skills. [ABSTRACT FROM AUTHOR]

Background: Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age. Method: Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male) recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus. Results: There were substantial and similar heritability (approximately 31%) and shared environmental (57.3%) contributions to negative emotionality at both 5 and 18 months. The trait’s interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months) indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months. Conclusions: In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology. [ABSTRACT FROM AUTHOR]

Purpose: Poverty has been associated with high levels of behavior problems across childhood, yet patterns of associations over time remain understudied. This study aims: (a) to examine whether poverty predicts changes in behavior problems between 1.5 and 8 years of age; (b) to estimate potential selection bias for the observed associations.Methods: We used the 1998-2006 waves of the Quebec Longitudinal Study of Child Development (N = 2120). Main outcomes were maternal ratings of hyperactivity, opposition and physical aggression from 1.5 to 8 years of age. Linear mixed-effects models were used to assess the longitudinal association between poverty and behavior problems. Models were re-estimated adjusting for wave nonresponse and using multiple imputation to account for attrition.Results: Poverty predicted higher levels of behavior problems between 1.5 and 8 years of age. Poverty predicted hyperactivity and opposition in a time dependent manner. Hyperactivity [Bpoverty*age = 0.052; CI 95 % (0.002; 0.101)] and opposition [Bpoverty*age = 0.049; CI 95 % (0.018; 0.079)] increased at a faster rate up to age 5 years, and then decreased at a slower rate for poor than non-poor children. Physical aggression decreased at a steady rate over time for all children [Bpoverty*age = -0.030; p = 0.064). Estimates remained similar when accounting for attrition.Conclusion: Poverty predicted higher levels of behavior problems between 1.5 and 8 years of age. The difference between poor and non-poor children was stable over time for physical aggression, but increased with age for hyperactivity and opposition. Attrition among poor children did not compromise the validity of results. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections and infected fluid collections are the result of local infection typically involving the gastrointestinal or genitourinary tract. These infections are usually polymicrobial. The management of such patients should include source control and appropriate antimicrobial therapy. Source control is essential and can be achieved either surgically or by percutaneous drainage of intra-abdominal fluid collection. Interventional radiology drainage of intra-abdominal fluid collections may be especially important in patients with high surgical risk or in patients who refuse surgery. Below, we present a case of successful use of recombinant intraperitoneal tissue plasminogen activator use in a patient with a complex polymicrobial fluid collection. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore if child-care intensity (hours/weeks) and age of onset could moderate genetic and environmental contributions to school readiness. A sample of 648 (85% Whites; 50% Females) pairs of twins was used to compute a GxE, CxE and ExE interaction analyses. The moderation model showed that shared environment explains 48% of individual differences in school readiness for children not attending formal child-care, and decreased gradually to a mere 3% for children attending formal child-care full time, e.g., 40 h per week. Age of onset exerted no moderation effect. The results support the hypothesis that child-care acts as a normalizing environment, possibly buffering negative effects from low-quality home environments on school readiness. [ABSTRACT FROM AUTHOR]

Comorbidity is frequent among disruptive behaviors (DB) and leads to mental health problems during adolescence and adulthood. However, the early developmental origins of this comorbidity have so far received little attention. This study investigated the developmental comorbidity of three DB categories during early childhood: hyperactivity-impulsivity, non-compliance, and physical aggression. Joint developmental trajectories of DB were identified based on annual mother interviews from age 1½ to 5 years, in a population-representative birth-cohort (N = 2045). A significant proportion of children (13 % to 21 %, depending on the type of DB) consistently displayed high levels of hyperactivity-impulsivity, non-compliance, or physical aggression from age 1½ to 5 years. Developmental comorbidity was frequent, especially for boys: 10 % of boys and 3.7 % of girls were on a stable trajectory with high levels of symptoms for the three categories of DB. Significant associations were observed between preschool joint-trajectories of DB and indicators of DB and school adjustment assessed by teachers in first grade. Preschoolers who maintained high levels of hyperactivity-impulsivity, non-compliance, and physical aggression, displayed the highest number of DB symptoms in first grade for all categories according to their teacher. They were also among the most disadvantaged of their class for school adjustment indicators. Thus, DB manifestations and developmental comorbidity of DB are highly prevalent in infancy. Early childhood appears to be a critical period to prevent persistent and comorbid DB that leads to impairment at the very beginning of school attendance and to long-term serious health and social adjustment problems. [ABSTRACT FROM AUTHOR]

Objective: To test whether adolescents who are victimized by peers are at heightened risk for suicidal ideation and suicide attempt, using both cross-sectional and prospective investigations.Method: Participants are from the Quebec Longitudinal Study of Child Development, a general population sample of children born in Quebec in 1997 through 1998 and followed up until 15 years of age. Information about victimization and serious suicidal ideation and suicide attempt in the past year was obtained at ages 13 and 15 years from self-reports (N = 1,168).Results: Victims reported concurrently higher rates of suicidal ideation at age 13 years (11.6-14.7%) and suicide attempt at age 15 years (5.4-6.8%) compared to those who had not been victimized (2.7-4.1% for suicidal ideation and 1.6-1.9% for suicide attempt). Being victimized by peers at 13 years predicted suicidal ideation (odds ratio [OR] = 2.27; 95% CI = 1.25-4.12) and suicide attempt (OR = 3.05, 95% CI = 1.36-6.82) 2 years later, even after adjusting for baseline suicidality and mental health problems and a series of confounders (socioeconomic status, intelligence, family's functioning and structure, hostile-reactive parenting, maternal lifetime suicidal ideation/suicide attempt). Those who were victimized at both 13 and 15 years had the highest risk of suicidal ideation (OR = 5.41, 95% CI = 2.53-11.53) and suicide attempt (OR = 5.85, 95% CI = 2.12-16.18) at 15 years.Conclusion: Victimization is associated with an increased risk of suicidal ideation and suicide attempt over and above concurrent suicidality and prior mental health problems. The longer the history of victimization, the greater the risk. [ABSTRACT FROM AUTHOR]

This study examined the associations between intrinsic motivation and achievement in mathematics in a sample of 1,478 Canadian school-age children followed from Grades 1 to 4 (ages 7-10). Children self-reported their intrinsic motivation toward mathematics, whereas achievement was measured through direct assessment of mathematics abilities. Cross-lagged models showed that achievement predicted intrinsic motivation from Grades 1 to 2, and from Grades 2 to 4. However, intrinsic motivation did not predict achievement at any time. This developmental pattern of association was gender invariant. Contrary to the hypothesis that motivation and achievement are reciprocally associated over time, our results point to a directional association from prior achievement to subsequent intrinsic motivation. Results are discussed in light of their theoretical and practical implications. [ABSTRACT FROM AUTHOR]

Background The phenotypic and genetic associations between decoding skills and ADHD dimensions have been documented but less is known about the association with reading comprehension. The aim of the study is to document the phenotypic and genetic associations between reading comprehension and ADHD dimensions of inattention and hyperactivity/impulsivity in early schooling and compare them to those with decoding skills. Methods Data were collected in two population-based samples of twins (Quebec Newborn Twin Study - QNTS) and singletons (Quebec Longitudinal Study of Child Development - QLSCD) totaling ≈ 2300 children. Reading was assessed with normed measures in second or third grade. Teachers assessed ADHD dimensions in kindergarten and first grade. Results Both decoding and reading comprehension were correlated with ADHD dimensions in a similar way: associations with inattention remained after controlling for the other ADHD dimension, behavior disorder symptoms and nonverbal abilities, whereas associations with hyperactivity/impulsivity did not. Genetic modeling showed that decoding and comprehension largely shared the same genetic etiology at this age and that their associations with inattention were mostly explained by shared genetic influences. Conclusion Both reading comprehension and decoding are uniquely associated with inattention through a shared genetic etiology. [ABSTRACT FROM AUTHOR]

This study assessed the genetic and environmental contributions to peer difficulties in the early school years. Twins' peer difficulties were assessed longitudinally in kindergarten (796 twins, Mage = 6.1 years), Grade 1 (948 twins, Mage = 7.1 years), and Grade 4 (868 twins, Mage = 10 years) through multiple informants. The multivariate results revealed that genetic factors accounted for a strong part of both yearly and stable peer difficulties. At the univariate level, the genetic contributions emerged progressively, as did a growing consensus among informants with respect to those who experienced peer difficulties. These results underline the need to intervene early and persistently, and to target the child and the peer context to prevent peer difficulties and their consequences. [ABSTRACT FROM AUTHOR]

The Quebec Newborn Twin Study (QNTS) is an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early bio-social determinants, as well as their putative role in later social-emotional adjustment, school and health outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS has 14 waves of data collected or planned, including 5 in preschool. Over the past 15 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multi-method measurements. QNTS also entails extended and detailed multi-level assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child's environment. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene-environment transactions in development. [ABSTRACT FROM AUTHOR]

Background: A web-based inventory was developed as a voluntary registry of Canadian pregnancy and birth cohort studies, with the objective to foster collaboration and sharing of research tools among cohort study groups as a means to enrich research in maternal and child health across Canada. Description: Information on existing birth cohort studies conducted in Canada exclusively or as part of broader international initiatives was accessed by searching the literature in PubMed and PsychInfo databases. Additional studies were identified by enquiring about the research activities of researchers at Canadian universities or working in affiliated hospitals or research centres or institutes. Of the fifty-eight birth cohort studies initially identified, forty-six were incorporated into the inventory if they were of a retrospective and/or prospective longitudinal design and with a minimum of two phases of data collection, with the first period having occurred before, during, or shortly after pregnancy and had an initial study sample size of a minimum of 200 participants. Information collected from each study was organized into four main categories: basic information, data source and period of collection, exposures, and outcome measures and was coded and entered into an Excel spreadsheet. The information incorporated into the Excel spreadsheet was double checked, completed when necessary, and verified for completeness and accuracy by contacting the principal investigator or research coordinator. All data collected were then uploaded onto the website of the Institute of Human Development Child and Youth Health of the Canadian Institutes of Health Research. Subsequently, the database was updated and developed as an online searchable inventory on the website of the Maternal, Infant, Child and Youth Research Network. Conclusions: This inventory is unique, as it represents detailed information assembled for the first time on a large number of Canadian birth cohort studies. Such information provides a valuable resource for investigators in the planning stages of cohort studies and identifying current research gaps. [ABSTRACT FROM AUTHOR]

Aggressive behavior in middle childhood is at least partly explained by genetic factors. Nevertheless, estimations of simple effects ignore possible gene-environment interactions (G × E) or gene-environment correlations (rGE) in the etiology of aggression. The present study aimed to simultaneously test for G × E and rGE processes between aggression, on the one hand, and peer victimization and the teacher-child relationship in school, on the other hand. The sample comprised 124 MZ pairs and 93 DZ pairs assessed in Grade 1 (mean age = 84.7 months). Consistent with rGE, children with a presumed genetic disposition for aggression were at an increased risk of peer victimization, whereas in line with G × E, a positive relationship with the teacher mitigated the genetically mediated expression of aggression. [ABSTRACT FROM AUTHOR]

Callous-unemotional (CU) traits are associated with antisocial and delinquent behaviors in children and represent a potential risk factor for adult psychopathy. However, there is a paucity of longitudinal research that explores the development of these traits, their longitudinal association with conduct problems (CP), and their psychosocial predictors and outcomes. Using a large sample of children followed longitudinally from the Twins Early Development Study (N = 9,578), we described the joint developmental trajectories of CU traits and CP during childhood (between ages 7 and 12) and examined the child- and family-level predictors (4 years old) and concomitant outcomes (12 years old) associated with the trajectories. The developmental trajectories were characterized with teachers' ratings of CU traits and CP from ages 7 to 12. Using general growth mixture modeling, we identified four trajectories of CU traits (stable high, increasing, decreasing, and stable low) and two trajectories of CP (high and low). Compared with the children who followed a low trajectory of CU traits and CP, those who followed a high trajectory of CU traits and CP had more negative child- and family-level predictors at 4 years (including CP, hyperactivity, negative parental discipline, and chaos in the home). Children with high or increasing levels of CU traits and concomitant high levels of CP presented the most negative outcomes at 12 years (including hyperactivity, peer problems, emotional problems, and negative parental feelings). Children with high CU traits and concomitant high levels of CP in childhood should be prioritized for targeted intervention. [ABSTRACT FROM AUTHOR]

Disregard for rules, a key component of oppositional defiant and conduct disorders, is stable during early childhood. This study investigates for the first time the relative importance of genetic and environmental factors underlying this early developmental stability. Maternal reports of child disregard for rules were obtained at four time points from 20 to 64 months of age in a population-based twin sample (N = 597 twin pairs, including 238 monozygotic and 359 dizygotic pairs). Structural equation modeling was conducted using both variance-covariance and latent growth curve approaches. Genetic factors accounted for most of the stability in disregard for rules throughout early childhood. In contrast, most environmental effects were age specific. Developmental stability in early symptoms of disregard for rules is best explained by the stable action of genetic factors, suggesting that preventive interventions should take an intergenerational approach, targeting at-risk families as early as possible. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2010; 40 (10): 903–910 Background and Objective Muscle atrophy in end-stage renal disease (ESRD) may be due to the activation of apoptotic and proteolytic pathways. We hypothesized that activation of caspase-3 in the skeletal muscle mediates apoptosis and proteolysis during haemodialysis (HD). Materials and Methods Eight ESRD patients were studied before (pre-HD) and during HD and the findings were compared with those from six healthy volunteers. Protein kinetics was determined by primed constant infusion of L-(ring 13C6) Phenylalanine. Results Caspase-3 activity in the skeletal muscle was higher in ESRD patients pre-HD than in controls (24966·0 ± 4023·9 vs. 15293·3 ± 2120·0 units, P < 0·01) and increased further during HD (end-HD) (37666·6 ± 4208·3 units) ( P < 0·001). Actin fragments (14 kDa) generated by caspase-3 mediated cleavage of actomyosin was higher in the skeletal muscle pre-HD (68%) and during HD (164%) compared with controls. The abundance of ubiquitinized carboxy-terminal actin fragment was also significantly increased during HD. Skeletal muscle biopsies obtained at the end of HD exhibited augmented apoptosis, which was higher than that observed in pre-HD and control samples ( P < 0·001). IL-6 content in the soluble fraction of the muscle skeletal muscle was increased significantly during HD. Protein kinetic studies showed that catabolism was higher in ESRD patients during HD compared with pre-HD and control subjects. Muscle protein catabolism was positively associated with caspase-3 activity and skeletal muscle IL-6 content. Conclusion Muscle atrophy in ESRD may be due to IL-6 induced activation of caspase-3 resulting in apoptosis as well as muscle proteolysis during HD. [ABSTRACT FROM AUTHOR]

This study investigated the evolving relations between peer victimization and social/emotional difficulties in middle to late childhood. Peer assessments of peer victimization and social/emotional difficulties (aggressive behavior, social withdrawal, and emotional vulnerability) were collected over 4 years for 1,035 children attending Grades 3-6 and were analyzed via cross-lagged panels and trajectory analyses. All dimensions were highly stable and significantly related initially. Peer victimization became progressively less related to aggression and increasingly associated with withdrawal. Bidirectional contributions over 1-year periods were found between withdrawal and emotional vulnerability and victimization. Trajectory analyses revealed heterogeneity in peer victimization patterns, with a small group of children (4.5%) being extremely victimized and with another group (10%), less severely, but increasingly victimized over time. Compared to nonvictimized children, these children were generally more emotional and became less aggressive but more socially withdrawn over time. These small behavioral changes were not associated with decreases in victimization. [ABSTRACT FROM AUTHOR]

Abstract: A longitudinal study of maternal self-efficacy (SE) and hostile-reactive parenting (HRP) was conducted with a community sample of 1836 mothers. Mothers completed questionnaires when their child was 4.5, 16.6 and 28.5 months of age. Maternal SE showed little change, whereas HRP sharply increased from 4.5 to 28.5 months. Structural equation models suggest these initially correlated variables did not influence each other over time, but rather became increasingly independent. Three distinct developmental trajectories were fitted for both maternal SE and HRP. In contrast to the overall portrait of stability, 12.6% of mothers followed a trajectory of declining SE. Likewise, 12.1% of mothers showed initially high and sharply increasing HRP. Few mothers (3.1%) simultaneously followed both of these trajectories, yet overall, SE and HRP trajectories were modestly associated (τ b =−.23, p <.0001). Failure to support the expected reciprocal influences between SE and HRP over time, as well as maternal and child contributions to early manifestations of maternal HRP and their evolution are discussed. [Copyright &y& Elsevier]

Background: Disregard for rules, an important dimension of oppositional defiant and conduct disorders, is frequent during early childhood, but the development of its chronic form has not been studied during this key socialization period. This study aimed to describe the developmental trajectories of disregard for rules during early childhood and identify prenatal and postnatal predictors for a high trajectory. Methods: Participants were involved in a longitudinal study of a birth cohort followed yearly from 5 to 74 months of age ( N = 1,942). Prenatal and postnatal predictors were measured by parental report at the beginning of the study, and parents reported child disregard for rules at five time points from 29 to 74 months of age. Results: Four groups of children followed distinct and stable trajectories of mother-rated disregard for rules: Very Low (approximately 9.1%), Low (56.9%), Moderate (29.7%) and Chronic (4.3%). As expected, male sex was a significant predictor of the chronic trajectory (OR = 1.76, CI = 1.09–2.83). Mothers’ history of antisocial behavior (OR = 1.72, CI = 1.02–2.91), and postnatal depressive symptoms experienced by the mother (OR = 1.71, CI = 1.03–2.84) and the father (OR = 2.02, CI = 1.10–3.71) were also important independent predictors. However, contrary to expectations, children’s difficult temperament and parenting at 5 months did not predict chronic disregard for rules beyond other risk factors. Conclusions: High disregard for rules is fairly stable during early childhood and is associated with risk factors identifiable before and shortly after birth which may be used for targeted prevention. [ABSTRACT FROM AUTHOR]

Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS). Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically high DAS. Method: Group-based developmental trajectories of DAS conditional on risk factors were estimated from annual maternal ratings (1½ to 5 years) in a large population sample ( n = 1759). Results: DAS increased substantially in two of the three distinct trajectory groups identified: High-Rising (14.7%); Moderate-Rising (55.4%); and Low (29.9%). Two factors distinguished the High-Rising group from the other two: Difficult temperament at 5 months (High-Rising vs Moderate-Rising: OR = 1.32; 95% CI = 1.13–1.55; High-Rising vs Low: OR = 1.31, CI = 1.12–1.54) and maternal lifetime major depression (High-Rising vs Moderate-Rising: OR = 1.10; CI = 1.01–1.20; High-Rising vs Low: OR = 1.19; CI = 1.08–1.31). Two factors distinguished the High-Rising group from the Low group: High family dysfunction (OR = 1.24; CI = 1.03–1.5) and Low parental self-efficacy (OR = .71; CI = .54–.94). Conclusions: DAS tend to increase in frequency over the first 5 years of life. Atypically high level can be predicted from mother and child characteristics present before 6 months of age. Preventive interventions should be experimented with at risk infants and parents. [ABSTRACT FROM AUTHOR]

Abstract: The study investigated the genetic and environmental contributions to individual differences in measures of socioemotional reactivity and emotion regulation with a sample of 115 monozygotic (MZ) and 156 dizygotic (DZ) 5-month-old twin pairs. Twins’ zygosity was determined by a combination of DNA typing and physical similarity. Twins’ behaviors (motor activity level, social gaze, gaze aversion, positive expression, negative expression, and self-comfort) were videotaped in a laboratory while infants were presented televised sequences of neutral and happy emotional expressions posed by their mother (familiar condition) and a female stranger (unfamiliar condition). Regardless of the social context, the findings based on model-fitting analyses indicated that nonshared environmental influences explained most of the variance of behavioral data. However, there was evidence that motor activity level (an index of emotional arousal) and the latency and frequency of gaze aversion (an index of emotional regulation) were best represented by a model incorporating both additive genetic and nonshared environmental (i.e., AE) influences when infants were exposed to the unfamiliar adult (heritability estimates ranging from 19% to 31%). The results suggest the importance of nonshared environmental influences during early infancy and stress the role of social context for revealing moderate genetic contributions to individual differences in emotional arousal and emotion regulation. [Copyright &y& Elsevier]

The objectives of this study were to establish the different developmental trajectories of hyperactive-impulsive behaviors on the basis of both mother and father ratings at 19, 32, 50, and 63 months, and to examine the predictive validity of these trajectories with respect to later hyperactive-impulsive behaviors, as rated by teachers in the first 2 years of school. Hyperactive-impulsive behaviors were assessed in a population-based sample of 1,112 twins (565 boys and 547 girls) at 19, 32, 50, and 63 months of age. The results revealed a differentiated and consistent view of developmental trajectories of hyperactive-impulsive behaviors derived from these repeated assessments, with 7.1% of children seen by mothers (7% for fathers) as displaying high and stable hyperactive-impulsive behaviors. According to mother ratings, children on a high-chronic trajectory were more likely than other children to display hyperactive-impulsive behaviors at 72 and 84 months according to their teachers. Repeated measures over time and father-based trajectories significantly added to the prediction teacher later ratings of hyperactive-impulsive behaviors. These results support the predictive validity of parental assessment of hyperactive-impulsive behaviors during the preschool years and their use to identify children at risk for further evaluation and possible intervention. [ABSTRACT FROM AUTHOR]

Although peer victimization places children at serious risk for aggressive behavior, not all victimized children are aggressive. The diathesis–stress hypothesis of disease proposes that an environmental stressor such as peer victimization should to lead to maladjustment mostly in those individuals with preexisting genetic vulnerabilities. Accordingly, this study examined whether the link between peer victimization and child aggression is moderated by children's genetic risk for such behavior. Using a sample of 506 6-year-old twins, peer victimization was assessed through peer nominations and aggressive behavior was assessed through peer and teacher reports. Children's genetic risk for aggression was estimated as a function of their co-twin's aggression and the pair's zygosity. Genetic modeling showed that peer victimization is an environmentally driven variable that is unrelated to children's genetic disposition. Results also provided support for the notion of a gene–environment interaction between peer victimization and child's genetic risk for aggressive behavior, albeit only in girls. For boys, peer victimization was related to aggression regardless of the child's genetic risk for such behavior. Different socialization experiences in girls' compared to boys' peer groups may explain the different pattern of results for girls and boys. [ABSTRACT FROM PUBLISHER]

Based on a sample of 406 seven-year-old twins, this study examined whether exposure to friends’ social or physical aggression, respectively, moderates the effect of heritability on children’s own social and physical aggression. Univariate analyses showed that children’s own social and physical aggression were significantly explained by genetic factors, whereas friends’ social and physical aggression represented “true” environmental factors that were unrelated to children’s genetic dispositions. Multivariate analyses further suggested a possible gene–environment interaction in the link between friends’ and children’s physical aggression but not in the link between friends’ and children’s social aggression. Instead, friends’ social aggression was directly related to children’s social aggression, in addition to genetic effects on this behavior. Theoretical and practical implications of these results are discussed. [ABSTRACT FROM AUTHOR]

Using a genetic design of 840 60-month-old twins, this study investigated the genetic and environmental contributions to (a) individual differences in four components of cognitive school readiness, (b) the general ability underlying these four components, and (c) the predictive association between school readiness and school achievement. Results revealed that the contribution of the shared environment for cognitive school readiness was substantial. Genetic effects were more important for the core abilities underlying school readiness than for each specific skill, although shared environment remained the largest factor overall. Genetic, shared, and nonshared environmental factors all accounted for the predictive association between school readiness and early school achievement. These results contribute to a better understanding of the early determinants of school readiness. [ABSTRACT FROM AUTHOR]

Abstract: Children''s negative characteristics are thought to be a factor in evoking hostile parenting responses. This can result in genotype/environment correlations (rGE) in which children''s heritable traits influence the parenting they experience. We did genetic analyses on 292 mothers’ self-reported hostile-reactive behaviors toward each of their twins at 5, 18 and 30 months. Finding heritability for a parenting behavior analyzed as a child phenotype is evidence of rGE correlation. The heritability of maternal behavior was modest (29% at 5 months, 0% at 18 months, and 25% at 30 months) and longitudinal analyses indicated that genetic factors at 5 and 30 months were uncorrelated. Common environment factors, probably reflecting characteristics of the mothers, were the main source of variance at the three ages and were highly correlated through time. We concluded that children''s heritable characteristics evoked maternal negative response at specific times, but were not responsible for the stability of maternal hostility from infancy to toddlerhood. [Copyright &y& Elsevier]

Objective: To examine whether kindergarten children's genetic liability to physically aggress moderates the contribution of friends' aggression to their aggressive behaviors.Method: Teacher and peer reports of aggression were available for 359 6-year-old twin pairs (145 MZ, 212 DZ) as well as teacher and peer reports of aggression of the two best friends of each twin. Children's genetic risk for aggression was based on their cotwin's aggression status and the pair's zygosity.Results: Children's aggression was highly heritable. Unique environment accounted for most of the variance in friends' aggression, although there was also a small genetic contribution (15%). Both genetic liability to aggression and having aggressive friends predicted twins' aggression. However, the contribution of aggressive friends to children's aggression was strongest among genetically vulnerable children. This result was similar for boys and girls, despite sex differences in both aggression and the level of aggression of friends.Conclusions: Affiliation with aggressive friends at school entry is a significant environmental risk factor for aggression, especially for children genetically at risk for aggressive behaviors. Developmental models of aggression need to take into account both genetic liability and environmental factors in multiple settings, such as the peer context, to more precisely describe and understand the various developmental pathways to aggression. The implications for early prevention programs are discussed. [ABSTRACT FROM AUTHOR]

A defective intestinal epithelial tight junction (TJ) barrier has been proposed as an important pathogenic factor contributing to the intestinal inflammation of Crohn's disease. Glucocorticoids are first-line therapeutic agents for the treatment of moderate to severe Crohn's disease. Glucocorticoid treatment has been shown to induce retightening of the intestinal TJ barrier defect in Crohn's disease patients. However, the mechanisms that mediate the glucocorticoid therapeutic action on intestinal TJ barrier function remain unknown. The aim of this study was to elucidate the mechanism of glucocorticoid modulation of the intestinal epithelial TJ barrier using an in vitro model system. Filter-grown Caco-2 intestinal epithelial cells were used as an in vitro model to examine the effects of glucocorticoids on basal intestinal epithelial TJ barrier function and on TNF-α-induced disruption of the TJ barrier. Glucocorticoids (prednisolone and dexamethasone) did not have a significant effect on baseline Caco-2 TJ barrier function but prevented the TNF-α-induced increase in Caco-2 TJ permeability. The glucocorticoid protective effect against the TNF-α-induced increase in Caco-2 TJ permeability required activation of the glucocorticoid receptor (GR) complex. The activation of the GR complex resulted in GR complex binding to the glucocorticoid response element (GRE) site on DNA and activation of a GR-responsive promoter. Glucocorticoids inhibited the TNF-α-induced increase in myosin light chain kinase (MLCK) protein expression, a key process mediating the TNF-α increase in intestinal TJ permeability. The glucocorticoid inhibition of the TNF-α-induced increase in MLCK protein expression was due to the binding of the GR complex to a GRE binding site on the MLCK promoter region suppressing the TNF-α-induced activation. Glucocorticoids inhibit the TNF-α-induced increase in Caco-2 TJ permeability. The prednisolone protective action was mediated by binding of activated GR complex to the GRE site on the MLCK promoter, suppressing the TNF-α-induced increase in MLCK gene activity, protein expression, and subsequent opening of the intestinal TJ barrier. [ABSTRACT FROM AUTHOR]

This study compared the contribution of genes and environment to teacher-rated reactive and proactive aggression in 6-year-old twin pairs (172 pairs: 55 monozygotic girls, 48 monozygotic boys, 33 dizygotic girls, 36 dizygotic boys). Genetic effects accounted for 39% of the variance of reactive aggression and for 41% of the variance of proactive aggression. The remainder of the variance was explained by unique environmental effects. Genetic as well as unique environmental effects were significantly correlated across reactive and proactive aggression (genetic correlation = .87, environmental correlation = .34), but this overlap was largely due to a common underlying form of aggression (i.e., teacher-rated physical aggression). Once common etiological factors due to physical aggression were accounted for, reactive and proactive aggression shared no other genes and only a few environmental influences, although additional specific genetic and environmental effects were observed for both reactive and proactive aggression. These specific effects indicate that both reactive and proactive aggression may be influenced mostly by socialization experiences that are specific to each type of aggression and only to a very small degree by specific genes. [ABSTRACT FROM AUTHOR]

Given the importance of parenting for the child's early socio-emotional development, parenting perceptions and behaviours, and their correlates, should be assessed as early as possible in the child's life. The goals of the present study were 1) to confirm, in two parallel population-based samples, including a large sample of twins, the factor structure of a new self-administered questionnaire assessing both parents’ specific parenting perceptions and behaviours toward their 5-month-old infants (i.e., parental self-efficacy, perceived parental impact, parental hostile-reactive behaviours and parental overprotection), 2) to identify the specific risk factors associated with the negative side of these parenting dimensions, 3) to document the genetic-environmental etiology of these parenting dimensions through the twin method.Parents (2,122 mothers and 1,829 fathers) of 5-month-old infants, and parents of 5-month-old infant twins (510 families) completed the questionnaire (28 items). The data were submitted to a series of confirmatory factor analyses. The contribution to parenting of a variety of risk factors was examined in the two samples using regression analyses. A series of quantitative genetic analyses were performed to quantify the different sources of variation in parenting.A consistent factor structure was found across informants and across samples. There were significant mean differences in parenting between mothers and fathers, as well as between parents of twins and parents of singletons. A differentiated pattern of association with risk factors was found for each dimension of parenting. The twin analyses revealed that shared environment accounted for each parenting dimension. Maternal hostile-reactive behaviours were also moderately related to genetic factors in the child and this association was mainly mediated by the infant difficultness.The overall pattern of results was consistent withview of parenting as multiply determined. The longitudinal follow-up of these families should provide the means for testing developmental models about the determinants and outcomes of these parenting dimensions. [ABSTRACT FROM AUTHOR]

TNF-α plays a central role in the intestinal inflammation of various inflammatory disorders including Cohn's disease (CD). TNF-α-induced increase in intestinal epithelial tight junction (TJ) permeability has been proposed as one of the proinflammatory mechanisms contributing to the intestinal inflammation. The intracellular mechanisms involved in the TNF-α-induced increase in intestinal TJ permeability remain unclear. The purpose of this study was to investigate the possibility that the TNF-α-induced increase in intestinal epithelial TJ permeability was regulated by myosin light-chain kinase (MLCK) protein expression, using an in vitro intestinal epithelial model system consisting of the filter-grown Caco-2 intestinal epithelial monolayers. TNF-α (10 ng/ml) produced a time-dependent increase in Caco-2 MLCK expression. The TNF-α increase in MLCK protein expression paralleled the increase in Caco-2 TJ permeability, and the inhibition of the TNF-αinduced MLCK expression (by cycloheximide) prevented the increase in Caco-2 TJ permeability, suggesting that MLCK expression may be required for the increase in Caco-2 TJ permeability. The TNF-α increase in MLCK protein expression was preceded by an increase in MLCK mRNA expression but not an alteration in MLCK protein degradation. Actinomycin-D prevented the TNF-α increase in MLCK mRNA expression and the subsequent increase in MLCK protein expression and Caco-2 TJ permeability, suggesting that the increase in MLCK mRNA transcription led to the increase in MLCK expression. The TNF-α increase in MLCK protein expression was also associated with an increase in Caco-2 MLCK activity. The cycloheximide inhibition of MLCK protein expression prevented the TNF-α increase in MLCK activity and Caco-2 TJ permeability. Moreover, inhibitors of MLCK, Mg2+-myosin ATPase, and metabolic energy prevented the TNF-α increase in Caco-2 TJ permeability, suggesting that the increase in MLCK activity was required for the TNF-α-induced opening of the Caco-2 TJ barrier. In conclusion, our results indicate for the first time that 1) the TNF-α increase in Caco-2 TJ permeability was mediated by an increase in MLCK protein expression, 2) the increase in MLCK protein expression was regulated by an increase in MLCK mRNA transcription, and 3) the increase in Caco-2 TJ permeability required MLCK protein expression-dependent increase in MLCK activity. [ABSTRACT FROM AUTHOR]

This study examined the changes in children's social network and specific self-perceptions during the transition from elementary school to junior high school (JHS). The participants were 200 preadolescent children (104 girls, 96 boys). Children's self-perceptions (global self-worth, perceived academic competence, and perceived social acceptance) and social network characteristics (parents and peer-enacted support) were evaluated four consecutive times over a 2-year period. Despite a slight decrease in the size of children's social network after the transition, the passage into JHS had no negative impact on the quality and functional aspects of their relationships with parents and school friends. The school transition was instead associated with an intensification of supportive relationships with school friends. Children's perceived social acceptance also increased suddenly after the JHS transition, while children's perceived scholastic competence decreased simultaneously during that time. Children's general self-esteem was then observed to decline progressively over a longer period of time. [ABSTRACT FROM AUTHOR]

In the prevention of physical aggression, possible etiological links with language development are rarely taken into account. Indeed, little is known about when language and aggressive behavior become linked during development and which mechanisms are responsible for this association. This study investigated the association between physical aggression and language in late infancy with a genetic design that involved 562 19-month-old twins. A modest but significant correlation (r = -.20) was found between physical aggression and expressive vocabulary. Substantial heritability was found for physical aggression. Quantitative genetic modeling suggests that the correlation between expressive vocabulary and physical aggression cannot be explained by shared etiologies. However, phenotype-to-phenotype models indicate that the covariation can be entirely accounted for by a significant phenotypic path from expressive vocabulary to physical aggression. The implications of these results for early prevention of chronic physical aggression are discussed. [ABSTRACT FROM AUTHOR]

This study tests theoretical and developmental models of the causal ordering between academic selfconcept and academic achievement in a multicohort-multioccasion design (i.e., 3 age cohorts, each with 3 measurement waves). Participants were students in Grades 2, 3, and 4 from 10 elementary schools. The structural equation model for the total sample supported a reciprocal-effects model, indicating that achievement has an effect on self-concept (skill-development model) and that academic self-concept has an effect on achievement (self-enhancement model). This pattern was replicated in tests of invariance across the 3 age cohorts and did not support the developmental hypothesis that skill-development and self-enhancement models would vary with age. Discussion centers on the theoretical, methodological, and practical implications of the results. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate whether a dose-response curve exists for erythromycin, determine the lowest effective dose of erythromycin needed to improve gastric motility, and compare erythromycin's effectiveness with that of metoclopramide in improving gastric emptying. Design: Randomized, crossover, multiintervention trial. Setting: Inpatient clinical research center. Subjects: Ten healthy volunteers (four men, six women) from the general population. Intervention: On each study day, the subjects were infused with erythromycin 0.75 mg/kg, 1.5 mg/kg, or 3.0 mg/kg; metoclopramide 10 mg; or placebo, in random order. Subjects then drank Ensure 200 ml mixed with acetaminophen 1.5 g. Gastric emptying was estimated by comparing the area under the curve after 60 minutes for acetaminophen absorption using four limed blood draws. Measurements and Main Results: Erythromycin increased gastric emptying in a dose-response manner. Erythromycin 3.0 mg/kg and metoclopramide 10 mg were associated with statistically significant increases in liquid gastric emptying compared with placebo. During infusion, nausea and stomach cramping were associated with the 3.0-mg/kg dose of erythromycin; drowsiness was associated with metoclopramide. Conclusion: In patients requiring intravenous erythromycin for gastric motility, the 3.0-mg/kg dose seems the most effective, with a reasonable side effect profile. [ABSTRACT FROM AUTHOR]

We examined whether adolescents' loneliness and social withdrawal mediated the association between maternal depressive symptoms and adolescent suicidality. Secondary analyses on the Québec Longitudinal Study of Child Development data were conducted (n = 1,623). Each mother completed the Centre for Epidemiologic Studies Depression Scale (at child ages 5 months, 1.5, 3.5, 5, and 7 years). Adolescent's social withdrawal (adolescent, father, and teacher reported at 10, 12, and 13 years) and loneliness (adolescent reported at 10, 12, and 13 years), were assessed using items from the Social Behavior Questionnaire and the Loneliness and Social Satisfaction Questionnaire, respectively. Adolescents completed self-reports to assess suicidal thoughts and attempts at 13, 15, 17, and 20 years. Children of mothers with higher levels of maternal depressive symptoms had an increased risk for suicidality (OR = 1.15, 95% CI: 1.03–1.28). Loneliness explained 16% of the total effect of maternal depressive symptoms on adolescent suicidality (indirect effect OR = 1.02, 95% CI: 1.00–1.04). There was no indirect effect of maternal depressive symptoms on adolescent suicidal outcomes via social withdrawal (indirect effect OR = 1.00, 95% CI: 0.99–1.02). Interventions that target loneliness may be beneficial for decreasing the risk for suicidality among adolescents of mothers with depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Hyperactivity and inattention, the symptoms of ADHD, are marked by high levels of heritability and intergenerational transmission. Two distinct pathways of genetic intergenerational transmission are distinguished: direct genetic transmission when parental genetic variants are passed to the child's genome and genetic nurture when the parental genetic background contributes to the child's outcomes through rearing environment. This study assessed genetic contributions to hyperactivity and inattention in childhood through these transmission pathways. Methods: The sample included 415 families from the Quebec Newborn Twin Study. Twins' hyperactivity and inattention were assessed in early childhood by parents and in primary school by teachers. The polygenic scores for ADHD (ADHD‐PGS) and educational attainment (EA‐PGS) were computed from twins' and parents' genotypes. A model of intergenerational transmission was developed to estimate (1) the contributions of parents' and children's PGS to the twins' ADHD symptoms and (2) whether these variances were explained by genetic transmission and/or genetic nurture. Results: ADHD‐PGS explained up to 1.6% of the variance of hyperactivity and inattention in early childhood and primary school. EA‐PGS predicted ADHD symptoms at both ages, explaining up to 1.6% of the variance in early childhood and up to 5.5% in primary school. Genetic transmission was the only significant transmission pathway of both PGS. The genetic nurture channeled through EA‐PGS explained up to 3.2% of the variance of inattention in primary school but this association was non‐significant. Conclusions: Genetic propensities to ADHD and education predicted ADHD symptoms in childhood, especially in primary school. Its intergenerational transmission was driven primarily by genetic variants passed to the child, rather than by environmentally mediated parental genetic effects. The model developed in this study can be leveraged in future research to investigate genetic transmission and genetic nurture while accounting for parental assortative mating. [ABSTRACT FROM AUTHOR]

We investigated whether child temperament (negative emotionality, 5 months) moderated the association between maternal stimulation (5 months–2½ years) and academic readiness and achievement (vocabulary, mathematics, and reading). We applied structural equation modeling to the data from the Quebec Longitudinal Study of Child Development (N = 1121–1448; mostly Whites; 47% girls). Compared to children with low negative emotionality, those with high negative emotionality had higher levels of academic readiness (6 years) and mathematics achievement (7 years) when exposed to high levels of maternal stimulation (β = 3.17, p <.01 and β = 2.91, p <.01, respectively). The results support the differential susceptibility model whereby highly emotionally negative children were more susceptible to the influences of low and high levels of maternal stimulation in academic readiness and mathematics achievement's developments. [ABSTRACT FROM AUTHOR]