Sandra A. Wiebe, Ph.D. - US grants

DESCRIPTION (provided by applicant): One central tenet of "personalized medicine" is to be able to predict who is at risk for later medical conditions, including mental illness (NIH, 2007). To transform our knowledge of the origins, mechanisms, and processes that contribute to later dysfunction, the National Advisory Mental Health Council (2007) has called for increased longitudinal, "trajectory-based" studies that include "sensitive, malleable periods of neurodevelopment" to meet Objectives 1 and 2 of the new NIMH Strategic Plan. With recent methodological advances that have shed light on developmental pathways toward childhood psychopathology, there is a pressing need reflected in PA07-158 to identify specific precursors to improve early identification and intervention. Executive control (EC) is a strong candidate precursor for childhood externalizing disorders (including ADHD), although two challenges have hampered progress: 1) lack of a precise definition of EC and 2) inadequate understanding of how EC contributes to later functional outcomes. In this past funding period, we have made substantial progress in defining EC in preschool children by using sophisticated statistical methods to empirically determine the best fitting, theoretically derived model. The objective of this renewal application, then, is to elucidate how precursor EC relates to later functional outcome, the next translational step towards clinical application. Participants will be the large, carefully, longitudinally (every 9 months, 3-0 to 5-3 years) sampled preschool cohort (half are at sociodemographic risk) who will enter grades 1 or 2 in fall 2009-2011. Multi-method assessments of functional outcome in spring grades 1-4 will be conducted, focusing on externalizing problems (impulsivity/hyperactivity, inattention, defiance, and aggression), social skills (sensitivity, responsibility, and peer relationships), academic skills (mathematics and reading achievement), and mastery problems (poor motivation, persistence, strategy use). The cohort is on the cusp of a key 5->7 shift, the developmental transition characterized by a substantial increase in adult expectations for goal-directed thought, sustained independent work, adaptive relationships and social functioning. In this 5->7 shift, elementary school is the central context where these increased expectations challenge or "press" the child to deploy executive control to successfully manage this transition, a key factor in later functional success. Structural equation modeling will be used to test the a priori direct and meditation relations among preschool executive control, behavior in the 5->7 shift, and functional outcome. To pinpoint who is at greater risk for poor outcome, cutting-edge, person-centered growth mixture modeling will be conducted to identify latent subgroups of preschool children with poor EC development and then to compare later functional outcome and examine the contribution of responsive parenting. Characterizing the nature of executive control in the preschool period and how it relates to trajectories of later functional outcome will elucidate the fundamental mechanisms that go awry in childhood psychopathology and identify precursors for use in future work to tailor preventive interventions to those who stand to benefit most. PUBLIC HEALTH RELEVANCE: Identifying early precursors in pathways to later dysfunction is critical to enhance preventive interventions in the longer term. Executive control plays a fundamental, and perhaps causal, role in externalizing problems and related adverse social and academic outcomes, and therefore is a strong candidate for translational use in early identification. Understanding the longitudinal relations of preschool executive control and functional outcome in grades 1-4, and characterizing putative mechanisms in a large, well-characterized cohort who range in sociodemographic risk, will elucidate important developmental pathways towards psychopathology.

DESCRIPTION (provided by applicant): Prenatal tobacco exposure (PTE) is the most common preventable risk for adverse developmental outcome, affecting more than 500,000 infants per year. PTE has been linked to an increased likelihood of ADHD and other childhood disruptive behavior disorders. Several studies have found externalizing behavior problems in tobacco-exposed (TE) children in early childhood, as young as 2-3 years of age (Day, 2000;Wakschlag, 2006a). Poor self-regulation (encompassing both executive control and emotion regulation) subserved by prefrontal systems likely underlies the development of externalizing behavior problems in childhood (Nigg &Casey, 2006), because PTE disrupts dopaminergic function that drives prefrontal neural systems, providing a link between PTE and externalizing symptomatology. The purpose of this exploratory R21 project is to characterize the impact of PTE on self-regulation and the relation to externalizing problem behaviors to better understand the pathways to later externalizing disorders. Self-regulatory abilities in young TE children will be investigated by following an existing NIDA-funded cohort whose prenatal tobacco exposure has been prospectively quantified and verified biochemically (DA014661). Children will be assessed at age 36 months, a point early in development when reliable and valid measures of executive control and emotion regulation are available (Carlson, 2005, 2007;Espy, in press;Kochanska 2000). To accurately and reliably measure executive control and emotion regulation, sophisticated latent variable models are used, where multiple, child-friendly tasks are selected as indices of each construct, and the common factor variance is determined to generate "purer" latent construct variables that are less influenced by extraneous sources of variability (Miyake, 2000). TE children will demonstrate deficits in self-regulation, compared to non-exposed peers, and a dose- response relation will be observed. Clinically-relevant problem behaviors are assessed with state-of-the-art multi-method tools, the BASC-2 and DB-DOS (Wakschlag, 2005) and will be related to PTE via self-regulatory skills. Possible interactions with parenting and home environment quality will be explored. These relations will be considered controlling for other risk factors, including prenatal alcohol exposure, maternal self-regulation, and postnatal environmental tobacco exposure. The findings from this exploratory R21 project will help to better determine the mechanisms that underlie problem behaviors in young children that will inform efforts to develop targeted preventive interventions and public health campaigns in the longer term. PUBLIC HEALTH RELEVANCE: Prenatal tobacco exposure (PTE) affects more than 500,000 infants per year, and has been linked to increased disruptive behavior in young children (Day, 2000;Wakschlag, 2006a). This project will examine the mechanisms underlying this link by examining self-regulation, or the ability to control behavior and emotions in prenatally tobacco-exposed and non-exposed preschool children. Understanding the specific deficits associated with PTE will drive development of targeted interventions for at-risk preschoolers, and improve public health efforts to assist women smokers to quit during pregnancy.

DESCRIPTION (provided by applicant): Prenatal tobacco exposure (PTE) is the most common preventable risk for adverse developmental outcome, affecting more than 500,000 infants per year. PTE has been linked to an increased likelihood of ADHD and other childhood disruptive behavior disorders. Several studies have found externalizing behavior problems in tobacco-exposed (TE) children in early childhood, as young as 2-3 years of age (Day, 2000;Wakschlag, 2006a). Poor self-regulation (encompassing both executive control and emotion regulation) subserved by prefrontal systems likely underlies the development of externalizing behavior problems in childhood (Nigg &Casey, 2006), because PTE disrupts dopaminergic function that drives prefrontal neural systems, providing a link between PTE and externalizing symptomatology. The purpose of this exploratory R21 project is to characterize the impact of PTE on self-regulation and the relation to externalizing problem behaviors to better understand the pathways to later externalizing disorders. Self-regulatory abilities in young TE children will be investigated by following an existing NIDA-funded cohort whose prenatal tobacco exposure has been prospectively quantified and verified biochemically (DA014661). Children will be assessed at age 36 months, a point early in development when reliable and valid measures of executive control and emotion regulation are available (Carlson, 2005, 2007;Espy, in press;Kochanska 2000). To accurately and reliably measure executive control and emotion regulation, sophisticated latent variable models are used, where multiple, child-friendly tasks are selected as indices of each construct, and the common factor variance is determined to generate "purer" latent construct variables that are less influenced by extraneous sources of variability (Miyake, 2000). TE children will demonstrate deficits in self-regulation, compared to non-exposed peers, and a dose- response relation will be observed. Clinically-relevant problem behaviors are assessed with state-of-the-art multi-method tools, the BASC-2 and DB-DOS (Wakschlag, 2005) and will be related to PTE via self-regulatory skills. Possible interactions with parenting and home environment quality will be explored. These relations will be considered controlling for other risk factors, including prenatal alcohol exposure, maternal self-regulation, and postnatal environmental tobacco exposure. The findings from this exploratory R21 project will help to better determine the mechanisms that underlie problem behaviors in young children that will inform efforts to develop targeted preventive interventions and public health campaigns in the longer term. PUBLIC HEALTH RELEVANCE: Prenatal tobacco exposure (PTE) affects more than 500,000 infants per year, and has been linked to increased disruptive behavior in young children (Day, 2000;Wakschlag, 2006a). This project will examine the mechanisms underlying this link by examining self-regulation, or the ability to control behavior and emotions in prenatally tobacco-exposed and non-exposed preschool children. Understanding the specific deficits associated with PTE will drive development of targeted interventions for at-risk preschoolers, and improve public health efforts to assist women smokers to quit during pregnancy.