Laura A. Baker - US grants

Human aggression and antisocial behavior are known to be the product of both social and biological risk factors. What is not yet understood is how environment and genetic factors may mediate the interrelationships among these risk factors and antisocial outcomes. A study of twins and their families would provide the ideal opportunity to answer the critical question in this regard: Do measured social and biological variables relate to antisocial development for environment or genetic reasons? Our ability to develop effective and efficient interventions for antisocial behavior rest heavily upon the answer to this question. A study of normal variation in antisocial and aggressive behavior is proposed for 600 twin pairs (both male and female), aged 9-10 years old during an initial assessment, and aged 11-12 years old during a follow-up assessment. The study will provide the first opportunity to investigate the environmental and genetic underpinnings of important social and biological risk factors for unlawful, antisocial and aggressive behavior in boys and girls on the risk of adolescence. Social risk factors will include aspects of the family environment, such as socio-economic status, emotional climate, cohesion, parental warmth and affection, parental supervision, discipline and control. Specific environmental factors for each twin will also be studied including individual relationships with each family member, as well as peer-group characteristics. Biological risk factors will include psychophysiological indicators of arousal (both electrodermal and cardiac channels), as well as neuropsychological and cognitive testing. Both the social and biological risk factors studied here have previously been shown to distinguish between children at high and low risk for aggressive and antisocial behavior. The twin design allows the unique occasion to estimate the relative contributions of environmental and genetic factors to both antisocial behavior and their risk factors, as well as their interrelationships. Of particular importance are whether the links between antisocial behavior with biological and social risk factors, if they exist in this sample, are mediated by genetic or environmental factors. DNA samples will be extracted through mouthwash procedures and will serve two purposes. First, zygosity determination will be made using PCR tests for the 400 same-sex pairs. Then, the remaining DNA will be stored for future analyses of specific genetic loci hypothesized to show associations with antisocial behaviors. We anticipate that by the end of this project, a substantial number of candidate genes will be suggested for antisocial outcomes. At that point, additional funding will be sought to confirm these associations using the rich data source resulting from this project. Detailed knowledge of the underlying biological and genetic mechanisms in aggressive and other forms of antisocial behavior will lead to a greater understanding of how social variables in turn are related to antisocial outcomes, ultimately enabling greater control of this important social phenomenon.

DESCRIPTION (provided by applicant): We have implemented a major longitudinal twin study of aggression and antisocial behavior (ASB) and its social and biological risk factors (#MH58354). Based on two waves of data collected at ages 9-10 (Wave 1) and 11-12 (Wave 2), we study genetic and environmental variations in childhood conduct problems, and how these vary across gender, rater, and definition of ASB. Relationships of ASB with known risk factors (social and biological) have been confirmed, and new relationships have been identified. The extent to which risk factor/ASB relationships are mediated by environmental and/or genetic factors is studied and is of key importance to future intervention. We propose to extend the study to include 2 additional waves of assessment at ages 14-15 (Wave 3) and 16-17 (Wave 4), to obtain comprehensive measures of antisocial and aggressive behavior and their risk factors for these same children during adolescence. The primary aim of the next phase is to understand environmental, genetic, and phenotypic continuities in ASB and its biological and social risk factors from age 9-17. The first 5-year phase provided comprehensive assessments of behavioral, neurocognitive, social, and psychophysiological function during two waves of investigation. In Wave 1, twins and their primary caregivers participated in the most extensive assessment, including structured interviews about behavior and psychosocial risk factors, neurocognitive testing, and psychophysiological responses (cardiovascular, electrodermal, electrocortical, and electromyographic) during rest periods and a variety of tasks (attention and emotion-related). A follow-up assessment in Wave 2 focused primarily on children's'behavior and social risk factors (peer and family characteristics), with a limited psychophysiological recording (autonomic measures only). Adding two more waves of data collection during adolescence will provide the most comprehensive, prospective longitudinal data on ASB ever obtained in a genetically informative design. This four-wave, 10 year longitudinal twin study will provide the unique opportunity to understand how genes and environment combine and interact to produce antisocial outcomes in children and adolescents. In this revised application, clarifications of theoretical framework and a detailed plan for analyses are provided. The data analysis core staff has been expanded to assist in the complex phenotypic and genetic analyses that will ensue from this rich and unique longitudinal dataset.

DESCRIPTION (provided by applicant): The present study is a continuation into adulthood of a major longitudinal twin study of aggression and antisocial behavior (ASB) and its social and biological risk factors (#MH58354) in a diverse urban sample. The first two funding periods provided comprehensive laboratory assessments of behavioral, neurocognitive, social and psychophysiological function, and multi-trait, multi-rater assessments of externalizing psychopathology during four waves of investigation when the twins were ages 9-10 (Wave 1) 11-13 (Wave 2), 14-16 (Wave 3) and 17-18 years old (Wave 4). Relationships of ASB with known risk factors (social and biological) were confirmed, and new relationships identified. The extent to which genetic and environmental factors affect ASB, its risk factors and their relationships has also been elucidated, with many findings shown to vary across gender, informant, definition of ASB, and age. We propose to extend the study to include an adult assessment at ages 19-23 (Wave 5), to obtain comprehensive measures of antisocial and aggressive behavior and their risk factors during a period of greatest risk for criminal offending, antisocial personality disorder and substance abuse. The primary aim of the next phase is to understand environmental, genetic, and phenotypic continuities in externalizing behavior problems and their biological and social risk factors through adulthood, including the prediction of adult outcomes from childhood and adolescent measures. Adding the adult assessment will yield the most comprehensive, prospective longitudinal data on externalizing behavior problems ever obtained in a genetically informative design. This five-wave, 15 year longitudinal twin study will provide the unique opportunity to understand how genes and environment combine and interact to produce antisocial outcomes from childhood to adulthood, and will greatly enhance our understanding of externalizing psychopathology and its heterogeneous developmental trajectories. Understanding gene-environment interplay in the development of externalizing psychopathology is of key importance to future intervention and prevention. PUBLIC HEALTH RELEVANCE: Continuation of this longitudinal twin study into adulthood will provide the unique opportunity to unravel the developmental course of externalizing behavior problems across several critical periods of the lifespan, including childhood, adolescence, and ultimately young adulthood. Understanding the development of externalizing problems and their underlying mechanisms will enable prediction of adult psychopathology from early childhood, and provide opportunities to identify protective factors and thus effective prevention of seriously deviant and maladaptive behavior during adulthood. Given the costs of antisocial behavior-including criminal offending, substance use, and psychopathy--to both individuals and society, the reduction of these behaviors will provide enormous benefits to public health.)

DESCRIPTION (provided by applicant): The growing population of children in American cities is exposed to various neurotoxins present in urban environments which may damage their developing brains. Over the last decade, environmental health scientists have generated compelling data on neurotoxicity in animals and humans exposed to present-day air pollutants from road traffic emissions (or traffic air pollution [TAP]), including particulate matter and ozon in urban environments. Experimental animal models have demonstrated that early life exposures to these urban air pollutants result in memory impairment and long-term neurobehavioral changes. Consistent with neurotoxicological literature, previous data from both cross-sectional and longitudinal epidemiologic studies showed a wide range of adverse neurocognitive effects (including low IQ) associated with TAP exposure in school-aged or younger children. However, it remains unclear whether TAP-mediated adverse neurocognitive effects persist into later life possibly affecting academic performance and educational attainment in adolescents and young adults. Although toxicologists have revealed clear evidence of air pollution-induced neurotoxicity in the prefrontal lobe and hippocampus, epidemiologic studies have not yet examined higher cortical control functions (e.g., executive functions [EFs]; emotion regulation) as neuropsychological mediators of the adverse exposure-effects on neurodevelopment. Previous studies only provided very little insight on the likelihood of joint adversities resulting from exposures to both neurotoxic TAP and social stressors commonly experienced by urban-dwelling children. To address these knowledge gaps, the primary objectives of this application are to: (1) generate preliminary data and infrastructure needed for a planned long-term study on neurodevelopment in urban environments; and (2) develop a conceptual framework to elucidate neuropsychological pathways contributing to impaired cognition and long-term socioeconomic consequences of exposures to urban air pollutants. Specifically, we propose a longitudinal study built on an ongoing (2000- onwards) and well-characterized urban-dwelling Southern California Twin Cohort (R01MH058354) with comprehensive data on neuropsychological functions and outcomes assessed from school-age (aged 9-10) to young adults (aged 19-23). This application leverages the unique, prospectively-collected environmental data and resources of the ongoing Children's Health Study, enabling the estimation of early life (1990-onward) exposure to air pollution and detailed characterization of intra-urban TAP exposure during adolescents. Drawing from two theoretical models (cognitive vulnerability-stress response and emotional dysregulation) in mental health research, we will test the hypothesis that EFs/emotion regulation and their developmental trajectories serve as both the central target and neuropsychological mediators of subsequent adverse effects of TAP exposure on cognitive abilities and socioeconomic attainment. The successful performance of this project may greatly advance the emerging field of developmental neurosciences in urban environments.