This Career Development Award (K01) will provide the candidate with the necessary skills to develop an independent research program focused on using population-based data to identify the psychological, physiological, and environmental mechanisms underlying the association between childhood adversity and the later onset of mood and anxiety disorders and to examine the role of genetic factors in altering developmental trajectories among children exposed to adversity. Although adverse childhood experiences, such as maltreatment and exposure to family violence, account for a substantial proportion of mental disorders in the population, the complex developmental pathways that underlie these associations remain poorly characterized. The overall aim of the current application is to test a developmental epidemiologic model that posits a central role of emotional and physiological reactivity as a mechanism linking childhood adversity to the subsequent onset of mood and anxiety disorders. The model predicts that childhood adversity is more likely to trigger heightened emotional reactivity among individuals with specific genetic polymorphisms that increase vulnerability to stress. The training plan is designed to provide the candidate with skills in developmental psychopathology, stress biology and psychophysiology, and genetic epidemiology. Specifically, the candidate will acquire the knowledge and skills to: a) conduct developmentally informed studies to identify psychological and physiological mechanisms linking childhood adversity to mood and anxiety disorders;b) design, conduct, and analyze genetically informative studies;c) identify biologically plausible phenotypes that link genotype, childhood adversity, and mood and anxiety disorders;and d) conduct prospective epidemiologic studies of individuals exposed to childhood adversities, which assess both genetic and environmental risk factors. These skills will be developed through a combination of didactic training, guided readings, and mentored research projects. The proposed research program involves a combination of original data collection and analysis of existing epidemiologic data. The candidate will collect psychopathology, psychophysiology, experience sampling, and genetic data from a community sample of adolescents to examine the central hypotheses of the conceptual model. Psychophysiology methods and a candidate gene approach will be used to define a potential phenotype involving heightened emotional and physiological reactivity that links genetic vulnerability, childhood adversity exposure, and mood and anxiety disorders. The conceptual model also will be tested through analysis of three longitudinal epidemiologic data sets: the National Comorbidity Survey II, the Avon Longitudinal Study of Children and Parents, and the Nurses'Health Study II, two of which measure both genetic and environmental risk factors. Training activities and results will be used to develop an R01 application for a prospective epidemiologic study that assesses both genetic and environmental risk factors and aims to identify developmental pathways linking childhood adversity to the onset of mood and anxiety disorders.

Public Health Relevance

The proposed research aims to identify psychological and physiological mechanisms underlying the association between childhood adversity and the later onset of mood and anxiety disorders and to determine whether genetic polymorphisms associated with the stress response system modify developmental trajectories among individuals exposed to childhood adversity, including maltreatment and family violence. Elucidation of these mechanisms, and the role of genetic vulnerability in altering mediating pathways, is critical to inform the development of preventive interventions targeting children exposed to adversity. Given that a substantial proportion of mental disorders in the population are directly attributable to childhood adversity, the development of such interventions represents an important public health priority.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH092526-02
Application #
8212078
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Anderson, Kathleen C
Project Start
2011-02-01
Project End
2015-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2012
Total Cost
$179,804
Indirect Cost
$13,319
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Carliner, Hannah; Keyes, Katherine M; McLaughlin, Katie A et al. (2016) Childhood Trauma and Illicit Drug Use in Adolescence: A Population-Based National Comorbidity Survey Replication-Adolescent Supplement Study. J Am Acad Child Adolesc Psychiatry 55:701-8
McLaughlin, Katie A (2016) Future Directions in Childhood Adversity and Youth Psychopathology. J Clin Child Adolesc Psychol 45:361-82
Gold, Andrea L; Sheridan, Margaret A; Peverill, Matthew et al. (2016) Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing. J Child Psychol Psychiatry 57:1154-64
Benjet, C; Bromet, E; Karam, E G et al. (2016) The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychol Med 46:327-43
McLaughlin, Katie A; Sheridan, Margaret A; Gold, Andrea L et al. (2016) Maltreatment Exposure, Brain Structure, and Fear Conditioning in Children and Adolescents. Neuropsychopharmacology 41:1956-64
Busso, Daniel S; McLaughlin, Katie A; Sheridan, Margaret A (2016) Dimensions of Adversity, Physiological Reactivity, and Externalizing Psychopathology in Adolescence: Deprivation and Threat. Psychosom Med :
Dennison, Meg J; Sheridan, Margaret A; Busso, Daniel S et al. (2016) Neurobehavioral markers of resilience to depression amongst adolescents exposed to child abuse. J Abnorm Psychol 125:1201-1212
Gooding, Holly C; Milliren, Carly E; Austin, S Bryn et al. (2016) Child Abuse, Resting Blood Pressure, and Blood Pressure Reactivity to Psychosocial Stress. J Pediatr Psychol 41:5-14
Tibu, F; Sheridan, M A; McLaughlin, K A et al. (2016) Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder. Psychol Med 46:529-41
Peverill, Matthew; McLaughlin, Katie A; Finn, Amy S et al. (2016) Working memory filtering continues to develop into late adolescence. Dev Cogn Neurosci 18:78-88

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