This continuing Midcareer Investigator Award in Patient-Oriented Research (K24) application is in response to program announcement (PA-09-037). Early maltreatment and pediatric maltreatment-related PTSD symptoms are associated with dysregulation of biological stress systems, adverse brain maturation, and medial prefrontal cortical dysfunction. Adults with treatment resistant substance use disorders are more likely to have histories of early trauma. Building on previous work in developmental traumatology, the aim of this K24 is to investigate the neurobiology of pathways from trauma to substance abuse. The objectives of the career development plan are to: 1) develop expertise in psychiatric genetics;2) further the candidate's knowledge of diffusion tensor imaging by learning FSL and examining the relationship between early trauma and white matter development as predictors of ventral medial PFC activation to decision making tasks in our Great Smoky Mountains Study (GSMS) subjects;3) increase the candidate's practical and empirical knowledge in the statistical aspects of longitudinal studies;and 4) emphasize knowledge dissemination of the translational components of this research by mentoring junior colleagues in child maltreatment research and its relationship to substance use disorders. The research plan is linked to a recently funded NIDA grant """"""""Prefrontal Function in Adolescent Limited vs. Life Course Persistent SUD,"""""""" a brain imaging study to help elucidate the brain mechanisms of persistence (called life course persistent-LCP-SUD) versus desistence (called adolescence-limited (AL-SUD) of adolescent onset substance use disorder (SUD) into young adulthood as part of the GSMS. Those with LCP-SUD differed in their preadolescent risk factors for SUD and were more likely to have early life stress (ELS) including histories of child maltreatment. Thus this work is a developmental outgrowth of the PI's previous research in the psychobiology of maltreatment. We will examine ELS and genetic factors to test the hypotheses ELS and candidate genetic markers may impair prefrontal cortex (PFC) function increasing the risk for LCP-SUD.

Public Health Relevance

The intergenerational transmission of child maltreatment and substance abuse are important public health problems. In adults, histories of child maltreatment are associated with persistence of substance use disorders. Understanding the effects of early trauma and genetics on white matter development will help us better understand causal mechanisms that may lead to interventions.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Boyce, Cheryl A
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Duke University
Schools of Medicine
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Nooner, Kate B; Hooper, Stephen R; De Bellis, Michael D (2018) An examination of sex differences on neurocognitive functioning and behavior problems in maltreated youth. Psychol Trauma 10:435-443
Stave, Elise A; De Bellis, Michael D; Hooper, Steven R et al. (2017) Dimensions of Attention Associated With the Microstructure of Corona Radiata White Matter. J Child Neurol 32:458-466
Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R et al. (2016) Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder. Neuropsychopharmacology 41:791-801
Urger, Sacide E; De Bellis, Michael D; Hooper, Stephen R et al. (2015) The superior longitudinal fasciculus in typically developing children and adolescents: diffusion tensor imaging and neuropsychological correlates. J Child Neurol 30:9-20
De Bellis, Michael D; Hooper, Stephen R; Chen, Steven D et al. (2015) Posterior structural brain volumes differ in maltreated youth with and without chronic posttraumatic stress disorder. Dev Psychopathol 27:1555-76
Brown, Sandra A; Brumback, Ty; Tomlinson, Kristin et al. (2015) The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA): A Multisite Study of Adolescent Development and Substance Use. J Stud Alcohol Drugs 76:895-908
De Bellis, Michael D; Zisk, Abigail (2014) The biological effects of childhood trauma. Child Adolesc Psychiatr Clin N Am 23:185-222, vii
Hooper, Stephen R; Woolley, Donald; De Bellis, Michael D (2014) Intellectual, neurocognitive, and academic achievement in abstinent adolescents with cannabis use disorder. Psychopharmacology (Berl) 231:1467-77
Li, Wei; Wu, Bing; Batrachenko, Anastasia et al. (2014) Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan. Hum Brain Mapp 35:2698-713
Crozier, Joseph C; Wang, Lihong; Huettel, Scott A et al. (2014) Neural correlates of cognitive and affective processing in maltreated youth with posttraumatic stress symptoms: does gender matter? Dev Psychopathol 26:491-513

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