This proposal describes a 3 year program to investigate the relations between childhood dysregulation and adult substance abuse, psychopathology, and metabolic syndrome. In this COBRE Project the junior principal investigator, an M.D., Ph.D. with training in child and adolescent psychiatry will work with primary mentor James Hudziak, MD, senior mentors Hugh Garavan, MD and Phil Ades, MD to investigate the metabolic, epigenetic, executive function/decision-making, and psychophysiological mechanisms of a child behavioral syndrome termed """"""""dysregulation."""""""" The study proposes that dysregulation is a common prodrome for a variety of negative adult outcomes (substance abuse, persistent psychopathology, and the cluster of non-psychiatric disorders referred to as """"""""Metabolic Syndrome"""""""" (MS) - diabetes, dyslipedemia, hypertension, and obesity. We propose a model consisting of environmental impact (e.g., low socioeconomic status, chronic adversity) on a genetic predisposition (e.g., family history of self-regulatory problems) affecting the systems involved in self-regulation. The dysregulatory effects in turn affect gluocorticoid and autonomic nervous system (e.g., heart rate variability) responses. We will test this model through the use of a family study approach. In order to do this work, we propose adding measurement of metabolic, epigenetic, executive function/decision-making, and psychophysiological data to parents of children in an ongoing family study of children with dysregulation (NIMH K08MH082116). Through the course of the 3 year study, we will determine the rates of substance use disorders, psychopathology, and metabolic syndrome in the families of children with dysregulation. We will determine the rates of delay discounting (a measure of impulsivity) and the levels of heart rate variability (a measure of autonomic stability) in these children and their families. Using two complementary methods, we will determine the epigenetic profiles in dysregulated children and their family members in two gene promoters known to be associated withs stress reactivity (NR3C1 and FKBP5).

Public Health Relevance

Determining the mechanisms of how behavioral symptoms can lead to later adult outcomes has the potential to significantly reduce morbidity and mortality. Here, we propose to examine a pattern of poor selfregulation in childhood and predict associations with obesity, hypertension, diabetes, substance abuse, and psychiatric disorders in their families. We predict a mechanism involving genes involved in stress reactivity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103644-02
Application #
8734446
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
DUNS #
City
Burlington
State
VT
Country
United States
Zip Code
Harraz, Osama F; Longden, Thomas A; Hill-Eubanks, David et al. (2018) PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells. Elife 7:
Cepeda-Benito, A; Doogan, N J; Redner, R et al. (2018) Trend differences in men and women in rural and urban U.S. settings. Prev Med 117:69-75
D'Alberto, Nicholas; Chaarani, Bader; Orr, Catherine A et al. (2018) Individual differences in stop-related activity are inflated by the adaptive algorithm in the stop signal task. Hum Brain Mapp 39:3263-3276
Villanti, Andrea C; Niaura, Raymond S; Abrams, David B et al. (2018) Preventing Smoking Progression in Young Adults: the Concept of Prevescalation. Prev Sci :
Gaalema, Diann E; Leventhal, Adam M; Priest, Jeffrey S et al. (2018) Understanding individual differences in vulnerability to cigarette smoking is enhanced by attention to the intersection of common risk factors. Prev Med 117:38-42
Ahern, Thomas P; Veres, Katalin; Jiang, Tammy et al. (2018) Adjustment disorder and type-specific cancer incidence: a Danish cohort study. Acta Oncol 57:1367-1372
Fujii, Mayo H; Hodges, Ashley C; Russell, Ruby L et al. (2018) Post-Discharge Opioid Prescribing and Use after Common Surgical Procedure. J Am Coll Surg 226:1004-1012
Ganz, Ollie; Johnson, Amanda L; Cohn, Amy M et al. (2018) Tobacco harm perceptions and use among sexual and gender minorities: findings from a national sample of young adults in the United States. Addict Behav 81:104-108
Phillips, Julie K; Skelly, Joan M; King, Sarah E et al. (2018) Associations of maternal obesity and smoking status with perinatal outcomes. J Matern Fetal Neonatal Med 31:1620-1626
Gaalema, Diann E; Pericot-Valverde, Irene; Bunn, Janice Y et al. (2018) Tobacco use in cardiac patients: Perceptions, use, and changes after a recent myocardial infarction among US adults in the PATH study (2013-2015). Prev Med 117:76-82

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