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
Taghavi, Taraneh; Arger, Christopher A; Heil, Sarah H et al. (2018) Longitudinal Influence of Pregnancy on Nicotine Metabolic Pathways. J Pharmacol Exp Ther 364:238-245
Kurti, Allison N; Redner, Ryan; Bunn, Janice Y et al. (2018) Examining the relationship between pregnancy and quitting use of tobacco products in a U.S. national sample of women of reproductive age. Prev Med 117:52-60
Taghavi, Taraneh; Arger, Christopher A; Heil, Sarah H et al. (2018) Cigarette consumption and biomarkers of nicotine exposure during pregnancy and postpartum. Addiction 113:2087-2096
Ades, Philip A; Gaalema, Diann E (2018) Geographic Variations in Cardiac Rehabilitation Use: Regional Variations in Medical Care or in Patient Behaviors? Circulation 137:1909-1911
Harraz, Osama F; Longden, Thomas A; Dabertrand, Fabrice et al. (2018) Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIP2 depletion. Proc Natl Acad Sci U S A 115:E3569-E3577
Abudayyeh, Haneen S; Glasser, Allison M; Johnson, Amanda L et al. (2018) Social and substance use correlates of adult hookah use, 2016. Addict Behav 79:39-44
Parker, Maria A; Villanti, Andrea C; Quisenberry, Amanda J et al. (2018) Tobacco Product Harm Perceptions and New Use. Pediatrics 142:
Rengo, Jason L; Savage, Patrick D; Barrett, Trace et al. (2018) Cardiac Rehabilitation Participation Rates and Outcomes for Patients With Heart Failure. J Cardiopulm Rehabil Prev 38:38-42
Riley, Hayden; Headley, Samuel; Winter, Christa et al. (2018) Effect of Smoking Status on Exercise Perception and Intentions for Cardiac Rehabilitation Enrollment Among Patients Hospitalized With an Acute Cardiac Condition. J Cardiopulm Rehabil Prev 38:286-290
Parker, Maria A; Ochalek, Taylor A; Rose, Gail L et al. (2018) Feasibility of an interactive voice response system for daily monitoring of illicit opioid use during buprenorphine treatment. Psychol Addict Behav 32:956-960

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