Early social stress, novelty seeking, and impulsive behavior

Summary

Principal Investigator: David M Lyons
Abstract: DESCRIPTION (provided by applicant): Novelty seeking behavior promotes the ability to discover and construct new knowledge about the environment. Greater preferences for novelty during infancy predict higher scores on tests of intelligence, language, memory, and speed of information processing in children and young adults. Novelty seeking can be costly, however, as it increases the prevalence of reckless driving, pathological gambling, unprotected sex, under-age drinking, and other forms of alcohol and drug abuse. Recently, we discovered that novelty seeking in an animal model mediates the effects of early social stress on subsequent resistance to extinction of a conditioned place preference for cocaine. Our preliminary evidence further suggests that early exposure to social stress induces long-lasting downregulation of dopamine D2 receptor (DRD2) gene expression in ventral but not dorsal striatum. Diminished ventral striatal DRD2 availability determined in vivo by positron emission tomography (PET) has been linked in humans and animal models to novelty seeking and related maladaptive forms of anticipatory impulsivity, but not in the context of early social stress. Therefore, we plan to test the hypothesis that early social stress downregulates DRD2 gene expression in ventral striatum via epigenetic mechanisms (i.e., increased DNA methylation) and thereby increases anticipatory impulsivity. Specifically, we address the following three aims. Aim 1. Determine whether early social stress increases DRD2 gene promoter methylation in ventral but not dorsal striatum assessed by bisulfite sequencing of DNA from striatal brain tissues. Aim 2. Determine whether early social stress decreases DRD2 availability in ventral but not dorsal striatum assessed in vivo by positron emission tomography. Aim 3. Determine whether early social stress increases anticipatory impulsivity without impairing non-anticipatory forms of impulsive behavior. The studies designed to address these aims will provide mechanistic insights for understanding the pathways that mediate the long-term effects of early social stress on broadly important health-related aspects of behavior. PUBLIC HEALTH RELEVANCE: The public health impacts of understanding the mechanisms that mediate the effects of social stress on health-related behavior are potentially quite high. According to the World Health Organization, stress- related mental health disorders will be the second leading cause of all medical disabilities by the year 2020. The American Institute of Stress has determined that currently more than 70% of all medical visits are stress-related and collectively cost the nation 42 billion dollars each year. Consequently, there is an urgent need for new mechanistic insights to guide the development of public health policies and interventions designed to alleviate the detrimental long-term effects of exposure to early social stress.
Funding Period: 2012-09-01 - 2015-07-31
more information: NIH RePORT

Top Publications

  1. pmc Coping changes the brain
    Jordan M Nechvatal
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine Stanford, CA, USA Neurosciences Program, Stanford University School of Medicine Stanford, CA, USA
    Front Behav Neurosci 7:13. 2013

Detail Information

Publications1

  1. pmc Coping changes the brain
    Jordan M Nechvatal
    Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine Stanford, CA, USA Neurosciences Program, Stanford University School of Medicine Stanford, CA, USA
    Front Behav Neurosci 7:13. 2013
    ..These studies will advance our understanding of coping as a learning process and provide mechanistic insights for the development of new interventions that promote stress coping skills...

Research Grants30

  1. MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISM
    Fulton T Crews; Fiscal Year: 2013
    ..The ARC will conduct, promote, support, and mentor research on alcoholic pathology and educate broad groups of health professionals and youth in North Carolina. ..
  2. Neurocircuitry Underlying DBS Effects in OCD: A Window Into Mechanisms of Action
    Suzanne N Haber; Fiscal Year: 2013
    ..Results from these studies will also make important new contributions to our understanding of the basic mechanisms of DBS. ..
  3. Maternal and Child Health in Poor Countries: Evidence from Randomized Evaluations
    ESTHER DUFLO; Fiscal Year: 2013
    ..It will compare the impact of this program with that of a government program that gives women financial incentives for institutional delivery. ..
  4. CDART - Center for Drug Abuse Research Translation
    Michael T Bardo; Fiscal Year: 2013
    ..The long-range goal is to improve the design and implementation of targeted anti-drug preventive interventions. ..
  5. CENTER FOR CHILD ENVIRONMENTAL HEALTH RISKS RESEARCH
    Elaine M Faustman; Fiscal Year: 2013
    ..The Center also includes junior investigators, new scientists since the 2003 Center renewal, and a Faculty Development Investigator. The Internal Steering Committee in comprised of a number of Center investigators and directors. ..
  6. Center for Novel Therapeutics for HIV-Associated Cognitive Disorders
    Justin C McArthur; Fiscal Year: 2013
    ..5. To identify and validate surrogate biomarkers based on proteomics and lipomics. ..
  7. Activity-Dependent Synaptic and Circuit Plasticity
    Robert C Malenka; Fiscal Year: 2013
    ..Such information will lead to a better understanding of the causes of mental illness and eventually to the development of more efficacious treatments. ..
  8. Epigenetic Marks of Cocaine Addiction
    Gustavo Turecki; Fiscal Year: 2013
    ..abstract_text> ..
  9. Enduring Effects of Early-Life Serotonin Signaling
    Randy D Blakely; Fiscal Year: 2013
    ..abstract_text> ..
  10. Methamphetamine Abuse Research Center
    AARON J JANOWSKY; Fiscal Year: 2013
    ..Data and samples are shared and compared across components. Thus, the MARC addresses clinically relevant themes using integrated, innovative, multidisciplinary, and translational approaches. ..
  11. MARC: Risk Mechanisms in Alcoholism and Comorbidity
    Andrew C Heath; Fiscal Year: 2013
    ..abstract_text> ..
  12. Aging and Dementia in Adults with Down Syndrome
    Wayne P Silverman; Fiscal Year: 2013
    ..Further, some findings may have direct implications for promoting more successful aging for adults with DS. ..
  13. Emory Alcohol and Lung Biology Center
    DAVID MARSHALL GUIDOT; Fiscal Year: 2013
    ..abstract_text> ..
  14. RADIOLOGICAL PHYSICS CENTER
    David S Followill; Fiscal Year: 2013
    ..Thus, the RPC's overall QA program impacts not only on clinical trial patients, but on the quality of all patients treated at the institution. ..
  15. Iowa Cochlear Implant Clinical Research Center Project VI
    Bruce Jay Gantz; Fiscal Year: 2013
    ..The five research projects are highly integrated and depend on data from each other to answer the experimental questions. ..
  16. EARLY INDICATORS OF LATER WORK LEVELS, DISEASE AND DEATH
    Dora L Costa; Fiscal Year: 2013
    ..Project 4 deals with the differences across urban and rural areas in the process of aging. ..
  17. Alzheimer's Disease Research Center
    Douglas R Galasko; Fiscal Year: 2013
    ..It will provide an environment and core resources to enhance research, foster professional and community training, and coordinate interdisciplinary research. ..
  18. Neuronal CpG Methylation During Development in Normal and Adverse Environment
    Miklos Toth; Fiscal Year: 2013
    ..These groups of genes form functional networks and pathways that are essential to understand the role of DNA methylation in neuronal development and psychiatric disease. ..
  19. NOVEL MEDICATION APPROACHES FOR SUBSTANCE ABUSE
    HERBERT DAVID KLEBER; Fiscal Year: 2013
    ..abstract_text> ..
  20. Stimulant Pharmacotherapy: Noradrenergic Targets
    THOMAS RICHARD KOSTEN; Fiscal Year: 2013
    ..5. To attract and train new drug abuse pharmacotherapy investigators through our Center's Core facilities and projects. 6. To disseminate our findings through education and international collaborations. ..
  21. Center for the Neurobiology of Addiction Treatment
    Steven R Childers; Fiscal Year: 2013
    ..These projects utilize several animal models and technologies uniquely developed by the Center investigators over the previous years of its funding history. ..