Review
Desperately driven and no brakes: Developmental stress exposure and subsequent risk for substance abuse

https://doi.org/10.1016/j.neubiorev.2008.09.009Get rights and content

Abstract

Adverse life events are associated with a wide range of psychopathology, including an increased risk for substance abuse. In this review, we focus on the inter-relationship between exposure to adversity and brain development, and relate this to enhanced windows of vulnerability. This review encompasses clinical and preclinical data, drawing evidence from epidemiological studies, morphometric and functional imaging studies, and molecular biology and genetics. The interaction of exposure during a sensitive period and maturational events produces a cascade that leads to the initiation of substance use at younger ages, and increases the likelihood of addiction by adolescence or early adulthood. A stress-incubation/corticolimbic dysfunction model is proposed based on the interplay of stress exposure, development stage, and neuromaturational events that may explain the seeking of specific classes of drugs later in life. Three main factors contribute to this age-based progression of increased drug use: (1) a sensitized stress response system; (2) sensitive periods of vulnerability; and (3) maturational processes during adolescence. Together, these factors may explain why exposure to early adversity increases risk to abuse substances during adolescence.

Introduction

Childhood adversity, stemming from abuse, parental loss, witnessing of domestic violence or household dysfunction is a major cause of poor mental and physical health (Chapman et al., 2004, Dube et al., 2003, Felitti, 2002). One major consequence of early adversity is a markedly increased risk for substance use, abuse, and dependence (Dube et al., 2003). We, and others, have proposed that childhood abuse produces a cascade of physiological and neurohumoral events that alter trajectories of brain development (e.g., Andersen, 2003, Teicher et al., 2002), and that the neurobiological consequences of exposure to childhood abuse parallel the effects of exposure to developmental stress in preclinical studies (Teicher et al., 2006). The aim of this review is to summarize some of the recently reported effects of early stress on brain development in animals and man, focusing on potential associations that may help to elucidate causal links between early adversity and subsequent abuse of alcohol, nicotine, and illicit drugs. A major emphasis of this review will be on developmental/temporal factors, recognizing that drug abuse is a “developmental disorder” in which there are windows of vulnerability when exposure to drugs of abuse are more likely to lead to abuse and dependence (Chambers et al., 2003, Wagner and Anthony, 2002). To this framework we add new evidence for the existence of sensitive periods in which discrete brain regions are maximally susceptible to the effects of stress, and emphasize the substantial lag period that may intervene between time of exposure and manifestation of adverse consequences.

Section snippets

Developmental stress and substance abuse epidemiology

The impact of childhood adversity is shown most clearly in the Adverse Childhood Experiences (ACE) study based on retrospective surveys of 17,337 members of the Kaiser-Permanente HMO in San Diego (Chapman et al., 2004, Dube et al., 2003, Felitti, 2002). The number of different ACEs ‘dose-dependently’ increases symptoms or disease prevalence. Population attributable risk associated with early adversity was 50% for drug abuse, 54% for current depression, 65% for alcoholism, 67% for suicide

The neurobiology of substance abuse—a very basic framework

Drugs that are considered rewarding produce a number of changes that are involved in the addiction process as mediated primarily by a few key brain regions (Hyman et al., 2006). First, the hedonic, pleasurable feeling that links all drugs of abuse is associated with increased dopamine in the nucleus accumbens (Dayan and Balleine, 2002, Koob and Swerdlow, 1988, Weiss, 2005). Second, the hippocampus consolidates the process of learning about this liking, and maintains the memory of the

A stress-incubation/corticolimbic development cascade hypothesis of drug abuse vulnerability

Based on the literature reviewed herein, the high rates of drug addiction following childhood maltreatment may be explained partly by the stress-incubation/corticolimbic developmental cascade hypothesis (Andersen and Teicher, 2008) as applied to drugs of abuse. This hypothesis proposes that exposure to early life stress predisposes individuals to abuse drugs at an earlier age via the three following tenets:

  • 1.

    Compulsive drug use increases due to a highly reactive hypothalamic–pituitary–adrenal

Conclusions

Exposure to early adversity will shift drug-seeking to an earlier age within this window, but whether these shifts are due to changes in gating of the hippocampus (early stress), elevated dopamine in the accumbens (early stress), or synaptic changes in the prefrontal cortex (adolescent stress) remains to be determined. A desperately driven model of drug use without brakes is shown in Fig. 1. Together, the data reviewed in this study suggest that the reward system is revved up. A dysregulated

Acknowledgements

Supported, in part, by awards from NARSAD (2001, 2002, 2005), NIDA RO1DA-016934, RO1DA-017846), NIMH (RO1MH-66222) and the Simches and Rosenberg Families. MHT was a John W. Alden Trust Investigator.

References (174)

  • V.G. Carrion et al.

    Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder

    Biol. Psychiatry

    (2001)
  • D.P. Chapman et al.

    Adverse childhood experiences and the risk of depressive disorders in adulthood

    J. Affect. Disord.

    (2004)
  • F. Crews et al.

    Adolescent cortical development: a critical period of vulnerability for addiction

    Pharmacol. Biochem. Behav.

    (2007)
  • P. Dayan et al.

    Reward, motivation, and reinforcement learning

    Neuron

    (2002)
  • M.D. De Bellis et al.

    A. E. Bennett Research Award. Developmental traumatology. Part I. Biological stress systems

    Biol. Psychiatry

    (1999)
  • M.D. De Bellis et al.

    Sex differences in brain maturation in maltreatment-related pediatric posttraumatic stress disorder

    Neurosci. Biobehav. Rev.

    (2003)
  • M.D. De Bellis et al.

    Developmental traumatology. Part II. Brain development

    Biol. Psychiatry

    (1999)
  • M.D. De Bellis et al.

    Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study

    Biol. Psychiatry

    (2002)
  • M.D. De Bellis et al.

    Urinary catecholamine excretion in sexually abused girls

    J. Am. Acad. Child Adolesc. Psychiatry

    (1994)
  • V. Deroche et al.

    Stress-induced sensitization to amphetamine and morphine psychomotor effects depend on stress-induced corticosterone secretion

    Brain Res.

    (1992)
  • V. Deroche et al.

    Social isolation-induced enhancement of the psychomotor effects of morphine depends on corticosterone secretion

    Brain Res.

    (1994)
  • V. Deroche et al.

    Repeated corticosterone administration sensitizes the locomotor response to amphetamine

    Brain Res.

    (1992)
  • M. Ernst et al.

    Amygdala and nucleus accumbens in responses to receipt and omission of gains in adults and adolescents

    Neuroimage

    (2005)
  • D.M. Fergusson et al.

    Childhood sexual abuse and psychiatric disorder in young adulthood. II. Psychiatric outcomes of childhood sexual abuse

    J. Am. Acad. Child Adolesc. Psychiatry

    (1996)
  • M. Galvin et al.

    Serum dopamine beta hydroxylase and maltreatment in psychiatrically hospitalized boys

    Child Abuse Negl.

    (1995)
  • N.E. Goeders

    A neuroendocrine role in cocaine reinforcement

    Psychoneuroendocrinology

    (1997)
  • E. Gould et al.

    Stress and hippocampal neurogenesis

    Biol. Psychiatry

    (1999)
  • A.P. Goursaud et al.

    Do neonatal bilateral ibotenic acid lesions of the hippocampal formation or of the amygdala impair HPA axis responsiveness and regulation in infant rhesus macaques (Macaca mulatta)?

    Brain Res.

    (2006)
  • A.A. Grace et al.

    Regulation of firing of dopaminergic neurons and control of goal-directed behaviors

    Trends Neurosci.

    (2007)
  • F.S. Hall et al.

    Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems

    Pharmacol. Biochem. Behav.

    (1998)
  • D.G. Harper et al.

    Dementia severity and Lewy bodies affect circadian rhythms in Alzheimer disease

    Neurobiol. Aging

    (2004)
  • L.E. Haynes et al.

    Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders

    Neuroscience

    (2001)
  • C. Heim et al.

    The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

    Biol. Psychiatry

    (2001)
  • C. Heim et al.

    The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma

    Biol. Psychiatry

    (2008)
  • S.Y. Hill et al.

    Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism

    Biol. Psychiatry

    (2000)
  • W.C. Holmes

    Association between a history of childhood sexual abuse and subsequent, adolescent psychoactive substance use disorder in a sample of HIV seropositive men

    J. Adolesc. Health

    (1997)
  • P.W. Kalivas et al.

    Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission

    Neuron

    (2005)
  • T.A. Kosten et al.

    Chronic neonatal isolation stress enhances cocaine-induced increases in ventral striatal dopamine levels in rat pups

    Brain Res. Dev.

    (2003)
  • M.J. Kreek et al.

    Drug dependence: stress and dysregulation of brain reward pathways

    Drug Alcohol Depend.

    (1998)
  • J.M. Lauder

    Hormonal and humoral influences on brain development

    Psychoneuroendocrinology

    (1983)
  • L.A. Adler et al.

    Validity of pilot adult ADHD Self-Report Scale (ASRS) to Rate Adult ADHD symptoms

    Ann. Clin. Psychiatry

    (2006)
  • S.H. Ahmed et al.

    Cocaine-but not food-seeking behavior is reinstated by stress after extinction

    Psychopharmacology (Berl.)

    (1997)
  • S.L. Andersen et al.

    Maturational increases in c-fos expression in the ascending dopamine systems

    Synapse

    (2001)
  • S.L. Andersen et al.

    Enduring neurochemical effects of early maternal separation on limbic structures

    Ann. NY Acad. Sci.

    (1999)
  • S.L. Andersen et al.

    Delayed effects of early stress on hippocampal development

    Neuropsychopharmacology

    (2004)
  • S.L. Andersen et al.

    Stress, sensitive periods and maturational events in adolescent depression

    Trends Neurosci.

    (2008)
  • S.L. Andersen et al.

    Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development

    J. Neuropsychiat. Clin. Neurosci.

    (2008)
  • M. Barrot et al.

    Functional heterogeneity in dopamine release and in the expression of Fos-like proteins within the rat striatal complex

    Eur. J. Neurosci.

    (1999)
  • O. Benesova et al.

    Brain glucocorticoid receptors and their role in behavioural teratogenicity of synthetic glucocorticoids

    Arch. Toxicol. Suppl.

    (1985)
  • L.S. Bensley et al.

    Self-reported abuse history and adolescent problem behaviours. II. Alcohol and drug use

    J. Adolesc. Health

    (1999)
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