ReviewDesperately driven and no brakes: Developmental stress exposure and subsequent risk for substance abuse
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)
Trajectories of brain development: point of vulnerability or window of opportunity?
Neurosci. Biobehav. Rev.
(2003)Stimulants and the developing brain
Trends Pharmacol. Sci.
(2005)- et al.
RNA and DNA synthesis in developing rat brain: hormonal influences
Psychoneuroendocrinology
(1978) - et al.
Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi
Eur. J. Pharmacol.
(2006) - et al.
Gender-specific effect of maternal deprivation on anxiety and corticotropin-releasing hormone mRNA expression in rats
Brain Res. Bull.
(2003) Granule cell genesis in the hippocampus of rats treated neonatally with hydrocortisone
Neuroscience
(1980)- et al.
Enhanced nucleus accumbens dopamine and plasma corticosterone stress responses in adult rats with neonatal excitotoxic lesions to the medial prefrontal cortex
Neuroscience
(2000) - et al.
Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse—a preliminary report
Biol. Psychiatry
(1997) - et al.
Variations in maternal care in infancy regulate the development of stress reactivity
Biol. Psychiatry
(2000) - et al.
The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat
Neuropsychopharmacology
(2000)
Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder
Biol. Psychiatry
Adverse childhood experiences and the risk of depressive disorders in adulthood
J. Affect. Disord.
Adolescent cortical development: a critical period of vulnerability for addiction
Pharmacol. Biochem. Behav.
Reward, motivation, and reinforcement learning
Neuron
A. E. Bennett Research Award. Developmental traumatology. Part I. Biological stress systems
Biol. Psychiatry
Sex differences in brain maturation in maltreatment-related pediatric posttraumatic stress disorder
Neurosci. Biobehav. Rev.
Developmental traumatology. Part II. Brain development
Biol. Psychiatry
Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study
Biol. Psychiatry
Urinary catecholamine excretion in sexually abused girls
J. Am. Acad. Child Adolesc. Psychiatry
Stress-induced sensitization to amphetamine and morphine psychomotor effects depend on stress-induced corticosterone secretion
Brain Res.
Social isolation-induced enhancement of the psychomotor effects of morphine depends on corticosterone secretion
Brain Res.
Repeated corticosterone administration sensitizes the locomotor response to amphetamine
Brain Res.
Amygdala and nucleus accumbens in responses to receipt and omission of gains in adults and adolescents
Neuroimage
Childhood sexual abuse and psychiatric disorder in young adulthood. II. Psychiatric outcomes of childhood sexual abuse
J. Am. Acad. Child Adolesc. Psychiatry
Serum dopamine beta hydroxylase and maltreatment in psychiatrically hospitalized boys
Child Abuse Negl.
A neuroendocrine role in cocaine reinforcement
Psychoneuroendocrinology
Stress and hippocampal neurogenesis
Biol. Psychiatry
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.
Regulation of firing of dopaminergic neurons and control of goal-directed behaviors
Trends Neurosci.
Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems
Pharmacol. Biochem. Behav.
Dementia severity and Lewy bodies affect circadian rhythms in Alzheimer disease
Neurobiol. Aging
Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders
Neuroscience
The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies
Biol. Psychiatry
The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma
Biol. Psychiatry
Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism
Biol. Psychiatry
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
Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission
Neuron
Chronic neonatal isolation stress enhances cocaine-induced increases in ventral striatal dopamine levels in rat pups
Brain Res. Dev.
Drug dependence: stress and dysregulation of brain reward pathways
Drug Alcohol Depend.
Hormonal and humoral influences on brain development
Psychoneuroendocrinology
Validity of pilot adult ADHD Self-Report Scale (ASRS) to Rate Adult ADHD symptoms
Ann. Clin. Psychiatry
Cocaine-but not food-seeking behavior is reinstated by stress after extinction
Psychopharmacology (Berl.)
Maturational increases in c-fos expression in the ascending dopamine systems
Synapse
Enduring neurochemical effects of early maternal separation on limbic structures
Ann. NY Acad. Sci.
Delayed effects of early stress on hippocampal development
Neuropsychopharmacology
Stress, sensitive periods and maturational events in adolescent depression
Trends Neurosci.
Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development
J. Neuropsychiat. Clin. Neurosci.
Functional heterogeneity in dopamine release and in the expression of Fos-like proteins within the rat striatal complex
Eur. J. Neurosci.
Brain glucocorticoid receptors and their role in behavioural teratogenicity of synthetic glucocorticoids
Arch. Toxicol. Suppl.
Self-reported abuse history and adolescent problem behaviours. II. Alcohol and drug use
J. Adolesc. Health
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