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:
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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.
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