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

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.

Figure 1

“Desperately driven with no brakes” is illustrated by this circuit of the stress-exposed brain. Under non-addictive states, the nucleus accumbens receives input from a number of brain regions, including the hippocampus and the prefrontal cortex. These inputs serve to modulate the response of the nucleus accumbens in a manner that is controlled, flexible, and contextually relevant. Following stress exposure, this system is less well modulated. Hippocampal gating of cortical inputs is reduced. Moreover, the prefrontal cortex inputs respond more selectively to drug-conditioned cues, which is vital is a critical factor leading to for relapse.

Figure 2

Age of first use of various types of abusable substances. Data are plotted as the cumulative percentage of total users for a given type of abusable substance by age of first use. Data were collected by the National Survey on Drug Use and Health, 2002 (www.samhsa.gov/oas/p0000016.htm) and were extracted for this graph using the data-base search engine provided by the Inter-university Consortium for Political and Social Research (www.icpsr.umich.edu).