Prenatal cocaine exposure differentially affects stress responses in girls and boys: Associations with future substance use

Substance use in adolescence is a serious public health problem. Adolescent alcohol and drug use are associated with academic problems, impaired driving, violent behaviors, and increased risk for unprotected sex and HIV transmission (National Institute on Drug Abuse, 2010; Windle et al., 2008), and adolescent substance use is associated with greater cognitive and neural alterations than adult substance use in animal models (Crews, Braun, Hoplight, Switzer, & Knapp, 2000; White, Ghia, Levin, & Swartzwelder, 2000). Further, substance use during adolescence (from early through late adolescence) predicts substance use disorders and antisocial activities in adulthood (Brook, Balka, Ning, & Brook, 2007; Chassin, Pitts, & Prost, 2001). One group of youth who are particularly vulnerable to substance use and abuse are those whowere prenatally exposed to drugs. These youth are exposed to chemical teratogens in utero, and likely other stressors both prenatally and postnatally. According to prenatal stress theory and theories of teratogen exposure, these prenatal insults impact the structure and function of developing systems in the child’s body and brain, create alterations that persist throughout the child’s lifetime, and could lead to risk for substance abuse (Mayes, 1999; Welberg & Seckl, 2001). In addition, youth whose parents use drugs may model their parent’s drug-taking behavior, consistent with social learning theories of child behavior (e.g., Bandura, 1969). Finally, youth with drug-using parents are likely exposed to suboptimal parenting, which is theorized to lead to substance use (e.g., Brook, Brook, Gordon, Whiteman, & Cohen, 1990). Consistent with these theories, research on prenatally cocaine exposed (PCE) youth finds that PCE is linked to increased substance use rates in adolescence in animal model studies (Rocha, Mead, & Kosofksy, 2002) and, recently, in human studies (Bennett, Bendersky, & Lewis, 2007, for boys only; Delaney-Black et al., 2011; Frank et al., 2011). It is important to understand pathways by which prenatal exposures lead to increased risk for substance use in adolescence. One potential pathway may be through PCE effects on stress arousal systems. We propose a conceptual model (see Figure 1) positing that prenatal exposure to cocaine, particularly in the presence of compromised postnatal caregiving environments, leads youth to develop altered emotional and physiological arousal in response to stress. Theories of PCE effects have proposed that cocaine specifically impacts developing monaminergic neurotransmitter pathways in the fetus, pathways directly involved in arousal regulation (Mayes, 2002). Our model posits that PCE youth would specifically show alterations in arousal regulation, including arousal in response to stress (see also Mayes, 2002). We propose that these altered stress responses (among other factors, such as peer environments; Hawkins, Catalano, & Miller, 1992) then lead to risk for youth substance use. We propose, consistent with diathesis-stress models of substance use (e.g., Tarter et al., 1999) that the altered stress responses in PCE youth may lead the youth to react to environmental stressors in ways that lead to substance use. Figure 1 Conceptual model of associations between prenatally cocaine exposed (PCE) status, adolescent stress response, and adolescent substance use. This may occur in one of two ways. First, PCE youth may be overly aroused by stress and then may seek out substances to downregulate their heightened arousal responses, consistent with self-medication and stress-reduction theories of substance use etiology (Khantzian, 1985; Sinha, 2001). Second, PCE youth may be underaroused by stress and may seek out substances to upregulate their blunted physiological arousal, consistent with sensation-seeking theories of substance use (Wills, Vaccaro, & McNamara, 1994). In our conceptual model, we propose that the pathway from PCE to stress responses and from stress responses to substance use may differ by child gender, with at-risk girls taking a heightened arousal response/self-medication pathway and at-risk boys taking an underaroused/sensation-seeking pathway, as we discuss below (see Gender Section). Finally, we propose that negative caregiving environments may exacerbate effects of PCE on stress response and substance use outcomes, as has been proposed (and found) previously in the prenatal drug exposure literature (Bada et al., 2007; Behnke et al., 2006).