Structural Stressors, Reward Related Decision Making and Substance Use Risk

Substance use disorders (SUDs) are common, and are associated with significant impairment and public health costs (Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health 2015). Adolescence is a key developmental period involving significant neurodevelopmental changes and is a critical risk period for the initiation of substance use and related negative outcomes, including substance use problems in adulthood (Andrews, Ahmed, \& Blakemore, 2021; Blakemore, 2012; Dawson, Goldstein, Chou, Ruan, \& Grant, 2008; Gray \& Squeglia, 2018; Guttmannova et al., 2011; Irons, Iacono, \& McGue, 2015; McCabe et al, 2022). Improved understanding of the neurocognitive mechanisms of substance use risk could lead to novel approaches to prevention.

The effects of structural structures (SS) are harmful. Between 50-75% of minoritized populations in the US report discriminatory treatment (Lee, Perez, Boykin, \& Mendoza-Denton, 2019), and experiences of ethnoracial discrimination during childhood and adolescence are associated with increased substance use in youth (e.g. Benner, Wang, Shen, Boyle, Polk, \& Cheng, 2018). While the impact of interpersonal discrimination on substance use risk in youth is important, it focuses on perceptions of experiences rather than the ways that minoritized individuals are systematically disadvantaged. Thus, we plan to measure the impact of indicators of structural racism on substance use risk, while controlling for experiences of discrimination, to determine the impact of SS indicators over and above individual experiences. Structural factors impact SUD risk: The impact of SS indicators on adolescent substance use risk is currently unknown, however, ethnoracial inequities have been documented in structural indices associated with increased substance use risk, including ethnoracial inequities in 1) household income in the US (Rivenbark et al, 2019), 2) high school dropout rates (Maynard, Salas-Wright, \& Vaughn, 2015; Townsend, Flisher, \& King, 2007), and 3) neighborhood violence (Fagan, Wright, \& Pinchevsky, 2014; Lambert, Brown, Phillips, \& Ialongo, 2004). Thus, generating a composite of indicators of SS using racial differences in census tract level income and educational attainment, and precinct level murder rates will provide an SS measure relevant for adolescent substance use risk.

Structural factors impact brain development. Neighborhood-level structural factors have been shown to impact brain structure and function (Maxwell, Taylor, \& Barch, 2022; Taylor, Cooper, Jackson, \& Barch, 2020), suggesting it is plausible that SS is related to neurodevelopmental changes. Neuroscience informs structural change. Results from neuroscience have influenced policy, e.g. child tax credits (e.g. Vickers, Zamani-Hank, \& Margerison, 2022) and court decisions, e.g. juvenile sentencing practices (e.g. Miller v. Alabama SC. 2012). Thus, neuroscience plays an important role in motivating and shaping structural-level changes, particularly for children and adolescents, underlining the importance of examining neural correlates of SS indicators.

Individual Differences in Reward-Related Decision Making Can Contribute to Substance Use Risk. Mechanisms by which greater exposure to SS could increase substance use are not known. Individuals with SUDs tend to have to prefer smaller, sooner over larger, later rewards - i.e. steeper delay discounting, compared to individuals without SUDs or related problems (e.g. Amlung, Vedelago, Acker, Balodis, \& MacKillop, 2017.). Steeper delay discounting has been interpreted as a sign of maladaptive impulsivity (Amlung, Vedelago, Acker, Balodis, \& MacKillop, 2017). However, learning to wait for larger, later rewards is theorized to emerge developmentally alongside a belief in a just world, as it is only sensible to wait for larger rewards if people get what they deserve (Lerner \& Miller, 1978). Belief in a just world relates to reward related decision making; both 1) exposure to unjust scenarios and 2) reduced belief in a just world is associated with steeper delay discounting (Lerner \& Miller, 1978). Thus, growing up in an unjust environment with high levels of SS, may promote steeper delay discounting. Steeper delay discounting may help secure available rewards in unjust environments. However, given the well-established link between steeper delay discounting and SUDs (Amlung, Vedelago, Acker, Balodis, \& MacKillop, 2017), when the reward is a substance, and immediate use is chosen over long-term health outcomes, this adaptation to the environment could increase the odds of risky substance use (Kim-Spoon et al, 2019). Improved understanding of how SS leads to increased substance use risk could inform novel prevention/intervention efforts at the structural level. For example, if steeper delay discounting moderates the relationship between higher levels of SS indicators and increased substance use risk, interventions could target 1) structural inequality, particularly the indicators measured, and 2) reward related decision making (Stein et al, 2016) to reduce the harmful effects of SS (Stein et al, 2016).

Protective Factors: Structural \& Family-Level Protective Factors. Area level protective factors may buffer the negative effects of SS on substance use risk, including the availability of churches and the percentage of minority owned businesses. The number of neighborhood churches per capita have been associated with lower likelihood of SUDs (Stockdale et al, 2007). Similarly, the number of minority-owned businesses in a neighborhood has a positive effects. For example, an increased number of Latine-owned businesses relates to reduced property crime rates (Stansfield, 2014). Thus, we will examine if the number of local, churches and Latine-owned businesses in the area buffers the effect of SS indicators on neural structure and function. Family-level processes, such as higher parental monitoring, parent-child communication and familism are associated with reduced substance use risk in Latine youth (Pokhrel, Unger, Wagner, Ritt-Olson, \& Sussman, 2008; German, Gonzales, \& Dumka, 2009). Examining the buffering effect of familial-level factors on the relationship between SS and neurodevelopment will inform if targeting family processes can help protect against the negative impact of SS.

The Boricua Youth Study, an opportunity: The Boricua Youth Study (BYS) started in 2000 with the goal of learning more about the mental health of Puerto Rican youth living in two contexts: San Juan, Puerto Rico, and the South Bronx, New York. Longitudinal data were collected over 3 Waves, between 2001-2004. The original youth participants of the BYS now have children, allowing a second generation of BYS to participate in research. Thus, working with BYS is an opportunity to: 1) measure SS indicators in two distinct contexts and 2) isolate the impact of SS indicators on substance use, by controlling for familial factors. This study will generate separate measures of SS indicators, with particular relevance to substance use risk-related outcomes, for Puerto Rican youth living in two contexts: in the US mainland and in PR. Thus, we will be able to 1) compare the structure of SS indicators between the two contexts; 2) determine if certain SS indices contribute more to substance use risk in one site than another. Intergenerational transference of substance use is well established. Furthermore, it is possible that familial history of SUD could influence youths' delay discounting choices, as has been found empirically (Dougherty et al, 2014). Therefore, to isolate the impact of SS indicators on brain structure, delay discounting related brain activity, and SUD risk, it is crucial to account for familial SUD risk factors. Other large datasets do not have prospectively captured data regarding familial SUD risk factors. Therefore, working with the BYS-ECHO will add key complementary information by enabling us to directly control for prospectively captured familial SUD risk factors, e.g. parental SUD and impulsivity.

R61 Specific Aims: Proof of Concept of relationship of indicators of SS with Neurocognitive Mechanisms: We will invite 72 children (aged 11-14, 50% female, 50% from SBx, 50% from PR), to provide home address history (last 5 yrs), substance use risk, belief in a just world and magnetic resonance imaging (MRI) for brain structure and DD-related brain function. Higher levels of SS indicators will relate to: Aim 1, Hypothesis 1 (H1): adolescent brain structure: lower grey matter volume of superior frontal, dorsal lateral and medial prefrontal cortices; Aim 2, H2: Steeper DD and less DD-related activity in dorsal medial prefrontal and anterior cingulate cortices, ventral striatum and insula; Aim 3, H3: Reduced belief in a just world. A moderate effect size association (r > 0.30) found for H1, H2, or H3 will justify progression to the R33 phase.