Charting the Neural Pathways From Discrimination to Mental Health Disparities

Despite the well-documented association between depression, anxiety, and posttraumatic stress disorder (PTSD) and discrimination for minoritized identity characteristics such as race, body size or shape, sexual orientation, or national origin, there has been insufficient attention to the mechanisms of this association. Prominent models postulate that the experience of discrimination impairs health through generating a stress response (1). Managing this physiologically taxing response then necessitates affect regulation, potentially through the involvement of neural cognitive control systems. Notably, periods of identity development and changes in affective and cognitive control systems, such as adolescence, could involve particular sensitivity to the effects of discrimination. In this issue, Grey et al. (2) address this long-standing gap with a longitudinal study investigating whether the pattern of discrimination over time is related to adolescents’ depression, anxiety, and PTSD symptoms, and whether this relation is mediated by stress-related activation of cognitive control regions. The study’s sample size, trajectory modeling of exposure to discrimination, and operationalization of discrimination in several ways (presence, cumulative quantity, and type) create a rigorous test and a unique opportunity to address this important aspect of mental health disparities.

The findings of this innovative paper replicated the association between discrimination and distress symptoms and also indicated that greater dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe (IPL) response to a functional MRI (fMRI) task involving generic stress 1) was related to exposure to discrimination and 2) statistically mediated the associations of discrimination with depression and PTSD. Interestingly, these mediation effects revealed higher DLPFC and IPL reactivity in association with discrimination and a “subsequent” decrease in symptoms, raising the possibility that adolescents who react to discrimination with engagement in cognitive control systems can generate a protective response to manage stress and reduce affective distress. The IPL’s role in social cognition and coordination across levels of cognitive processing (3) also underscores the potential value of flexible and integrated response in neural systems. The association of discrimination with higher DLPFC and IPL reactivity indicates that on average, adolescents who have experienced discrimination may have developed aspects of executive function that are helpful in managing stress experiences. Furthermore, even though neural activation only mediated the influence of general discrimination and not subtypes of discrimination, adolescents who experienced discrimination based on race, sexual and gender minority identity, or weight had higher response in these cognitive control regions, suggesting that certain types of discrimination could elicit engagement of self-regulation resources.

Discrimination stress could be more harmful than other types of stress at similar intensity, and there is likely a special vulnerability for certain people, at certain points in development, and to certain types of discrimination. We need to learn a great deal more before determining how pathways to mental health disparities play out. Extant models of the effects of discrimination on mental health disparities have also proposed varying pathways, including postulating that the critical process involves accumulation of stress, persistence of stress, or sensitization to stress (4). Yet, findings to date are unsatisfying for testing these competing (or interacting) pathways because of the widespread limitation of cross-sectional designs. While the findings by Grey et al. provide hints about which neural systems are involved in these disparities and which experiences of discrimination could be most harmful, the study’s assessment of symptoms and neural reactivity to stress at a single, co-occurring time point precludes the ability to model trajectories of neural reactivity or symptoms and to draw conclusions about the temporal unfolding of discrimination’s influence and mechanisms.

There are many critical directions for the research that will follow from this important step in examining neural mechanisms of mental health disparities in minoritized populations. Notably, the puzzling partial mediation and possible suppression finding—that is, the finding that the association between discrimination and depression and PTSD appeared stronger when the mediating factor of brain function was included than when the direct association was tested without mediation—hints that associations among these constructs are nuanced and multiply determined. Suppression effects occur when the inclusion of a putative mediating variable, rather than having the hypothesized effect of explaining the association between the predictor and outcome variables by reducing the strength of their association, ends up increasing the strength of the association. While the Grey et al. findings do not meet the formal criteria for a suppression effect because brain function was related to affective outcomes, they nonetheless reveal that function in cognitive control systems might have some influence but is not sufficiently or directly influential in explaining associations. There is more to the discrimination–distress symptom story than just the cognitive control system’s activation to stress. Other neural systems relevant to affective responding and regulation and to discrimination based on other characteristics, such as physical ability and mental health, should be considered. Perhaps investigating task fMRI response to a social stress task—or a discrimination stress task—would provide greater differentiation of those who are most susceptible to the effects of discrimination.

Another issue is the potentially noncumulative combination of discrimination types. Increased risk for distress syndromes may not simply occur with a higher total number of subtypes of discrimination experienced. Particular subtypes and their specific combinations could be differentially influential and meaningful. For instance, would a combination of sexual orientation discrimination and racial discrimination generate more harm than another combination of two subtypes, such as sexual orientation and body size/shape discrimination? Or would certain subtypes of discrimination confer risk for specific forms of psychopathology or disruptions in specific pathophysiology factors? In a study of suicidality and self-injury in adults with sexual and gender minority identity, the experience of racial/ethnic discrimination amplified responses to stress (4). Perhaps other risk factors are at play. Understanding the role of other forms of adversity, such as financial hardship, maltreatment, family conflict, or neighborhood disadvantage, could elucidate the complexities of challenging social experiences. Similarly, the influence of other forms of psychopathology (e.g., PTSD) or health risk behaviors (e.g., substance use) could amplify associations among discrimination, brain function, and depression.

The development of the self, social cognition, and identity could make adolescents especially vulnerable to the pernicious mental health effects of discrimination. The findings by Grey et al. that discrimination tends to decrease generally across adolescence but also to increase in the years leading into young adulthood provide a picture of changing exposure at a sensitive time, as youths are launching their independent lives. Given that the mediation of adolescent depression by neural response varies based on the timing of exposure to challenging environments such as family financial hardship (5), carefully mapping the pattern of exposure with respect to development could be fruitful. Specifically, studies that can cover broader age ranges, such as by applying accelerated longitudinal designs, could provide information on the influence of discrimination timing.

The authors wisely point out the relevance of their findings for resilience, which is an important direction for future investigations. It will be valuable to examine pathways to resilience or potentially buffering factors that could independently reduce distress outcomes or serve to enhance the engagement of cognitive control processes in those who experience (or are likely to experience) discrimination. Relatedly, it would be helpful to understand the role of treatment, whether with pharmacologic agents intended to address depression and related symptoms or with cognitive-behavioral therapy (CBT) that could improve emotion regulation through strengthening cognitive skills. The authors suggest that the relation between discrimination and distress could reflect a stable trait, and other studies have reported that neural response to affective stimuli can serve a moderating role, combining with discrimination to predict depression and potentially distinguishing those who are vulnerable to the effects of discrimination (6). It will be important to test this hypothesis, along with the optimistic counter-hypothesis that enhanced response in cognitive control regions is amenable to strengthening through experience.

Clinically, we need to identify ways to protect youths from the influence of discrimination, targeting prevention toward those who are most vulnerable (e.g., those with minoritized identities who display lower response in cognitive control systems; those who engage in rumination or self-criticism related to discrimination) and developing strategies focused on key processes, such as cognitive control. Accordingly, CBT interventions for people with minoritized identities may be especially effective when they incorporate techniques designed to strengthen cognitive control aspects of responses to discrimination (e.g., 7, 8).

In tandem with such targeted prevention and intervention efforts, the field of developmental clinical neuroscience will benefit from knowledge about the interplay of factors leading to discrimination-driven disparities. In all—and, ideally, paired with social justice efforts toward reducing structural, community, and interpersonal contributions to discrimination—progress in research and treatment can create a foundation for reducing disparities and promoting thriving in young people.