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. Author manuscript; available in PMC: 2026 Feb 13.
Published before final editing as: Clin Psychol Sci. 2026 Feb 11:10.1177/21677026251409754. doi: 10.1177/21677026251409754

Hippocampal Volume Moderates the Link between Racial-Ethnic Discrimination and Early Adolescent Depression

Shanting Chen 1, Beiming Yang 2, Zeix Zhou 3, Teresa Vargas 4, Yichen Wang 5, N Jeanie Santaularia Gomez 6, Emma K Adam 7, Claudia M Haase 8, Yang Qu 9
PMCID: PMC12900041  NIHMSID: NIHMS2128690  PMID: 41693801

Abstract

Adolescent depression has risen sharply, especially among racial-ethnic minority youth. While racial-ethnic discrimination is known to be linked with depression, there is limited understanding of how individual differences in brain development contribute to this process. Drawing on the framework of adolescent neurobiological susceptibility, this study examined the moderating role of hippocampal volume in the longitudinal association between racial-ethnic discrimination and adolescent depression. Using longitudinal data of racial-ethnic minority youth from the Adolescent Brain Cognitive Development study (n = 5,061, Mage = 9.93 years; 52% female), we found that racial-ethnic discrimination was associated with adolescents’ increased depression two years later. Notably, a larger left hippocampal volume amplified the link between discrimination and depression. These findings highlight the detrimental role of racial-ethnic discrimination on adolescents’ psychological well-being and suggest that hippocampal volume may serve as a neurobiological marker of susceptibility, amplifying the negative impact of racialethnic discrimination among racial-ethnic minority youth.

Keywords: racial-ethnic discrimination, hippocampal volume, racial-ethnic minority youth, depression

Racial-ethnic minority youth in the United States (e.g., Black, Latinx, Asian American) face an elevated risk of developing depression and encounter greater challenges accessing essential mental health services compared to their White counterparts (Weersing et al., 2022; Wilson & Dumornay, 2022). Recognizing and addressing the racially and ethnically salient stressors contributing to these disparities is crucial for designing targeted interventions aimed at improving the mental health outcomes of racial-ethnic minority youth. One important contributor to depression among racial-ethnic minority youth is their experience of racial-ethnic discrimination, which is defined as unfair treatment of individuals based on race and ethnicity (Benner et al., 2018). It is well established that racial-ethnic minority youth frequently experience discriminatory treatment, which becomes a pervasive source of stress in their daily lives (Fisher et al., 2000). At the same time, not everyone is affected in the same way – some youth are particularly susceptible to the harmful effects of racial-ethnic discrimination whereas others are less affected. According to the neurobiological susceptibility model (Schriber & Guyer, 2016), adolescents with different brain structures and functions may react to social experiences differently. Therefore, it is important to examine the potential neurological marker of susceptibility to identify who are more vulnerable to racial-ethnic discrimination. To fill this gap in the literature, the current study aims to examine the moderating role of hippocampal volume, a critical bran region involved in depression and sensitivity to social context (Barch et al., 2019; Schriber et al., 2017), in the link between racial-ethnic discrimination and adolescent depression, using longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study.

Racial-Ethnic Discrimination among Racial-Ethnic Minority Youth

Racism has interpersonal, institutional, structural and cultural dimensions. In interpersonal contexts, individuals from minoritized backgrounds can experience racial-ethnic discrimination as prejudgment, bias or discrimination based on their race or ethnicity (Benner et al., 2018). In 2021, the Centers for Disease Control and Prevention officially recognized racism as a public health threat due to its significant role in perpetuating health disparities among racial-ethnic minorities (CDC, 2021). Racial-ethnic discrimination is consistently found to be associated with diminished self-esteem, more depressive and anxiety symptoms, and other indicators of mental health and psychological well-being (Benner et al., 2018; Schmitt et al., 2014; Williams et al., 2019). Adolescence, a critical developmental period, offers a key window to examine the impact of racial-ethnic discrimination. During this phase, adolescents undergo rapid cognitive growth and become highly sensitive to social evaluation, particularly negative or hostile evaluations related to their identities, yet often lack effective coping strategies (Spencer, 2007). This vulnerability may heighten the detrimental effects of discrimination. Indeed, studies have found that the adverse effects of discrimination for children and adolescents are stronger compared to those for adults (Schmitt et al., 2014). Empirical studies have consistently confirmed the negative impacts of racial-ethnic discrimination on racial-ethnic minority youth’s mental health, with research showing that racial-ethnic discrimination experiences were strongly linked to depressive symptoms (Benner et al., 2018; Chen & Mallory, 2021).

The Moderating Role of Hippocampal Volume

Although racial-ethnic discrimination is clearly detrimental to health, not all adolescents are equally susceptible to its negative influence. The environmental sensitivity framework (Pluess, 2015) posits that individuals differ in their responsiveness to environmental influences due to variations in how they perceive and process contextual information. Building upon this framework, the neurobiological susceptibility model (Schriber & Guyer, 2016) emphasizes that individual’s sensitivity to social experiences (e.g., racial-ethnic discrimination) may vary based on their neurobiological factors (e.g., brain characteristics structure and function). This perspective aligns with the “orchid-dandelion” metaphor (Belsky, 2016), which suggests that some individuals are “orchid-like”, exhibiting heightened sensitivity to both supportive and adverse environments, while others are more “dandelion-like”, demonstrating relative resilience regardless of context. However, the specific neurobiological factors that may confer heightened susceptibility to the psychological consequences of racial-ethnic discrimination remain underexplored. Identifying the potential neurological factors are critical to advancing our understanding of why some adolescents are more vulnerable to discrimination-related mental health risks than others. Adolescent may be a particularly pivotal period for examining the interactive effects of the brain and social context because it is a period marked by significant brain development, heightened sensitive to social contexts, and an increased risk for the onset of psychopathology (Paus et al., 2008).

The hippocampus is a critical brain region involved in the development of depression across the life span (Barch et al., 2019) and is known to be sensitive to social stressors (Larosa & Wong, 2022). It may serve as a neurobiological marker of susceptibility, shaping adolescents’ psychological responses to racial-ethnic discrimination and contributing to risk for psychopathology for the following reasons. First, the hippocampus plays a central role in social-context sensitivity, a mechanism that may underlie its contribution to the development of depression during adolescents (Schriber & Guyer, 2016). It is essential for a wide range of cognitive and emotional functions (e.g., perceptions, imagination, emotional processing). More specifically, the hippocampus is important for connecting contextual and emotional aspects of experience, form and recall memories, and distinguish between threats and safety (Britton et al., 2011; Rolls, 2018). Given these functions, a larger hippocampus may heighten adolescents’ vigilance toward discriminatory treatment and enhance the encoding and retention of these negative experiences in memory—potentially increasing their emotional impact and contributing to long-term psychological consequences. Second, the hippocampus is involved in regulating the body’s stress response due to its high concentration of glucocorticoid receptors, which allow it to detect circulating stress hormones (Jankord & Herman, 2008). Through these receptors, the hippocampus plays a key role in regulating activities in the hypothalamic-pituitary-adrenal (HPA) axis, the body’s main stress response system, making it particularly sensitive to contextual stressors, including racial-ethnic discrimination.

However, much of the existing work focused on examining the link between racial-ethnic discrimination on the size of hippocampus volume. Specifically, studies have found that Black and Latino youth living in high structural stigma environments exhibit smaller hippocampal volumes compared to those in lower stigma contexts (Hatzenbuehler, 2021). Similarly, another study found longitudinal association between racial-ethnic discrimination and smaller hippocampal volume among black older adults (Zahodne et al., 2023). However, in line with the neurobiological susceptibility model (Schriber & Guyer, 2016), it is also important to examine whether, and to what extent, the hippocampus serves as a neurobiological marker of susceptibility, rendering individuals more or less susceptible to the negative effects of racial-ethnic discrimination on depression, a question that remains largely unexplored. Given the scarcity of research specifically examining the moderating effect of hippocampal volume on the relationship between discrimination and mental health outcomes, we draw on related studies focused on other forms of contextual stress to inform our hypotheses. Notably, one study found that Mexican-origin adolescents with larger hippocampal volume, compared to those with smaller volumes, showed heightened levels of depressive symptoms when exposed to stressful environment (e.g., community crime (Schriber et al., 2017). Similarly, in another study, larger hippocampal volume among adolescent girls were linked to heightened sensitivity to the harmful effects of maternal aggression on changes in depressive symptoms during early to mid-adolescence (Whittle et al., 2011). Another recent study using the ABCD longitudinal dataset found similar patterns, showing that a larger left hippocampal volume heightened adolescents’ sensitivity to negative social contexts (e.g., peer victimization and family conflicts; Martinez et al., 2024). These findings collectively suggest that greater hippocampal volume during adolescence may be a marker of increased susceptibility to adverse social environments, particularly in relation to the development of depressive symptoms.

There may be lateral differences with regard to the role of hippocampal volume in the link between racial-ethnic discrimination and adolescent depression. For instance, Schriber et al. (2017) found that a larger left, but not right, hippocampal volume intensified sensitivity to community crime as a risk factor associated with depressive symptoms. The left hippocampus has been suggested to be heavily involved in language processing and autobiographical memory, aiding in integrating contextual memories (Burgess, 2002; Iglói et al., 2010). Consequently, adolescents with larger left hippocampal volume may experience increased levels of depression following discrimination. Therefore, it is possible that adolescents with larger left, but not right, hippocampal volume might have heightened sensitivity in their depressive symptoms in the face of racial-ethnic discrimination. According to multiple studies, the effects of hippocampal volume are typically lateralized and mainly manifest in the left hemisphere.

Current study

Using longitudinal data from the ABCD study, the current study aimed to examine the following research questions. First, the current study examined whether racial-ethnic discrimination was associated with increased depression over time among racial-ethnic minoritized early adolescents. We hypothesized that youth who experienced racial-ethnic discrimination in early adolescence would exhibit increased levels of depression. Second, the current study explored whether hippocampal volume would moderate the association between racial-ethnic discrimination and adolescent depression. Drawing upon the framework of adolescent neurobiological susceptibility to social context (Schriber & Guyer, 2016) and prior empirical research (Schriber et al., 2017), it was hypothesized that individuals with larger hippocampal volume would exhibit a stronger link between racial-ethnic discrimination and depression, while this association would be weaker for those with smaller hippocampal volume. Lastly, the current study examined the potential lateral effects within the hippocampus. Given the known lateralization of hippocampal functions, we hypothesized that the moderating effect would be more evident in the left hippocampus than in the right hippocampus.

Methods

Participants

Data were obtained from baseline (T1), one-year follow-up (T2), and two-year follow-up (T3) of the ongoing Adolescent Brain Cognitive Development Study (data release 4.0). All the data included in the current study are available on the NIMH Data Archive (https://nda.nih.gov/abcd). The ABCD study is a massive multi-site that currently examines approximately 11,876 youth aged from 9–10 years in the baseline sample (Karcher & Barch, 2021). A flow diagram of subjects included or excluded from analyses was provided in Figure S1. Racial-ethnic categories to determine inclusion in the analysis were defined from the parent-reported demographics survey at baseline with the race_ethnicity variable (i.e., Asian, Black, Hispanic, Other, White), and all categories other than White were included. Among this sample, 633 participants were excluded based on the quality control criteria of MRI in ABCD data release note 4.0 (for detailed criteria, see ABCD Human Subjects Study, 2021), resulting in a final analytical sample of 5,061: 44% Latinx (n = 2,227), 30% non-Hispanic Black (n = 1,518), 22% Others (n = 1,113), and 5% non-Hispanic Asian (n = 253); 50% female (n = 2530); Mage = 9.93 years, SD = 0.62 at T1). For the “Others” group, the majority of participants were multiracial or multiethnic (83%), while the remaining participants were Native American/Alaskan Native (3%), Native Hawaiian or Other Pacific Islander (1%), or endorsed “Other” (13%). The median parental education level was finished some college. Detailed demographics of the analytical sample can be found in Table S1, with demographics for each racial-ethnic group presented in Table S5.

Transparency and Openness

Preregistration.

We preregistered the study at https://aspredicted.org/1WQ_DZL.

Data, materials, code, and online resources.

This study involved analyses of an existing dataset, ABCD Study Data Release (4.0). The selected data are available from the authors on request; for the analysis code, see the Supplemental Material available online.

Ethical approval.

A centralized Institutional Review Board (IRB) approval was obtained from the University of California, San Diego, and study sites also obtained approval from their local IRBs. Informed assent and consent were obtained from the participating youth and their parents or guardians, respectively.

Reporting.

We reported all data-preprocessing steps, including how we arrived at the final analytical sample and the inclusion/exclusion criteria. We also described the sample characteristics and provided detailed information on the measurement scales used in the analyses. Data were cleaned and analyzed using R (Version 4.5).

Magnetic resonance imaging data acquisition

At T1, all participating children in the ABCD study completed a high-resolution T1-weighted structural MRI scan (1-mm isotropic voxels) with any of the following scanners: Philips Healthcare (Andover, Massachusetts), GE Healthcare (Waukesha, Wisconsin), or Simens Healthcare (Erlangen, Germany). All the structural MRI data were processed using FreeSurfer version 5.3.0, in line with the standard processing pipelines. The process included the removal of nonbrain tissue, the segmentation of gray and white matter, and the parcellation of the cortical and subcortical structures. Every scan session underwent a radiological review. An extended quality control protocol was implemented, which included a visual inspection of T1 images and FreeSurfer outputs for an acceptable quality. Any MRI imaging that did not pass the quality control was excluded. Regions of interest in this study were the right and left hippocampus. These data were extracted from T1-weighted MPRAGE images that had been visually inspected by trained technicians and preprocessed using the ABCD pipeline, which included gradient distortion correction, intensity inhomogeneity correction, registration to standard space, and motion correction (Hagler et al., 2019). Subcortical segmentation of the hippocampus was completed using FreeSurfer v5.3 and an automated, atlas-based segmentation process. The ABCD imaging modalities and processing procedures are well described elsewhere (Hagler et al., 2019). We separately computed the ratio between the left- and right-hippocampal volumes to intracranial volume.

Questionnaire Measures

In ABCD study, racial-ethnic discrimination was first administered at T2 and thus T2 racial-ethnic discrimination was used in the current study. Depressive symptoms were assessed at both T1 and T3, and covariates were measured at T1.

Racial-ethnic discrimination.

Adolescents reported on seven-item measure assessing experiences of racial-ethnic discrimination over the past 12 months (dim_y_ss_mean). Three items asked how often they were treated unfairly because of their ethnic background by “teachers,” “other adults outside school,” and “other students.” Additional items included statements such as “I don’t feel accepted by other Americans” and “I feel that others behave in an unfair or negative way toward my ethnic group.” Responses ranged from 1 (almost never) to 5 (very often), with higher scores indicating greater perceived discrimination. The measure demonstrated good internal consistency (α = .75), and a mean score was calculated across all items.

Youth’s depressive symptoms.

At both T1 and T3, the Kiddie Schedule for Affective Disorders and Schizophrenia for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5; KSADS-5) was utilized to measure endorsement for depressive symptoms, and prompts for the presence of 22 symptoms of irritability, anhedonia, insomnia, fatigue, trouble concentrating, indecision, altered appetite, altered appetite, altered psychomotor presentation, guilt, hopelessness, lowered self-esteem, self-harm, suicidality, and change in functioning related to those symptoms. Following previous studies (Vargas & Mittal, 2021), a sum score was created to indicate the total number of items endorsed. The KSADS-5 has been established as a valid and reliable measure of psychopathology in children and adolescents. This measure showed good internal consistency (α = .86 at both T1 and T3).

Demographic covariates.

Following prior studies using the ABCD dataset (e.g., Yang et al., 2023), the current study controlled for youth’s age, biological sex, race/ethnicity, household financial adversity, parent’s marital status and parents’ history of depression, which were measured at T1. Biological sex was coded into 0 = male and 1 = female. Nativity was coded into 0 = U.S. born and 1 = foreign born. Raceethnicity was coded into four binary variables: non-Hispanic Black, non-Hispanic Latinx, non-Hispanic Asian, and other races (including multiracial). Latinx was used as the reference category due to its being the largest subgroup in the sample. Household financial adversity was the sum score of seven items on experiences of financial difficulties in the past 12 months (0 = no and 1 = yes) reported by the primary caregiver of the youth. Parents’ marital status was coded into 0 = not married or living together with a partner and 1 = married or living together with a partner. Family history of depression. Parents’ history of depression was coded as 0 = no and 1 = yes.

Analytical plan

Analyses were conducted using mixed-effect models from the lme4 package in R version 4.0.2. For multilevel models, participants’ site and family were included as random intercepts, demographic variables were included as fixed-effect covariates, and family and study sites were random effects because subjects were nested to families that were nested to study sites. The attrition rate from T1 to T2 was approximately 11% and from T2 to T3 was around 7%. Results in Little’s test (χ2 = 297.19, p < .001) suggested that missing cases were not missing completely at random (MCAR; Little, 1988). Multiple imputation was employed to address the missing data using Blimp (Keller & Enders, 2023). Specifically, a fully conditional specification multiple imputation (FCS-MI) approach was used and 50 imputed data sets were created (Graham et al., 2007). In addition, analyses using listwise deletion were also included as Supplementary Analyses section to ensure the robustness of the results.

There are two sets of analysis. In the first set of analyses, youth’s depressive symptoms at T3 were positively linked with racial-ethnic discrimination at T2, controlling for youth’s depressive symptoms at T1 and demographic covariates. Then, the second set of analyses was conducted to test the moderation effect of the youth’s left and right hippocampal volume (T1) on the association between racial-ethnic discrimination (T2) and depressive symptoms (T3), also controlling for youth’s depressive symptoms at T1 and demographic covariates. In the second set of analysis, the predictor and moderators were mean-centered. The interaction effects were probed using the simple slope technique (Bauer & Curran, 2005), which estimates and presents the associations between racial-ethnic discrimination and adolescents’ depression with a low level (i.e. 1 SD below the mean) and a high level (1 SD above the mean) of left and right hippocampal volume. We also used the Johnson-Neyman technique (Johnson & Fay, 1950) in R 4.5 to determine at which point on the hippocampal volume spectrum the effect of racial-ethnic discrimination on depression became significant or non-significant.

Results

Table S2 shows the correlations between key variables examined in the current study. Racial-ethnic discrimination was significantly correlated with higher levels of depressive symptoms at T3 (r = .09, p < .01) and smaller hippocampal volume (left: r = −.04, p < .01; right: r = −.05, p < .01). The first set of analyses examined whether youth’s depressive symptoms at T3 were linked with racial-ethnic discrimination at T2. As shown in Model 1 of Table 1, there was a significant main effect of racial-ethnic discrimination on adolescents’ depressive symptoms (b = .08, p < .001). Specifically, racial-ethnic discrimination at T2 was associated with increased depressive symptoms among racial-ethnic adolescents at T3, adjusting for depressive symptoms at T1 and demographic covariates.

Table 1.

Moderation effects of hippocampal volume on the link between racial-ethnic discrimination and depressive symptoms

Model 1 Model 2
b (SE) p value b (SE) p value
Racial-ethnic discrimination 0.18 (0.05) 0.00 0.19 (0.05) 0.00
Left hipp (mm3/ICV × 1,000) 0.31 (0.15) 0.03 0.29 (0.15) 0.05
Right hipp (mm3/ICV × 1,000) −0.15 (0.13) 0.26 −0.15 (0.13) 0.25
Prior depressive symptoms 0.14 (0.01) 0.00 0.14 (0.01) 0.00
Nativity −0.07 (0.09) 0.48 −0.09 (0.09) 0.31
Age 0 (0) 0.18 0 (0) 0.19
Sex −0.22 (0.04) 0.00 −0.23 (0.04) 0.00
Family financial adversity 0.05 (0.02) 0.00 0.05 (0.02) 0.00
Parents’ marital status −0.08 (0.04) 0.07 −0.09 (0.04) 0.03
Parents’ history of depression 0.06 (0.06) 0.32 0.06 (0.06) 0.31
Black 0.03 (0.05) 0.56 0.03 (0.05) 0.56
Asian −0.13 (0.1) 0.19 −0.14 (0.1) 0.15
Other 0.02 (0.05) 0.70 0.02 (0.05) 0.66
Discrim * Left hipp - - 0.64 (0.32) 0.04
Discrim * Right hipp - - −0.56 (0.33) 0.10
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Note: hipp = hippocampus volume. Significant results are in bold.

The second set of analyses examined whether hippocampal volume measured in early adolescence moderated the longitudinal association between racial-ethnic discrimination and youth’s depressive symptoms. Results showed left, but not right, hippocampal volume moderated the link between racial-ethnic discrimination and depressive symptoms (Model 2 of Table 1). As shown in Figure 1a, adolescents with larger left hippocampal volume exhibited a stronger association between racial-ethnic discrimination and depression (b = .10, p < .001), whereas this association was weaker for those with smaller left hippocampal volume (b = .06, p < .01). However, the right hippocampal volume did not moderate such link. These results suggested that, with regard to their depressive outcomes, adolescents with larger left hippocampal volume were more sensitive to the negative effects of racial-ethnic discrimination compared to those with smaller left hippocampal volume. Based on the Johnson-Neyman technique (Figure 1b), the positive link between racial-ethnic discrimination on depression became significant when the hippocampal volume was above −0.12 (standardized unit, 69% of sample).

Figure 1.

Figure 1.

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Simple slope analyses and Johnson-Neyman plots of significant interaction effects

Sensitivity Analyses

To examine the robustness of the results, all the models were analyzed again using listwise deletion (Table S3). No meaningful changes in results were found. More specifically, racial-ethnic discrimination was linked with increased depressive symptoms over time (b = .18, p <.001), adjusting for prior depressive symptoms and demographic covariates. Moderation results remained the same as well. Specifically, left hippocampal volume moderated the longitudinal associations between racial-ethnic discrimination and depressive symptoms (b = .59, p = .02). The simple slopes analyses showed the similar pattern that greater racial-ethnic discrimination was linked with greater depressive symptoms over time when left hippocampal volume is large (b = .32, p < .001) but did not when the when left hippocampal volume is small (b = .05, p = .54).

In rule out the possibility of hippocampal volume being a state marker of depressive symptoms, we examined the concurrent associations between depressive symptoms and hippocampal volume at baseline (Table S4). The results showed that neither left nor right hippocampal volume was associated with depressive symptoms (i.e., both p values > .20), making it unlikely an interpretation for the left or right hippocampal volume as a marker of depressive states.

To explore the potential bidirectional relationship between racial-ethnic discrimination and depressive symptoms—specifically, the possibility that youth experiencing greater depressive symptoms may be more sensitive to perceiving discrimination (Ong et al., 2013)—we conducted additional analyses using depressive symptoms at Time 1 to predict racial-ethnic discrimination at Time 2. The results revealed a significant positive association (b = .05, p < .001), indicating that adolescents with higher levels of depressive symptoms were more likely to report higher levels of perceived racial-ethnic discrimination over time (Table S4). These findings suggest that the relationship between discrimination and depression may be bidirectional.

Discussion

Guided by the environmental sensitivity framework (Pluess, 2015) and adolescent neurobiological susceptibility framework (Schriber & Guyer, 2016), the present study examined the interplay between social-contextual exposure (i.e., racial-ethnic discrimination) and a neurobiological factor (i.e., hippocampal volume) in shaping racial-ethnic minority youth’s depression during early adolescence. Specifically, the aims of this study were: (1) to determine if racial-ethnic discrimination was associated with increased depression among racial-ethnic minoritized early adolescents; (2) to assess if this association was moderated by hippocampal volume; and (3) to assess laterality effects within the hippocampus. Our findings suggest that adolescents who experienced more racial-ethnic discrimination exhibited elevated depressive symptoms. In addition, our results found that those with larger left hippocampal volume were more vulnerable to the negative impact of racial-ethnic discrimination on changes in depressive symptoms over time. These findings highlight the hippocampus as a key brain region for understanding individual differences in vulnerability to discrimination-related stress and depressive outcomes.

The current study documented the detrimental effects of racial-ethnic discrimination on depressive symptoms using a large-scale longitudinal sample of Latinx, Black, Asian, and mixed-race adolescents in the U.S. Specifically, a 1 SD increase in racial-ethnic discrimination was linked with a .08 SD increase in depressive symptoms over time, controlling for a wide variety of covariates including youth’s age, sex, parents’ educational attainment and family financial adversity. Our results is consistent with empirical findings across many scientific disciplines, including psychology (e.g., Rogers et al., 2021), public health and sociology (e.g., Williams et al., 2019), as well as health disparity research (Alvidrez & Barksdale, 2022). Results from the current study provide some of the first large-scale evidence that racial-ethnic discrimination is significantly linked with poorer mental health outcomes in early adolescence, thus extending earlier smaller-scale work by Benner and colleagues (2018) and suggesting further probing of early adolescence as a critical developmental period for the detrimental effects of racial-ethnic discrimination.

Our sensitivity analyses also provided evidence supporting the potential bidirectional relationship between racial-ethnic discrimination and depressive symptoms, with findings indicating that adolescents’ depressive symptoms at T1 was significantly linked with higher reports of discrimination at the following wave (T2). This aligns with prior research showing that daily fluctuations in negative affect can predict the subsequent perception of racial microaggressions (e.g., Ong et al., 2013). These findings underscore the need for future research to move beyond unidirectional models and more rigorously examine reciprocal dynamics between discrimination and mental health. Longitudinal and experience-sampling designs will be particularly valuable in disentangling how depressive symptoms may both result from and contribute to heightened sensitivity to discriminatory experiences over time.

Substantial heterogeneity in the link between racial-ethnic discrimination and depressive symptoms has long sparked interest in what factors buffer or amplify the effects (e.g., Jolicoeur-Martineau et al., 2020). Our findings indicate that left hippocampal volume moderates the association between racial-ethnic discrimination and depression in early adolescence. Specifically, adolescents with larger hippocampal volumes exhibit a stronger association between experiences of racial-ethnic discrimination and depressive symptoms, whereas those with smaller volumes—particularly those below −0.12 in standardized units—appear relatively less affected. These findings align with Schriber et al. (2017) and Whittle et al. (2011)’s studies, which suggested that hippocampal volume’s role as a marker of susceptibility to social contexts. Our findings are supported by the social brain theory (Dunbar, 2009), indicating that a larger hippocampus may enhance brain’s processing of racial-ethnic discrimination experiences, increasing vulnerability among early adolescents. Moreover, another explanation is that larger hippocampus may intensify stress perception and emotional regulation challenges, given the hippocampus’s key role in these areas (Larosa & Wong, 2022; Zhu et al., 2019). Future studies should further investigate the mechanisms of the susceptibility role of hippocampal volume. For example, racial-ethnic discrimination has been found to be related to depressive symptoms through acculturative stress (Lorenzo-Blanco & Unger, 2015), or anger regulation (Park et al., 2017). Understanding whether these youth perceive greater stress or exhibit stronger emotional responses, such as anger, can inform targeted interventions. Identifying such neurobiological profiles may help clinicians and school mental health professionals deliver more effective prevention and coping-skills training, especially in high-risk social contexts. This underscores the importance of integrating neurobiological markers into assessments of risk and resilience among marginalized youth.

Strengths, Limitations, and Future Directions

Overall, our study lends support to neurobiological susceptibility models (Ellis et al., 2011; Schriber & Guyer, 2016), and advances it by identifying the social susceptibility by using a brain-related measurement. Our study also enhances understanding of racial-ethnic discrimination and adolescent depression by finding the amplifying role of hippocampal volume for the negative effect of racial-ethnic discrimination on adolescent depression. The results highlight the need to consider brain development when investigating susceptibility to racial-ethnic discrimination and provided a framework for future research on additional neural markers that may confer vulnerability to racial-ethnic discrimination.

Despite these strengths, there are also a few limitations. First, the present study zoomed in on interpersonal racial-ethnic discrimination. Future research is needed to probe effects of structural, cultural, and other forms of racism on depressive symptoms and other mental health outcomes. Second, the dynamic nature of hippocampal volume and depression requires further investigation. Our study used baseline level of hippocampal volume since we treated it as a stable individual difference factor. However, as hippocampal volume evolves throughout adolescence and is shaped by life experiences such as stress (Gogtay et al., 2006; Pruessner et al., 2005). For example, Chan et al. (2016) discovered that smaller hippocampal volume observed in adulthood might reflect a delayed scarring effect from earlier depression, whereas a larger hippocampal volume could signify resilience, offering protection to individuals at high risk of depression. Consequently, future studies should explore the influence of hippocampal volume on susceptibility across various age groups. Third, our focus on early adolescence (age 10–12) limits the generalizability of our findings to other developmental stages such as late adolescence, childhood, or adulthood. Future studies could use future released data in the ABCD study to validate our model in different adolescent phases and throughout the lifespan. Fourth, while we focused on the overall volume of the hippocampus, it is important to consider that other brain regions may also serve as neurobiological susceptibility markers. It remains to be explored whether specific subregions of hippocampus or other relevant brain areas might differentially moderate the link between racial-ethnic discrimination and depression. Fifth, our study did not account for the nuanced differences in experiences of racial-ethnic discrimination across specific subgroups. For instance, Black, Latinx, Asian, and multiracial youth may face distinct forms and sources of discrimination shaped by sociocultural and historical contexts. Additionally, there is considerable variability within these groups in how discrimination is experienced (Findling et al., 2019). Future research should aim to unpack these subgroup differences to better understand how the type, frequency, and impact of racial-ethnic discrimination may differentially influence adolescent development and neurobiological susceptibility. Lastly, although our study used longitudinal data, it captured only a limited period of adolescents’ development. It is possible that some individuals experienced and reported discrimination prior to the baseline assessment, which could have already influenced their psychological well-being. Therefore, we cannot draw causal conclusions from the current findings.

Conclusion

Adolescence is a crucial developmental stage marked by the emergence of major depressive disorder, during which adolescents face social stressors and undergo significant biological and social changes. The current study echoes the literature by highlighting the lasting harmful impacts of racial-ethnic discrimination on racial-ethnic minority youth’s depression. Our results highlight the importance for schools and teachers to implement zero-tolerance policies around discrimination within schools and classrooms. It also underscores the importance of supporting early adolescents’ mental health as a way to potentially reduce heightened perceptions of racial-ethnic discrimination in this population. In addition, our study also contributes to the literature by demonstrating that left hippocampal volume exacerbates the longitudinal relationship between racial-ethnic discrimination and depression in early adolescence. Our findings identify a tangible neural risk factor for developing depression in early adolescents following exposure to racial-ethnic discrimination. Specifically, early adolescents with larger left hippocampal volume are more vulnerable to the harmful effects of racial-ethnic discrimination on depression, compared to their counterparts with smaller left hippocampal volume. This suggests that interventions on improving racial-ethnic minority youth’s mental health should avoid one-size-fits-all approach. Instead, it is important to customize the content based on individual neurobiological characteristics. Overall, the study underscores the urgent need to combat racial-ethnic discrimination and the necessity of informing future policies and interventions to provide greater support to youth who are more vulnerable to the negative impact of racial-ethnic discrimination.

Supplementary Material

Supplementary_Material

Acknowledgement

The ABCD Study® was supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123 and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners. html. This research was supported by the National Science Foundation (BCS-1944644) and research fund from the Center for Culture, Brain, Biology, and Learning at Northwestern University.

Contributor Information

Shanting Chen, Department of Psychology, University of Florida, U.S.A..

Beiming Yang, School of Education and Social Policy, Northwestern University.

Zeix Zhou, Human Development and Family Science, University of Texas at Austin.

Teresa Vargas, Department of Psychology, Harvard University.

Yichen Wang, Department of Psychology, Cornell University.

N. Jeanie Santaularia Gomez, Department of Epidemiology, University of Washington.

Emma K. Adam, School of Education and Social Policy, Northwestern University

Claudia M. Haase, School of Education and Social Policy, Northwestern University

Yang Qu, School of Education and Social Policy, Northwestern University.

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