Abstract
Not much is known about brain structural change in younger populations and minorities. The cross-sectional relationship between depressive symptomatology and racial discrimination with structural measures of brain tissue volume was investigated using magnetic resonance images of 710 participants in the Coronary Artery Risk Development in Young Adults CARDIA Study in 2010. Those reporting depressive symptoms and racial discrimination had lower total brain matter volume compared with those who reported neither (−8.8 mL, 95% confidence interval (CI): −16.4, −1.2), those who reported depressive symptoms only (−10.9 mL, 95% CI: −20.4, −1.4), and those who reported racial discrimination only (−8.6 mL, 95% CI: −16.5, −0.8). Results were similar for total normal white matter. There were 103% higher odds (odds ratio = 2.03, 95% CI: 1.32, 3.14) of being in the highest quartile of white matter hyperintensities in those with depressive symptoms only compared to those without. Although tests for interaction by race were not statistically significant, sensitivity analyses stratified by race revealed inverse associations with total brain matter and total white matter volumes only among black participants with combined depressive symptomatology and experience of racial discrimination, and positive associations only among white participants with depressive symptoms with presence of white matter hyperintensities, suggesting future studies may focus on race.
Keywords: brain physiology, depressive symptomatology, racial discrimination
Depression is a common mental health problem causing significant disability and suffering; an estimated 1 in 10 adults in the United States have depression and 1 in 30 have major depression (1). The etiology of depression is complex, with a multitude of risk factors including psychosocial stress (2), environmental exposures (3), chronic illness and comorbid conditions (4, 5), and family history (6). Magnetic resonance imaging (MRI) has been applied to identify regions of the brain implicated in the pathophysiology of depression, providing insight into the association of depression with structural measures of the brain, though it is uncertain whether structural differences lead to depression or vice versa (7). In previous MRI studies of hospital-recruited subjects with major depressive disorder, pathological cerebral white matter hyperintensities have been found (7, 8). Degradation of white matter integrity has been reported in middle-age onset (9) and late-life onset of major depressive disorder (10). In other studies, gray matter volume abnormalities were seen in subjects with genetic or biological vulnerability to depression (11–14).
There is also a growing scientific interest in exploring the experience of discrimination and its impact on health outcomes (15). Much of the work in the United States has focused on blacks and the association of experiences of racial discrimination with health, although more studies are being conducted in other countries and racial and ethnic groups (16–18). It is apparent that racial discrimination has a negative impact on mental health, though the mechanism is not understood (19). Racial discrimination is related to mood and anxiety disorders and poor well-being in Asian Americans (20, 21). In addition, discrimination related to race has been associated with poor mental health (22), increased substance abuse (23), unfavorable cardiovascular health (24–26), and adverse health outcomes in patients with human immunodeficiency virus or acquired immunodeficiency syndrome (27). Racial discrimination has been characterized as a psychosocial stressor that negatively affects health. Chronic stressors are stronger predictors of onset and course of chronic illness than are acute life events, as shown in the course of breast cancer and irritable bowel syndrome (28, 29). The challenges of measuring chronic stressors have limited a comprehensive assessment of the potential impact of chronic stress on health and health outcomes (30). Conceptually, experiences of racial discrimination are relevant in identifying their contribution to health conditions such as depression, in which onset and progression are characterized by long latency periods. To our knowledge, there have been no studies investigating the relationship between experience of racial discrimination and tissue volumes from brain MRI. Limited data exist as to whether depressive symptomatology and experience of racial discrimination together are associated with physiological changes in brain tissue to a greater extent than the individual components.
In the present study, we explored the cross-sectional relationship among measures of depressive symptomatology; experience of racial discrimination; structural brain tissue volumes, including total brain matter, total gray matter, and total white matter volumes; and abnormal white matter hyperintensities in participants of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, an observational cohort study of cardiovascular risk development in black people and white people. Not much is known about brain structural changes in younger and minority populations. Investigating the relationships between depression and racial discrimination with structural brain measures may lead to an understanding of the ways these forms of stress influence different aspects of brain physiology and function. Given this knowledge gap, the following research questions were addressed in the present study: Is self-reported depressive symptomatology associated cross-sectionally with brain tissue volumes measured by MRI? Do these associations differ by self-reported racial discrimination status? We hypothesized that depressive symptomatology would be associated with lower brain tissue volumes either independently or differing by racial discrimination status.
METHODS
CARDIA Study population and brain MRI substudy
The CARDIA Study’s design and population have been described elsewhere (31). Briefly, young adults, 18–30 years of age at the time of the initial baseline examination in 1985–1986, were recruited for the study. The recruitment goals were to obtain a balanced proportion of black participants (52%) and white participants, men and women (55%), ages (18–24 years, 45%; 25–30 years, 55%), and educational attainment (40% with >12 years of school) at baseline to allow comparisons across these groups both overall and within each field center (Minneapolis, Minnesota; Chicago, Illinois; Birmingham, Alabama; and Oakland, California). Eight follow-up examinations have occurred since baseline from 1987 to 1988 (year 2), 1990 to 1991 (year 5), 1992 to 1993 (year 7), 1995 to 1996 (year 10), 2000 to 2001 (year 15), 2005 to 2006 (year 20), 2010 to 2011 (year 25), and 2015 to 2016 (year 30), collecting a variety of sociodemographic information, psychosocial and physiologic measurements, medical history, and imaging, with 72% retention of the surviving cohort at the year 25 examination.
As part of the ongoing cohort study, 710 participants took part in the brain MRI substudy to the year 25 examination of CARDIA, described in detail elsewhere (32). Brain magnetic resonance images were acquired at 3 of the participating field centers: University of Minnesota (Minneapolis, Minnesota), Kaiser Permanente (Oakland, California), and University of Alabama at Birmingham (Birmingham, Alabama). Exclusion criteria for participation in the ancillary study included participants with a known contraindication to an MRI examination (e.g., severe claustrophobia or implanted metal), any female participant of childbearing age who tested positive on a pregnancy test, or a body size too large for the MRI tube bore.
Brain MRI measurements
For quantitative analyses, 3-Tesla magnetic resonance data were acquired from the following sequences: sagittal 3-dimensional (3D) T1-weighted scan, sagittal 3D T2 fluid-attenuated inversion recovery scan, and sagittal 3D T2-weighted fast spin-echo scan. All scans were monitored during acquisition by an experienced MRI technician and read by a neuroradiologist within 48 hours for clinically relevant findings and graded according to an alert system, with participants notified according to the standardized protocols. Parameters of interest were estimated by analyzing images on the basis of previously described methods (33–36). Brain tissues were classified as gray matter, white matter, and cerebrospinal fluid. Gray and white matter volumes were further characterized into normal and abnormal tissue. Abnormal tissue volumes (or hyperintensities) for gray and white matter were calculated for all regions of interest. Abnormal gray matter volume prevalence was rare and instances were included in normal gray matter volume. From the sagittal 3D T1 sequence, total intracranial volume (a surrogate for head size) was calculated as the sum of gray matter, white matter, and cerebrospinal fluid volumes, and total brain tissue volume was calculated as the sum of gray matter and white matter volumes. Abnormal white matter was estimated from the sagittal 3D fluid-attenuated inversion recovery scan, and T1 and T2 sequences.
Depressive symptomatology
The Center for Epidemiological Studies Depression (CES-D) scale was developed for use in studies of the epidemiology of depressive symptomatology in the general population (37). Symptoms of depression were assessed using the CES-D scale in CARDIA participants at year 25. A 4-point scale is used to indicate how often participants experienced symptoms during the preceding week (0 = rarely or none of the time; 1 = some of the time; 2 = much of the time; 3 = most or all of the time) for 20 items. The CES-D score is the sum of all 20 items of the scale for a total score that ranges from 0 to 60. Scores that are at least 16 are commonly used to indicate depressed mood or dysthymia at the population level. Following this guideline, participants’ CES-D scores were categorized as 0 for scores below 16 and 1 for scores of at least 16 or for participants using antidepressant medications. Following convention used in the CARDIA Study for treated conditions, we included use of antidepressant medication in our definition for depression to capture potentially managed depression with few symptoms.
Experiences of racial discrimination
The Experience of Discrimination Index was used to assess racial discrimination in year 25 (38). Participants were asked, “Have you ever experienced discrimination, been prevented from doing something, or been hassled or made to feel inferior in any of the following seven situations because of your race or color?” Situations included “at school,” “getting a job,” “getting housing,” “at work,” “at home,” “getting medical care,” and “on the street or in a public setting.” Participants were asked to answer yes or no, and if yes, how often: rarely, sometimes, or never. For the cross-sectional analyses, experience of racial discrimination was categorized as any or none for any of the 7 domains.
Demographic variables, physiologic measures, and health behaviors
Covariates used in multivariable analyses were measured in year 25 and included study site (Minneapolis, Birmingham, Oakland); age (continuous; years); race (black or white); sex (female or male); education (continuous; years); employment status (employed or unemployed); marital status (married, marriage-like relationship, single, or other); body mass index (continuous; weight (kg) divided by height (m2)); smoking status (current, former, or never); alcohol intake (continuous; milliliters per day); hypertension based on systolic blood pressure of 140 mmHg, diastolic blood pressure of 90 mmHg, or antihypertensive medication use (yes or no); and diabetes, based on fasting glucose level of at least 126 mg/dL, 2-hour oral glucose tolerance test result of 200 mg/dL or greater, hemoglobin A1c value of 6.5% or greater, or diabetes medication use (yes or no).
Statistical analysis plan
Distributions of variables were graphically assessed, and descriptive statistics (i.e., means, medians, standard deviations, ranges, frequencies, proportions) were calculated for all study variables. Total brain matter, total gray matter, and total white matter volumes were modeled using linear regression, and the additive interaction between depressive symptomatology and racial discrimination was tested cross-sectionally at year 25. Statistically significant interactions were found between depressive symptomatology and experience of racial discrimination in the analyses; therefore, 4 groups of depressive symptomatology and racial discrimination combinations were created for those who had 1) experienced neither depressive symptoms nor racial discrimination, 2) experienced depressive symptoms only, 3) experienced racial discrimination only, or 4) experienced both depressive symptoms and racial discrimination. Adjusted means were then estimated for each of the 4 groups, and differences in means between groups were tested. All models were adjusted for intracranial volume to control for differences in head size. Final multivariate models for the cross-sectional measures of depressive symptoms and discrimination were further adjusted for study site, race, sex, age, alcohol intake, smoking status, education, body mass index, hypertension, diabetes, and intracranial volume measured in year 25.
The distribution of abnormal white matter was highly skewed and consequently dichotomized at 0.6 mL, the 75th percentile for the sample. The binary variable was modeled using logistic regression comparing the odds of the fourth quartile (>0.6 mL) with the first through third quartiles (≤0.6 mL) and tested for statistically significant interactions between depressive symptoms and racial discrimination. Crude and adjusted models contained the same covariates as those described previously. Statistical significance was set at a 2-tailed type-1 error of P < 0.05.
Additional exploratory analyses for all brain outcomes investigated a 2-way interaction between race and racial discrimination, a 2-way interaction between race and depressive symptoms, and a 3-way interaction between race, racial discrimination, and depressive symptoms with brain tissue volumes (data not shown). These interactions were not statistically significant. However, to investigate qualitative differences by race in our main analyses, we conducted sensitivity analyses stratified by race. Sensitivity analyses evaluated the individual associations as well as interactions of depressive symptomatology and racial discrimination similar to those previously described for the total sample.
RESULTS
Of the cohort of study participants who underwent brain MRI, 60% were white, 53% were women, 85% were employed, 60% reported never having smoked, 61% were married or in a married-like relationship, and the mean age was 50.3 years (see Table 1). Table 2 lists crude and adjusted mean values of total volumes each of brain matter, gray matter, and white matter by groups of depressive symptoms and self-reported racial discrimination at year 25 for the total sample. After adjustment, individuals who experienced both depression and racial discrimination at year 25 had statistically significantly less total brain tissue volume (P < 0.05) compared with those who experienced neither depression nor racial discrimination (−8.8 mL; 95% confidence interval (CI): −16.4, −1.2), those who experienced depression only (−10.9 mL; 95% CI: −20.4, −1.4), and those who experienced racial discrimination only (−8.6 mL, 95% CI: −16.5, −0.8). There were no statistical differences among the 3 groups of participants with depression only, racial discrimination only, or with neither. Similarly, participants with depression and experience of racial discrimination had statistically significantly less total white matter volume compared with those with depression only (−11.5 mL; 95% CI: −19.6, −3.4; P < 0.05) and those with racial discrimination only (−7.2 mL; 95% CI: −13.9, −0.5; P < 0.05), and marginally significant less total white matter volume compared with those with neither depression nor racial discrimination (−6.4 mL; 95% CI: −12.9, 0.1; P = 0.055).
Table 1.
Characteristics of Brain Magnetic Resonance Imaging Substudy Participants (n = 710), Coronary Artery Risk Development in Young Adults Study, United States, 2010–2011
| Characteristic | No. | % | Mean (SD) |
|---|---|---|---|
| Elevated depressive symptomatologya | 138 | 19 | |
| Elevated experience of racial discriminationb | 270 | 38 | |
| Black race | 286 | 40 | |
| Female sex | 375 | 53 | |
| Current/former smoker | 281 | 40 | |
| Unemployed | 105 | 15 | |
| Married | 436 | 61 | |
| Age, years | 50.3 (3.5) | ||
| Education, years | 14.9 (2.6) | ||
| Alcohol, mL/dayc | 4.8 (0–400.8) | ||
| Body mass indexd | 28.8 (5.8) | ||
| Hypertension | 207 | 29 | |
| Diabetes | 51 | 7 | |
| Total brain matter volume, mL | 982.4 (106.6) | ||
| Total gray matter volume, mL | 517.0 (53.5) | ||
| Total white matter volume, mL | 465.5 (59.1) | ||
| Intracranial volume, mL | 1,208.4 (133.3) | ||
| White matter hyperintensities, mL | |||
| ≤0.6 | 519 | 73 | |
| >0.6 | 190 | 27 |
Abbreviation: SD, standard deviation.
a Elevated depressive symptomatology defined as a score ≥16 on the Center for Epidemiologic Studies Depression scale or taking antidepressant medication.
b Elevated racial discrimination defined as any or none to all domains of the Experience of Discrimination Index.
c Values presented as median (range).
d Body mass index calculated using the formula: weight (kg)/height (m)2.
Table 2.
Crude and Adjusted Mean Structural Brain Tissue Volumes (mL) for the Total Sample (n = 710) and Stratified by Whites (n = 424) and Blacks (n = 284), Coronary Artery Risk Development in Young Adults Brain Magnetic Resonance Imaging Substudy, United States, 2010–2011a
| Study Sample | No Depressive Symptomatology or Experience of Racial Discriminationb | Depressive Symptomatology Onlyc | Experience of Racial Discrimination Onlyd | Depressive Symptomatology and Experience of Racial Discriminatione | ||||
|---|---|---|---|---|---|---|---|---|
| Mean | 95% CI | Mean | 95% CI | Mean | 95% CI | Mean | 95% CI | |
| Total Sample | ||||||||
| Crude modelsf | ||||||||
| Total brain matter volumeg,h | 983.4 | 980.5, 986.4 | 983.6 | 977.0, 990.2 | 983.9 | 978.0, 987.9 | 974.5 | 967.5, 981.6 |
| Total gray matter volume | 519 | 516.8, 521.3 | 514.5 | 509.5, 519.6 | 516.2 | 513.1, 519.2 | 514.1 | 508.7, 519.5 |
| Total white matter volumeh,i | 464.4 | 461.9, 466.9 | 469.1 | 463.6, 474.6 | 467.8 | 464.4, 471.1 | 460.4 | 454.5, 466.3 |
| Adjusted modelsj | ||||||||
| Total brain matter volumeg,h,i | 984.4 | 981.4, 987.3 | 986.5 | 980.0, 993.0 | 984.2 | 980.1, 988.3 | 974.9 | 968.1, 981.8 |
| Total gray matter volume | 518.6 | 516.3, 520.8 | 515.5 | 510.6, 520.5 | 517.6 | 514.5, 520.7 | 515.8 | 510.6, 521.0 |
| Total white matter volumeg,h,i | 465.8 | 463.3, 468.3 | 470.9 | 465.4, 476.5 | 466.6 | 463.1, 470.1 | 459.1 | 453.3, 464.9 |
| White Participants | ||||||||
| Crude modelsf | ||||||||
| Total brain matter volume | 1,009.4 | 1,006.1, 1,012.7 | 1,009.6 | 1,002.3, 1,016.9 | 1,008.8 | 1,002.0, 1,015.6 | 1,003.8 | 992.9, 1,014.8 |
| Total gray matter volume | 533.2 | 530.8, 535.7 | 530.1 | 524.6, 535.5 | 532.4 | 527.4, 537.5 | 531.4 | 523.2, 539.6 |
| Total white matter volume | 476.3 | 473.5, 479.2 | 479.7 | 473.4, 486.1 | 476.6 | 470.7, 482.5 | 472.6 | 463.1, 482.2 |
| Adjusted modelsj | ||||||||
| Total brain matter volume | 1,008.9 | 1,005.7, 1,012.0 | 1,011 | 1,003.9, 1,018.1 | 1,007.6 | 1,001.0, 1,014.3 | 1,004.5 | 993.8, 1,015.2 |
| Total gray matter volume | 533.1 | 530.7, 535.5 | 531.8 | 526.5, 537.1 | 531.7 | 526.7, 536.7 | 531 | 523.0, 539.0 |
| Total white matter volume | 475.9 | 473.0, 478.8 | 479.3 | 472.9, 485.8 | 476.1 | 470.1, 482.1 | 473.7 | 464.1, 483.3 |
| Black Participants | ||||||||
| Crude modelsf | ||||||||
| Total brain matter volumeg,h | 946 | 939.7, 952.2 | 946.6 | 932.2, 961.0 | 944.9 | 939.8, 949.9 | 932.7 | 923.3, 942.2 |
| Total gray matter volume | 495.4 | 490.5, 500.3 | 486.1 | 474.9, 497.3 | 495.5 | 491.5, 499.4 | 491.6 | 484.2, 498.9 |
| Total white matter volumeg,h,i | 450.5 | 445.7, 455.3 | 460.5 | 449.5, 471.5 | 449.4 | 445.6, 453.3 | 441.2 | 434.0, 448.4 |
| Adjusted modelsj | ||||||||
| Total brain matter volumed | 945.9 | 939.7, 952.1 | 950.7 | 936.4, 965.0 | 946.9 | 942.0, 951.8 | 935.7 | 926.5, 944.9 |
| Total gray matter volume | 496.4 | 491.5, 501.3 | 488.9 | 477.5, 500.3 | 495.2 | 491.3, 499.1 | 493.2 | 485.9, 500.6 |
| Total white matter volumeh,i | 449.5 | 444.7, 454.4 | 461.8 | 450.5, 473.1 | 451.7 | 447.9, 455.6 | 442.4 | 435.2, 449.7 |
Abbreviation: CI, confidence interval.
a Depression defined as a score ≥16 on the Center for Epidemiologic Studies Depression scale or taking antidepressant medications; racial discrimination defined as any or none to all domains of the Experience of Discrimination Index. Estimates are least squares means of brain tissue volumes (mL) and 95% confidence intervals.
b For the total group, n = 367 (51.7%); for whites, n = 278 (65.6%); and for blacks, n = 89 (31.3%).
c For the total group, n = 73 (10.3%); for whites, n = 56 (13.2%); and for blacks, n = 17 (6.0%).
d For the total group, n = 203 (28.6%); for whites, n = 65 (15.3%); and for blacks, n = 138 (48.6%).
e For the total group, n = 65 (9.2%); for whites, n = 25 (5.9%); and for blacks, n = 40 (14.1%).
f Crude models adjusted for intracranial volume.
g Combined depression and racial discrimination compared with none (P < 0.05).
h Combined depressive symptomatology and experience of racial discrimination compared with experience of racial discrimination alone (P < 0.05).
i Combined depressive symptomatology and experience of racial discrimination compared with depressive symptomatology alone (P < 0.05).
j Models adjusted for sex, age, alcohol, smoking status, education, body mass index, hypertension, diabetes, study site, and intracranial volume.
Table 2 lists the findings, by model stratified by race (white and black), of total volumes each of brain matter, gray matter, and white matter relative to depressive symptoms and experiences of discrimination at year 25. Of note, there were no statistically significant differences in brain volumes of white participants between the those with depressive symptoms and those who experienced racial discrimination. However, although the interactions were not statistically significant, the results seen previously for the total sample were similar in the models for black participants. No differences in total gray matter volumes existed for the overall sample or for the race-specific strata.
In the logistic regression model of white matter hyperintensities as a binary variable comparing the fourth quartile with the first through third quartiles, an interaction between depressive symptomatology and racial discrimination was not observed. Therefore, the final model considered depressive symptomatology and racial discrimination independently and reported odds ratios of white matter hyperintensities for elevated versus nonelevated depressive symptomatology and for elevated versus nonelevated experience of racial discrimination, adjusted for each other as appropriate. Participants with depression had 103% higher odds of having abnormal white matter volumes in the highest quartile at year 25 compared with participants in the first through third quartiles after adjustment for racial discrimination and other covariates (odds ratio (OR) = 2.03, 95% CI: 1.32, 3.14). Experiencing racial discrimination was not significantly associated with white matter hyperintensities, after adjusting for depressive symptoms (Table 3). Although sample sizes were small, according to race-specific results, neither depressive symptomatology (OR = 1.65, 95% CI: 0.82, 3.33) nor experience of racial discrimination were statistically significantly associated with white matter hyperintensities in blacks, though there was a positive association with racial discrimination (OR = 1.46, 95% CI: 0.94, 3.47). However, multivariable adjusted models indicated depressive symptoms was statistically significantly associated with white matter hyperintensities in whites (OR = 2.22, 95% CI: 1.26, 3.92), and racial discrimination was inversely associated and not statistically significant (OR = 0.87, 95% CI: 0.48, 1.58).
Table 3.
Odds Ratios of White Matter Hyperintensitiesa for Total Sample (n = 710), and Stratified by Whites (n = 424) and Blacks (n = 284), Coronary Artery Risk Development in Young Adults Brain Magnetic Resonance Imaging Substudy, United States, 2010–2011
| Study Sample | Elevated Depressive Symptomatologyb | Elevated Experience of Racial Discriminationc | ||
|---|---|---|---|---|
| OR | 95% CI | OR | 95% CI | |
| Crude modeld | 2.3 | 1.55, 3.41 | 1.18 | 0.83, 1.68 |
| Adjusted modele | 2.03 | 1.32, 3.14 | 1.24 | 0.82, 1.88 |
| Whites | ||||
| Crude modeld | 2.42 | 1.45, 4.07 | 0.8 | 0.46, 1.40 |
| Adjusted modele | 2.22 | 1.26, 3.92 | 0.87 | 0.48, 1.58 |
| Blacks | ||||
| Crude modeld | 2.26 | 1.22, 4.19 | 1.76 | 0.99, 3.12 |
| Adjusted modele | 1.65 | 0.82, 3.33 | 1.46 | 0.94, 3.47 |
Abbreviations: CI, confidence interval; OR, odds ratio.
a White matter hyperintensities were modeled using logistic regression comparing fourth quartile (≥0.6 mL) to the first through third quartiles (<0.6 mL).
b Depressive symptomatology defined as a score ≥16 on the Center for Epidemiologic Studies Depression scale or taking antidepressant medication.
c Experience of racial discrimination defined as any or none to all domains of the Experience of Discrimination Index.
d Crude models were adjusted for intracranial volume and either depressive symptomatology or experience of racial discrimination, as appropriate.
e Adjusted models were adjusted sex, age, alcohol, smoking status, education, body mass index, hypertension, diabetes, study site, intracranial volume, and either depressive symptomatology or experience of racial discrimination, as appropriate.
DISCUSSION
In the present cross-sectional study, elevated experiences of racial discrimination alone were not associated with global tissue volumes in the brain. We found a positive association between elevated depressive symptomatology and odds of having white matter hyperintensities, a finding consistent with that of other studies of late-life depression (7, 10, 39) and other psychiatric conditions (40). Notably, there were statistically significant cross-sectional differences in brain volumes of participants who reported elevated depressive symptoms and experience of racial discrimination compared with participants who reported having only depressive symptoms, or only experience of racial discrimination, or neither. Specifically, volumes of total brain matter and total white matter were less in those who had both elevated depressive symptoms and elevated experience of racial discrimination compared with those without depressive symptoms and racial discrimination, those with elevated depressive symptoms only, and those with elevated experience of racial discrimination only. To our knowledge, ours is the first study in which the relationships among depressive symptomatology, experience of racial discrimination, and structural MRI of the brain have been examined.
Although there was a lack of a statistically significant interaction among race and depression and racial discrimination, when models were stratified by race, experience of racial discrimination and of depressive symptoms was associated with less brain tissue volumes (i.e., total brain matter and total white matter) in black participants, but not in whites. Conversely, having elevated depressive symptomatology was positively associated with white matter hyperintensities overall, but only in white participants when we examined stratified models. Launer et al. (32), examining the same population, found that smoking and hypertension were associated with greater abnormal white matter volumes, whereas better cognitive function was associated with lesser volumes. However, Bancks et al. (41) found that early markers of cardiovascular health based on the American Heart Association’s Life’s Simple 7 metrics were not associated with abnormal white matter volume 25 years later. Though we cannot exclude the possibility that the associations between race and depressive symptomatology did not differ by racial discrimination status, due to limited power for detection, it may also be true that these differences do indeed exist. Taken together, the qualitative results are intriguing and exploratory, suggesting future studies may focus on race.
There are multiple theories explaining how racism may affect health (16, 24, 30). These theories include differential exposure to determinants of health (e.g., socioeconomic, environmental, behavioral), differential access to and quality of health services, structural levels of racism, and the direct effects of racism, such as trauma and stress (42–44). Experience of racial discrimination alone was not associated with abnormal white matter tissue in our study, though there was a nonsignificant positive association in black participants. In reports from the CARDIA Study, an association has been shown of racial discrimination with adverse cardiovascular outcomes such as high blood pressure (24). It is possible that racial discrimination may lead to high blood pressure or depression and act through other measures, though this was not tested in the present study. Conversely, individuals may learn to live with their conditions and experiences, and compensate accordingly. Such an adaptation to chronic stress does not seem unreasonable.
One of the strengths of data obtained from the CARDIA Study is the standardization across examinations of participant information on medication use and indication, education, alcohol consumption, smoking status, and medical histories. Working within an established large cohort with good retention addresses many of the potential biases that are often issues with smaller studies’ limited representation of variables such as age, education, sex, and race. Because of the exclusion criteria applied to the brain MRI substudy, participants in the substudy tended to have lower BMI values and be healthier than the overall cohort. Therefore, although potentially not generalizable to the entire CARDIA cohort, the findings from the substudy cohort will be conservative in their associations among depression, racial discrimination, and brain MRI. Another strength of the present study is the relatively large number of participants for the brain MRI substudy. Historically, studies of brain MRI were limited to small sample sizes, because the costs of MRI were prohibitive for larger studies. Advances in imaging technologies and wider availability of equipment have greatly reduced costs associated with gathering magnetic resonance images of the brain, and now high-quality images are more widely available (45). As a result, the CARDIA Study had a relatively large sample size for the year 25 brain MRI substudy. This improved the power of statistical tests used in the study, providing confidence in detecting statistically relevant and meaningful associations. Although we were limited to cross-sectional analyses in the present study because these are the first brain MRI data in the CARDIA cohort, follow-up brain MRI is planned for the substudy participants, and these data will provide baseline data to evaluate temporal relationships among depression, racial discrimination, and structural brain MRI in future studies.
The CES-D scale has been validated in several populations (46–48). Similarly, the Experiences of Discrimination Index has been validated in black and Latino populations (38). Social desirability is common when reporting about sensitive topics such as depression or racial discrimination, and participants may have reported responses that are more socially desirable instead of reflecting their true feelings and experiences (49). It is possible individuals may have underreported their depressive symptomatology and experiences of discrimination, which may have attenuated the associations in our study. We were unable to assess the direction or magnitude of bias introduced in our results from social desirability, and this is an accepted limitation of the present study.
In summary, from the breadth of our observational analyses, it appears that the experiences of depressive symptoms and of racial discrimination are related to lower measures of brain tissue volumes in ways that are greater than the contribution of each individual measure. Furthermore, elevated depressive symptomatology appears to be related to the presence of white matter hyperintensities. Although not statistically significant, findings of stratified analyses suggested that the inverse associations between experience of racial discrimination and normal brain volumes were stronger in black participants than in white participants, and white matter abnormalities was directly and more strongly associated with depressive symptoms in white participants than in black participants, whereas experience of racial discrimination was more strongly associated with white matter abnormalities in black participants than in white participants. The planned collection of repeated brain MRI measures will improve assessment of temporality as well as the anatomic basis for the associations of depressive symptoms and experience of racial discrimination with physiologic brain measures.
ACKNOWLEDGMENTS
Author affiliations: Department of Medicine, School of Medicine, University of California, San Francisco, San Francisco, California (Craig S. Meyer); Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Twin Cities, Minnesota (Pamela J. Schreiner); Department of Psychiatry, School of Medicine, University of Minnesota, Twin Cities, Minnesota (Kelvin Lim); University of Pennsylvania Health System, University of Pennsylvania, Philadelphia, Pennsylvania (Harsha Battapady); and the Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland (Lenore J. Launer).
This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005).
Presented at the Annual Meeting of the Society for Epidemiologic Research, June 18–21, 2013, Boston, Massachusetts, and published in abstract form (Am J Epidemiol. 2013;177(11 suppl):S178).
Conflict of interest: none declared.
Abbreviations
- 3D
3-dimensional
- CARDIA
Coronary Artery Risk Development in Young Adults Study
- CES-D
Center for Epidemiologic Studies Depression scale
- CI
confidence interval
- MRI
magnetic resonance imaging
- OR
odds ratio
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