Introduction to the Special Issue

INTRODUCTION For decades, community studies have revealed variations in psychopathology across social groups when stratified according to socioeconomic status, ethnicity, race, gender identity, sexual orientation, and physical disability. These variations include differences in disorder prevalence, symptom expression, illness severity, coping and resilience, and the models by which people understand illness, treatment, and recovery. The evidence base describing these variations continues to expand, but the reasons for such variations remain underspecified. Certain intergroup differences are clearly associated with oppressive societal forces such as structural racism, sexism, homophobia, transphobia, and poverty. These forces distribute vulnerabilities and coping resources differentially across individuals and social groups, predisposing them to the uneven emergence and persistence of psychopathology. They include variations in exposure to violence or unfair imprisonment; access to education or employment; and the effects of discriminatory organizational practices, such as racist hiring processes or differential pay by gender. These societal forces also present barriers to care that introduce inequities for certain groups across the entire help-seeking pathway. For instance, particular social groups may encounter difficulties accessing mental health care; receiving evidence-based, guideline-concordant treatments; continuing services through appointments and treatment adherence; and attaining symptom remission, improved quality of life, and decreased mental health-related disabilities. The articles in this special issue of the Harvard Review of Psychiatry come from presentations given at the 2024 annual meeting of the American Psychopathological Association that aimed to identify research gaps on mechanisms that interact across social-structural, cultural, psychological, and biological levels to create and sustain inequities. By mechanism, we mean a hypothesized causal relationship that could modify the outcome of any disorder at the biological, psychological, or social levels.1 Delineating levels beyond the biological is a critique of biomedical reductionism that prioritizes neuroscience over other scientific paradigms2 and an affirmation that the psychological, social, and cultural are essential domains that situate illnesses in everyday life.3 The notion of interaction recognizes that these dimensions are too often considered in isolation but can be integrated in multilevel explanatory frameworks.4 Inequities refer to differences among social groups that result from overt discrimination, whether historical or contemporary.5 The authors in this special issue seek interventions that go beyond rate descriptions or inequity trends. Instead, they posit mechanisms that could inform scientific research, government policies, and clinical practices. Any discussion about mechanisms across social-structural, cultural, psychological, and biological levels forces definition of these terms. Aggarwal6 addresses this point by analyzing frameworks for cultural factors, social structures, and social determinants of health. Cultural psychiatrists and medical social scientists have debated whether structural competence7 or cultural competence8 should be emphasized in clinical case formulations. Advocates of structural competence contend that clinical cultural competence interventions too often foreground individual patient beliefs and behaviors without considering political, economic, and geographic determinants of health.7 Advocates of cultural competence counter that clinicians should not discount rich scholarship on cultural competence that spans five decades because social and cultural variables can be integrated.8 Aggarwal examines the various sides in this debate to make the broader point that researchers and professional practice organizations, such as the American Psychiatric Association and American Psychological Association, have fundamentally different understandings of these frameworks. Based on experience with cultural competence interventions, such lack of clarity could dissuade clinicians from incorporating frameworks for structural factors or social determinants of health if they are poorly defined and lack usable tools. Aggarwal concludes with several calls for involving clinicians, researchers, and policymakers in devising workable definitions for social determinants and social structures, domains for assessment, and tools for their implementation. One contribution makes the case for applying these frameworks by identifying intellectual traditions that more precisely define such constructs. Margarita Alegría and colleagues9 recommend that racial and ethnic inequities in mental health should be examined through the social determinants of health framework. Beyond simple demographic affiliation, they underscore, “It is also important to acknowledge that experiences with race can shape an individual’s environment and social circumstances [original emphasis].” Recognizing that social determinants of health and mental health do not have consensus definitions, they propose a framework based on two overarching concepts. First, they use the World Health Organization’s definition of social determinants of health as “the conditions in which people are born, grow, work, live, and age” and the “wider set of forces and systems shaping the conditions of daily life.”10 Second, they draw upon the work of Kirkbride and colleagues11 who support universal prevention strategies to address social determinants of health at key points in the human developmental lifespan, such as the antenatal period for mothers at risk for anxiety and depressive disorders. They identify a lack of stable housing, food insecurity, difficulties with health care access, poverty, and a lack of neighborhood recreational space as social determinant mechanisms of mental disorders. Three contributions highlight mechanisms for mental disorders in specific populations. Deidre Anglin and Alexandra Selloni12 review the convergence of structural, social, and biological factors that predispose minoritized individuals to developing psychotic disorders. They assess evidence from three models that rest upon these factors. First, the stimulation, discrepancy, and deprivation model of psychosis posits that stimulation (urban environments, population density, crime exposure), discrepancy (a lack of belonging and social exclusion), and deprivation (inequities in socioeconomic, educational, or material resources) affect cognitive development, dysfunctions in dopamine and glutamate transmission, and chronic inflammation.13 Second, the structural racism model outlines how higher levels of stress from everyday discrimination and social disadvantage—specifically police violence—predispose individuals to psychosis.14 Black and Latinx pregnant mothers who face regular discrimination are at increased risk of developing maternal inflammation and infection compared to White mothers, complications that can predispose their children to psychosis.14 Finally, the neighborhood ethnic density model has revealed that exposure to low levels of ethnoracial minority density in childhood has been associated with reduced cortical thickness in the right fusiform gyrus and right insula.15 Anglin and Selloni assert that enhancing health equity may foster social support, environmental enrichment, neighborhood cohesion, and safety to decrease activation of neural circuitry threat and chronic stress exposures. Adolfo Cuevas and Steven Cole16 dive into one such mechanism across levels—the association between biological inflammation and social discrimination. They define discrimination as “exposure to inequitable treatment,” which they categorize as acute major lifetime events and everyday indignities across social contexts. Their review isolates recurrent biological findings: activation of the amygdala, which perceives environmental threats and regulates emotions, norepinephrine release of the sympathetic nervous system to stimulate inflammatory reactions, and a rise in cortisol from the hypothalamic-pituitary-adrenal axis, which binds to glucocorticoid receptors on immune cells. Basic scientific research has identified five inflammatory markers—CRP, IL-6, fibrinogen, E-selectin, and ICAM-1—that are elevated in racially minoritized groups with higher lifetime exposures to discrimination.17 Cuevas and Cole caution that current studies have limited generalizability across patient populations because they are mostly cross-sectional rather than longitudinal, enroll middle-aged and older adults rather than youth, treat discrimination in isolation from other social determinants, and lack differentiation between major lifetime and everyday forms of discrimination. Nonetheless, their article convincingly makes the case for developing intrapersonal, interpersonal, and structural interventions to reduce discrimination and, consequently, inflammation that may lead to a range of mental disorders. Last, Cristiane Duarte and colleagues18 undertake a systematic review of antiracism interventions for pregnant Black women. They include studies with original data on interventions in obstetric care settings that targeted individual and structural racism. As part of the inclusion criteria, they searched for interventions that incorporated cultural respect and appreciation. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, they searched PubMed for studies that enrolled Black birthing individuals during the pregnancy or delivery period that reported outcome measures from the birthing individuals and their offspring. Out of 1,221 studies, they included five. Interventions occurred in hospitals, prenatal clinics, birthing centers, and in-home visits, representing a variety of service locations. Duarte and colleagues helpfully postulate mechanisms for these interventions: a community doula home visit program may increase breastfeeding rates by building trusting relationships, case management programs may help participants manage pregnancies that improve infant birth weight, culturally tailored cognitive behavioral therapy can reduce depression symptoms in birthing parents, and midwives can affirm respect for, and autonomy of, birthing patients. They conclude that increasing social aids via supportive relationships and the integration of cultural values and orientations in care improves parental and infant outcomes. Taken together, these articles represent a trailblazing effort to advance mechanisms across human domains that have persistently been separated. They raise urgent issues for all of us who are committed to redressing inequities for historically disadvantaged social groups. First, we need clarity about interventions that can be deployed at different levels—by mental health providers, their associated institutions, and the government policymakers and politicians who provide funding for such institutions.19 For instance, supportive social relationships could take the form of innovations introduced by mental health providers and their institutions. Government stakeholders, however, are best equipped to formulate policies to address crime, neighborhood ethnic density and recreational spaces, stable housing, food insecurity, difficulties accessing health care, and poverty. Second, we need to acknowledge that research and policies that isolate mechanisms of mental disorders across these levels can constructively disrupt paradigms of experimental science. For instance, the National Institute of Mental Health stage model of intervention development proceeds along this pathway: Stage 0: basic research → Stage 1: intervention development/refinement → Stage 2: efficacy trials in research clinics → Stage 3: efficacy trials in community clinics → Stage 4: effectiveness trials → Stage 5: implementation and dissemination.20 This model, however, assumes that biological or psychological factors are the primary mechanisms of mental illness for exploration in Stages 0 and 1. Sociocultural factors start at Stage 4 rather than in the basic research stage.21 Those of us committed to reducing health inequities believe that cultural, social, and structural factors need to be addressed now. We need to reimagine experimental paradigms, even if this means recognizing that clinical trials are not always the gold standard of study design. Finally, the papers in this special issue should be the start, not the end, of a conversation about variables that interact across social-structural, cultural, psychological, and biological levels to create and sustain inequities. The 2025 APPA annual meeting will feature researchers and policymakers who specialize in inequity-reduction interventions. We invite readers to join these conversations.