Socioeconomic Disparities in Hypothalamic-Pituitary-Adrenal Axis Regulation and Prefrontal Cortical Structure

Abstract

Socioeconomic disadvantage during childhood predicts an increased risk for mental health problems across the life span. Socioeconomic disadvantage shapes multiple aspects of children's proximal environments and increases exposure to chronic stressors. Drawing from multiple literatures, we propose that childhood socioeconomic disadvantage may lead to adaptive changes in the regulation of stress response systems including the hypothalamic-pituitary-adrenal (HPA) axis. These changes, in turn, affect the development of prefrontal cortical (PFC) circuitry responsible for top-down control over cognitive and emotional processes. Translational findings indicate that chronic stress reduces dendritic complexity and spine density in the medial PFC and anterior cingulate cortex, in part through altered HPA axis regulation. Socioeconomic disadvantage has frequently been associated with reduced gray matter in the dorsolateral and ventrolateral PFC and anterior cingulate cortex and lower fractional anisotropy in the superior longitudinal fasciculus, cingulum bundle, and uncinate fasciculus during middle childhood and adolescence. Evidence of socioeconomic disparities in hair cortisol concentrations in children has accumulated, although null findings have been reported. Coupled with links between cortisol levels and reduced gray matter in the PFC and anterior cingulate cortex, these results support mechanistic roles for the HPA axis and these PFC circuits. Future longitudinal studies should simultaneously consider multiple dimensions of proximal factors, including cognitive stimulation, while focusing on epigenetic processes and genetic moderators to elucidate how socioeconomic context may influence the HPA axis and PFC circuitry involved in cognitive and emotional control. These findings, which point to modifiable factors, can be harnessed to inform policy and more effective prevention strategies.

Keywords: Early-life stress; Frontolimbic circuitry; Glucocorticoids; Prefrontal cortex; Socioeconomic disadvantage; Structural neuroimaging.

Figure 1

Integrative model highlighting the role of chronic stress and physiological stress mediators in the neurobiological mechanisms underlying socioeconomic disparities in cognitive and emotional control. Socioeconomic disadvantage leads to elevated exposure to chronic stressors, which may influence multiple stress response systems (e.g., autonomic nervous system, hypothalamic-pituitary-adrenal [HPA] axis, immune system) during childhood and adolescence, in turn impacting the development of prefrontal cortical (PFC) and frontolimbic circuitry underlying cognitive and emotional control. Although our review focuses on the HPA axis, multiple physiological systems are likely involved in these mechanisms. Socioeconomic disadvantage has been associated with altered HPA axis function and reduced PFC gray matter during childhood and adolescence. Beyond chronic stress, other proximal pathways, including differences in cognitive stimulation, are involved; these are not pictured here. ACC, anterior cingulate cortex; dlPFC, dorsolateral PFC; vlPFC, ventrolateral PFC.

Figure 2

(A) Stress-induced increases in hypothalamic-pituitary-adrenal axis activation culminate in the release of glucocorticoids, which bind to receptors in multiple regions of the developing brain, including the medial prefrontal cortex (PFC), anterior cingulate cortex (ACC), amygdala, and hippocampus. (B) Similar to findings from nonhuman animal models, associations between altered cortisol levels and PFC and ACC structure have been found in studies of humans. Findings across multiple literatures suggest that frontolimbic circuits may be especially vulnerable. Figure created using BioRender.com. ACTH, adrenocorticotropic hormone; AVP, arginine vasopressin; CRH, corticotropin-releasing hormone.