Association of childhood adversity with HPA axis activity in children and adolescents: A systematic review and meta-analysis

Abstract

Childhood adversity (CA) is associated with alteration of the hypothalamus-pituitary-adrenal (HPA) axis. We conducted a meta-analysis to synthesize existing evidence on the association between CA and HPA axis activity among children and adolescents and investigate four research questions: (1) Is CA associated with different aspects of the HPA axis (i.e., diurnal cortisol, acute stress response, chronic cortisol levels)?, (2) Does this association vary by the child’s age?, (3) Are threat and deprivation dimensions of CA differentially associated with HPA axis activity?, and (4) Does this association depend on both the dimension and timing of CA? Meta-analyses were conducted with 129 studies reporting 506 effect sizes. Results showed significant associations between CA with higher afternoon cortisol levels (r = 0.053), a flatter diurnal slope (r = 0.048), more blunted reactivity (r = –0.043), and higher hair cortisol concentration (r = 0.098), but not other cortisol indicators (morning cortisol, cortisol awakening response, daily output, and cortisol recovery). Older children and adolescents had more pronounced blunted reactivity and steeper recovery with CA than younger children. Threat and deprivation did not differ in overall impact for any cortisol indicator; however, there are timing-dependent associations specific to threat or deprivation for some cortisol indicators. For instance, threat was associated with heightened reactivity when occurred before middle childhood, and with blunted reactivity when occurred after age 15 years; in contrast, deprivation was associated with blunted reactivity regardless of its timing. Findings could inform targeted interventions to reduce negative impacts of CA on development.