How children's anxiety symptoms impact the functioning of the hypothalamus–pituitary–adrenal axis over time: A cross-lagged panel approach using hierarchical linear modeling

Abstract

Anxiety symptoms in childhood and adolescence can have a long-term negative impact on mental and physical health. Although studies have shown dysregulation of the hypothalamus-pituitary-adrenal axis is associated with anxiety disorders, it is unclear how and in what direction children's experiences of anxiety symptoms, which include physiological and cognitive-emotional dimensions, impact the functioning of the hypothalamus-pituitary-adrenal axis over time. We hypothesized that higher physiological symptoms would be contemporaneously associated with hypercortisolism, whereas cognitive-emotional symptoms would be more chronic, reflecting traitlike stability, and would predict hypocortisolism over time. One hundred twenty children from the Concordia Longitudinal Risk Research Project were followed in successive data collection waves approximately 3 years apart from childhood through midadolescence. Between ages 10-12 and 13-15, children completed self-report questionnaires of anxiety symptoms and provided salivary cortisol samples at 2-hr intervals over 2 consecutive days. The results from hierarchical linear modeling showed that higher physiological symptoms were concurrently associated with hypercortisolism, involving cortisol levels that remained elevated over the day. In contrast, longitudinal results over the 3 years between data collection waves showed that chronic worry and social concerns predicted hypocortisolism, showing a low and blunted diurnal cortisol profile. These results have implications for broadening our understanding of the links between anxiety, the stress response system, and health across the course of development.

Lower cortisol levels and attenuated cortisol reactivity to daily-life stressors in adults with 22q11.2 deletion syndrome

“…Although cortisol levels are elevated in children with 22q11DS (Jacobson et al, 2016;Sanders et al, 2017), we found lower cortisol levels in adults with 22q11DS, indicating impairments in the developmental trajectory of the endocrine systems. This is in line with recent insights from a longitudinal study in HCs showing that "short term" physiological symptoms in children were associated with hypercortisolism, while chronic worry and social concerns predicted lower cortisol levels 3 years later (Ma et al, 2018). A similar developmental trajectory, involving over-activation, over-sensitization, or some sort of exhaustion of the endocrine or signaling systems over the years, was previously suggested for DA in 22q11DS (Boot et al, 2008a,b).…”

Adolescent anxiety disorders and the developing brain: comparing neuroimaging findings in adolescents and adults

“…31 Factors that affect HPA axis activities include circadian rhythm disturbances, stress and caffeine, particularly during adolescence. 32 The dysregulation of HPA axis activities during adolescence increases the risk of developing anxiety disorders.…”

Social support correlates with glucocorticoid concentrations in wild African elephant orphans

“…Given the challenges experienced by these orphans, including receiving more aggression from other individuals 23 , we surmised they would show the greatest fGCM concentrations among the study subjects because increased secretion of GCs is traditionally equated with greater stress. We speculate our opposite results may be because the stress response is complicated and adrenal glands can exhibit either hyper-or hypo-secretion depending on the type and duration of a stressor 7,[38][39][40] . Longterm social stressors, especially those whose onset is during developmental stages, can cause prolonged hypersecretion of GCs that eventually down-regulate adrenal activity, which could be an adaptive response that prevents harmful effects of consistently elevated GC concentrations 41,42 .…”

“…* denote where the estimated 95% confidence interval did not overlap zero. termed hypocortisolism that has been associated with physiological problems such as autoimmunity, depression, and excessive fatigue in humans (Homo sapiens); skin and oral lesions in black rhinos (Diceros bicornis); and depressive behavior, vertebral problems and hematological anomalies like anemia in horses (Equus caballus) 38,40,[43][44][45][46][47] . Supposing the absence of family initially causes a prolonged rise in GC secretion for non-natal orphans, we are potentially observing the results of an eventual downregulation of the adrenals over time given we sampled several years after the death of orphans' mothers.…”