Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the HPA or stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5–18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA.

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

“…This CRP profile may underlie the increased vulnerability to anxiety- and depressive-like behaviors observed in these animals (Brocardo et al, 2012; Hellemans et al, 2008; 2010a,b; Raineki et al, 2016), consistent with the clinical literature indicating that individuals exposed to alcohol during gestation show increased vulnerability to mental health problems when compared to controls (Famy et al, 1998; O’Connor and Kasari, 2000; Pei et al, 2011). Moreover, it has been proposed that exposure to adversity and/or stress has a greater impact on individuals with PAE than on unexposed individuals, resulting in an even higher rate of mental health problems in that population (Hellemans et al, 2010a; McLachlan et al, 2016; Raineki et al, 2014). Indeed, we have previously demonstrated that PAE rats exposed to chronic, unpredictable but mild stressful experiences in adulthood show increased anxiety- and depressive-like behaviors (Hellemans et al, 2008, 2010a,b).…”

Economic, social, and physiological resilience predict brain structure and cognitive performance in 9 - 10-year-old children

“…Further, adverse perinatal factors, such as low birth weight 16 and maternal substance use 17 , have also been associated with stress dysregulation in childhood and adolescence. These same adverse perinatal factors are associated with cortical alterations 18,19 .…”

Circadian cortisol dynamics across reproductive stages and in relation to breastfeeding in the Philippines

“…In the nonpregnant state, salivary cortisol follows a marked diurnal rhythm, with levels high in the morning, peaking approximately 30 minutes after waking (termed the cortisol awakening response [CAR]), and then reaching a nadir prior to bed. When cortisol does not follow a normal pattern of decline across the day, as indicated by elevated evening cortisol and a shallower diurnal slope, this has been associated with chronic stress and the development of adverse mental and physical health outcomes (Cohen et al, ; Desantis, Kuzawa, & Adam, ; McLachlan et al, ; Obel et al, ; Thayer & Kuzawa, ; Thayer, Feranil, & Kuzawa, ). Despite the well‐known diurnal changes in salivary cortisol levels throughout the day, little is known about how different aspects of the diurnal cortisol curve vary across pregnancy.…”