Altered stress system reactivity after pediatric injury: Relation with post-traumatic stress symptoms

Abstract

Injury is the leading cause of death and disability in childhood. Injured children are at high risk for developing alterations in stress response systems and post-traumatic stress symptoms (PTSS) that may compromise long-term physical and psychological health. In a prospective, observational cohort study, we examined individual differences in, and correlates of, stress-reactivity of the hypothalamic-pituitary-adrenal axis (HPA; salivary cortisol) and autonomic nervous system (ANS; salivary alpha amylase, sAA) following pediatric injury. Participants were 8-15 years of age and hospitalized for traumatic brain injury (TBI; n=55; M age =13.9 yrs; 40 males) or extracranial injury (EI; n=29; M age 12.3 yrs, 20 males) following vehicular accidents. Six months post-injury, saliva was collected before and after the Trier Social Stress Test and later assayed for cortisol and sAA. Relative to a healthy non-injured comparison group (n=33; M age =12.5 yrs, 16 males), injured children (ages 8 to 12 years), but not adolescents (ages 13 to 15 yrs), had higher cortisol levels; regardless of age, injured participants showed dampened cortisol reactivity to social evaluative threat. Compared to participants with EI, children with TBI had elevated cortisol and adolescents had elevated sAA. With respect to PTSS, individual differences in sAA were negatively correlated with avoidance in the TBI group and positively correlated with emotional numbing within the EI group. Importantly, psychological and neurobiological sequelae were weakly related to injury severity. Given the high prevalence of pediatric injury, these sequelae affect many children and represent a significant public health concern. Consequenty, surveillance of post-traumatic sequelae should include the full spectrum of injury severity. Monitoring the activity, reactivity, and regulation of biological systems sensitive to environmental insults may advance our understanding of individual differences in sequelae and adaptation following traumatic pediatric injury.

A Tilted Axis: Maladaptive Inflammation and HPA Axis Dysfunction Contribute to Consequences of TBI

“…Age at the time of injury in adults does not seem to affect vulnerability to HPA axis dysfunction after TBI as most studies report no correlation with age (93). After pediatric TBI, though, children under the age of 12 are more susceptible to HPA dysfunction after injury as compared to older adolescents (106). In fact, one study found all surveyed children with mild to severe TBI have significantly suppressed CORT release in response to HPA activation through insulin tests (107).…”

The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression—The Glucocorticoid Deficit Hypothesis

“…Finally, adversities suffered in adulthood also decrease HPA-axis function on the long run (Carsia and McIlroy, 1998 ; Dayan et al, 2016 ; Pinto et al, 2016 ; Ewing-Cobbs et al, 2017 ). Such stressors include malnutrition, intimate partner violence, traumatic brain injury, and traumatic stress.…”

Evidence Limitations in Determining Sexually Dimorphic Outcomes in Pediatric Post-Traumatic Hypopituitarism and the Path Forward

“…The second pathway by which ACEs could relate to the occurrence of PTHP is when TBI is followed by ACEs. Childhood TBI can also change stress responsiveness by epigenetic mechanisms (127,132). Furthermore, psychiatric co-morbidities and PTSD are both known sequelae of TBI (133,134) and both are associated with alterations in the HPA axis by similar mechanisms (135,136).…”