Longitudinal analysis of the brain and hypothalamic-pituitary-adrenal axis stress systems and risk for non-suicidal self-injury

Abstract

Background: Non-suicidal self-injury (NSSI) is the harming of oneself without the intent to die and is reported by about 18% of adolescents. The brain and hypothalamic-pituitary-adrenal (HPA) axis stress systems undergo widespread changes during adolescence. There is evidence that alterations in these systems are related to NSSI engagement. Indeed, prior literature has identified some reliable alterations in frontal regulatory control of the amygdala as well as in HPA axis reactivity in adolescents who engage in NSSI compared to those who do not. This work has predominantly used variable-centered analyses. Emerging work using variable-centered and person-centered analyses has identified some meaningful heterogeneity among adolescents who do engage in NSSI. Despite these advances, there is little work characterizing how these biological processes unfold across development for those who engage in NSSI. The following multi-level, longitudinal studies aim to identify patterns in the development of the brain and HPA axis using variable-centered analyses in conjunction with person-centered analyses. Study 1 Methods: This study employs a large, community-representative sample of adolescents to examine neurodevelopmental patterns in the amygdala and superior frontal reactivity to emotional stimuli and fronto-limbic resting state functional connectivity. Study 1 Results: Person-centered analyses identified 5 neurodevelopmental trajectories. Participants in a person-centered derived group with a normative developmental profile first reported engaging in NSSI later than a profile typified by dynamic change across study time points. Variable-centered analyses found that decreased frontal reactivity to emotional stimuli at baseline and decreased slope of change of fronto-limbic resting state functional connectivity were associated with increased risk for NSSI. Study 2 Methods: This study includes a sample of adolescents at high risk for NSSI with HPA axis metrics in addition to measures of the brain’s stress system (including the amygdala and medial prefrontal cortex reactivity to emotional stimuli and fronto-limbic resting state functional connectivity). Study 2 Results: Person-centered analyses identified 6 developmental trajectories of the brain and HPA axis. Two person-centered profiles in which participants in part demonstrated a pattern of blunted frontal regulatory control were found to differ in severity of NSSI. Variable-centered analyses found that decreased baseline fronto-limbic resting state functional connectivity was associated with increased risk of NSSI, increased severity of NSSI, and higher number of episodes of NSSI. Decreased baseline HPA axis reactivity was associated with increased risk of NSSI and increased severity of NSSI while a more positive slope of change in HPA axis reactivity was associated with increased severity of NSSI. Discussion: The person-centered analyses provide novel insights into within-group heterogeneity among adolescents who engage in NSSI. The variable-centered analyses replicate and extend past work by providing longitudinal evidence of biological signatures associated with NSSI. These findings provide new insights into developmental alterations in the brain and HPA axis which are related to NSSI which may have implications for intervention efforts with this population.