HPA-axis stress reactivity in clinically depressed youth: New evidence of impaired feedback inhabition?
ABSTRACT: Given the established link between youth depression and stress, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the Hypothalamic-Pituitary-Adrenal Axis. Early studies using direct biological probes suggested a potential deficit in the HPA-axis’ inhibitory feedback mechanism, but the relevance of these findings to psychosocial stress regulation is unclear. Studies using field “biomarkers” (e.g., cortisol awakening response) also suggest atypical HPA-axis functioning, but whether this effect is due to deficits in inhibitory feedback mechanisms is unknown because we know little about what these field biomarkers actually mark in terms of fundamental HPA-axis biology. Finally, studies using laboratory-based psychosocial stress paradigms have produced highly conflicting findings likely due to methodological limitations that have precluded the proper examination of HPA-axis regulatory processes (e.g., inhibitory feedback). Therefore, this talk will present a new analytic approach to cortisol stress reactivity that allows for the simultaneous modeling of separate components of the HPA-axis response (e.g., intensity of activation, inhibitory threshold, regulatory capacity). We used this approach to examine the cortisol response of 35 clinically depressed youth (Age 9-16; 18 girls, 17 boys) and 70 age- and sex-matched non-affected peers who underwent a well validated laboratory stress task (socially evaluative cold press). Results suggest that depressed youth have higher peak responses than their peers due to a more prolonged (later peak latency), but not more intense, activation phase. This finding suggest group differences in either 1) inhibitory threshold (i.e., level of cortisol exposure required to activate the axis’ feedback inhibition system) or 2) inhibitory shift (i.e., point at which the ratio of inhibitory and excitatory input into the axis shifts to greater excitatory to greater inhibitory input). Functional implications of these findings to the phenomenology of depression will be considered.