Effects of perceived control and cognitive coping on endocrine stress responses to pharmacological activation

Abstract

Background: The hypothalamic-pituitary-adrenal (HPA) axis may mediate negative health effects of stress. It is sensitive to cognitive/emotional factors like novelty, perceived control, and coping. Psychological intervention that reduces novelty and enhances cognitive coping and sense of control can reduce cortisol responses to pentagastrin, a pharmacological HPA activator. This study attempted to identify the core factors that modulate HPA axis activity in this model.

Methods: Varying instructions were administered prior to drug exposure in a two-visit (placebo first) pentagastrin infusion paradigm. Healthy subjects (n = 40) were randomly assigned to one of four instruction groups: 1) standard instruction (SI); 2) full cognitive intervention (CI); 3) the CI control component alone; or 4) the CI novelty reduction/coping components alone. Blood samples were obtained via intravenous catheter before and after pentagastrin.

Results: Subjects receiving an intervention had smaller cortisol responses than subjects receiving standard instructions. Coping alone had as strong an impact as the more complex intervention that combined coping and control. Control alone also reduced cortisol but its HPA impact appeared less robust.

Conclusions: Brief psychological manipulation can significantly reduce HPA activation in challenge paradigms. Cognitive preparation that focused on side effects, reduced potential surprise, and enhanced cognitive coping modulated HPA axis activity as effectively as a previously tested intervention that combined coping and control manipulations. A sense of control alone also reduced cortisol release. The results support development of control or coping techniques to combat negative health effects of stress that are mediated by HPA axis activation.

Figure 1

Cortisol responses to pentagastrin in healthy subjects randomly assigned to standard instructions or one of three intervention groups. Left panel contains raw data (mean ± SE). Right panel shows response scores (AUC response ± SE). Asterisks indicate a significant difference (p < .05) from the standard instruction group.

Figure 2

Corticotropin (ACTH) responses to pentagastrin in healthy subjects randomly assigned to standard instructions or one of three intervention groups (mean ± SE).

Figure 3

Symptom (left) and anxiety (right) responses to pentagastrin (means ± SE) in healthy subjects randomly assigned to standard instructions or one of three intervention groups.

Figure 4

Path analysis model linking cognitive variables, bodily sensations, and cortisol responses to pentagastrin, with good fit (χ² (9, N = 39) = 9.23, p = .42, CFI = .99, RMSEA = .03, SRMR = .07), showing standardized partial regression coefficients. Rectangles indicate observed variables, circles indicate latent variables (d = disturbance or residual terms), curved line with double-headed arrow indicates covariance, and straight arrows indicate regressions. CFI = comparative fit index, RMSEA = root mean square error of approximation, SRMR = standardized root mean square residual, Δ = change from baseline to 5 minutes post-pentagrastrin. Good fit = chi square p > .05, CFI > .90, RMSEA < .06, SRMR < .10.