Refining the multisystem view of the stress response: Coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict

Highlights

• We investigated coordination of HPA and ANS responses to an interpersonal stressor.

• Responses were aligned across systems over time (matched phase coordination).

• Women's levels of HPA and ANS activation were related (average level coordination).

• Positive pre-task anticipation predicted stronger HPA–ANS coordination for women.

• Post-task stress appraisals related to HPA, but not ANS, response trajectories.

Abstract

This study investigated associations among young adults' hypothalamic–pituitary–adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period (“matched phase coordination”), and association between overall levels of cortisol and sAA in response to conflict (“average level coordination”). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol–sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed.

Introduction

Multiple psychophysiological systems are involved in perceiving, reacting to, and recovering from threat and challenge [56]. Specialized responses from different systems enable more finely calibrated management of stress than reliance on a single system but depend on well-tuned coordination between systems, as well as between psychological and physiological states. Stress research has typically focused on the activation of individual subsystems – in particular, either the hypothalamic–pituitary adrenal (HPA) axis or the sympathetic branch of the autonomic nervous system (ANS) – during a standardized physical or psychological challenge task. This leaves an incomplete picture of how multiple stress response systems work together within individuals, particularly in the context of naturalistic interpersonal stressors encountered in daily life [20], [41]. During adolescence and early adulthood, sensitivity to interpersonal stressors, particularly among females, increases [52], [53]. Given that miscalibrated responses to interpersonal threat are thought to underlie mental health risk emerging during this period (e.g., [12], [27], [42], [43]), it is important to understand how young adults typically respond to such stressors, and how these responses do or do not map onto subjective stress.

The present study was designed to further a multisystem view of the stress response and its implications for well-being by answering the following questions in a community sample of dating couples: (1) Are young adults' cortisol (HPA marker) and salivary alpha-amylase (sAA; ANS marker) trajectories in response to interpersonal stress coordinated across systems? In what way/s does this coordination occur? and (2) How does subjective stress going into and following the stressor relate to cortisol and sAA response trajectories, as well as the degree of within-person cortisol–sAA coordination? Answering these questions promises to both advance basic research on the nature of the stress response and inform stress interventions aimed at young individuals or couples.

The two main components of the physiological stress response are the HPA axis and the sympathetic branch of the ANS [7]. The ANS is designed to produce a rapid response, preparing the body to actively cope with a stressor through effects on the cardiovascular and respiratory systems and the release of stored catecholamines. The HPA system activates a slower cascade of secretory signals that culminate in the release of cortisol from the adrenal gland, adapting the body to stress conditions by inhibiting non-emergency vegetative processes such as sleep, sexual activity, and growth [56]. While both respond to psychosocial stress, the meaning of response within each system may differ; ANS activity is thought to be less valenced and reflective of both approach- and withdrawal-related arousal, whereas HPA activity is more specifically associated with negative affect and withdrawal (e.g., [6], [39]). In line with this view, ANS measures have been associated with an “effort” or “challenge” component of stress, and HPA measures with a “distress” component [33].

Salivary cortisol offers a noninvasive measure of HPA activity [21], and sAA, an enzyme produced in response to activation of ANS innervation of the salivary glands, is used as a surrogate marker of autonomic activity [19], [36]. The HPA and ANS are interrelated at the neural level, allowing each system to potentially influence the response of the other [48], [55], [58], [59]. Functional relations between the two systems remain under debate, with arguments existing for permissive, suppressive, stimulating, as well as preparative effects [35], [48].

There have been numerous calls for studies to empirically examine coordination of these systems within the same individuals, particularly when responding to psychological stressors encountered in daily life [3], [18], [55], [60], [61], [62]. Salivary measures of both HPA and ANS activity promise a minimally invasive method of stress system assessment that is unlikely to generate additional stress. However, information on the nature of response across systems remains sparse and is often limited by restricted measurement and analysis of response trajectories.

Very few studies have examined coordination between HPA and ANS responses, and the means of operationalizing such coordination have remained fairly simplistic — typically, correlations between post-stress cortisol and sAA levels or pre-post stress difference scores. We propose two possible forms of coordination (see Fig. 1 for illustrations). “Average level coordination” (Figs. 1A and C) occurs when the overall strength of HPA activation, reflected by an individual's mean cortisol across stress phases (including pre-stress anticipation, stress-related reactivity, and recovery), predicts the level of his/her sAA response trajectory. This could attest to a balance of threat and challenge reactions to stress, based on parallel calibration of the systems as a whole and/or uniform sensitivity to a particular type of stressor. Interestingly, previous research has generally shown nonsignificant correlations between cortisol and sAA in adults [37], [53], [55], [63] and in children [18], although a few studies have found significant correlations when sub-groups based on sex [26] or maltreatment status [17] were analyzed. Single time-point correlations, as opposed to measures of association involving the entire response trajectory, may also have contributed to null findings.

“Matched phase coordination” occurs when changes in HPA activation across different phases of the stress response are aligned with changes in ANS activation (Figs. 1B and C). In other words, a person's relative increases in cortisol from one time point to the next predict increases in sAA, and response trajectories unfold in a parallel fashion (see [30], for further explanation of cross-system coordination). This may offer a more situational measure of how threat reactions (indexed by HPA activity) trigger effort/challenge reactions (indexed by ANS activity) to confront the stressor within a given stress episode. It should be noted that whereas peak ANS response is reflected in sAA within a few minutes, there is an approximately fifteen to twenty minute lag between peak cortisol release in the blood and salivary measures [49]. This means that cortisol–sAA associations in saliva samples likely represent a lagged effect of earlier HPA on later ANS response. A study testing both forward- and backward-lagged effects in an all-male sample yielded mixed evidence for positive vs. negative associations between cortisol and sAA [10]. The only previous study of matched phase coordination as operationalized here found positive cortisol–sAA associations only among non-depressed women and their infants [30]. Given this and other evidences that discordance between HPA and ANS responses may signal mental health problems [2], a key task at this point is to determine how these systems are functionally related in real-life stress contexts and what predicts coordination vs. discordance.

One potentially important predictor is subjective stress preceding and following the stressor. Stress appraisals have been shown to mediate effects of self-perceived stress reactivity on actual physiological response, and their modification may help to explain impacts of cognitive behavioral stress management on cortisol reactivity [15], [50]. Recent conceptualizations of stress adaptation point to a constellation of response across physiology and behavior that may offer greater insight into adjustment than measuring either domain on its own [54]. To fully appreciate the conditions for response within and across systems, and ultimately to make recommendations for stress regulation, the links between anticipatory/perceived stress and physiological responses must be clarified.

Past research offers evidence for variable coupling between subjective stress and stress physiology. For example, a number of studies have related anticipatory appraisals of high threat and/or low coping ability to higher cortisol responses to psychosocial stress [16], [23], [57], though studies in adolescents have either shown no effect of pre-stress ratings [40] or related low coping appraisals to lower cortisol responses [51]. Research has also linked anticipatory stress appraisals to markers of ANS response (i.e., blood pressure; [23]), yet other researchers showed no effect on ANS markers (i.e., norepinephrine and epinephrine; [57]). Similarly, appraisals during and following stress have shown inconsistent associations with physiology. Several studies have linked perceived stress to HPA and/or ANS responses [1], [40], [46], but others found no effect of post-stress appraisals or pre-post change in stress ratings [11], [16]. Although most of these studies investigated effects on stress reactivity, some showed effects on post-stress recovery [23], [50].

Some of these differences may have to do with variable response measurement — i.e., post-stress HPA/ANS activity levels vs. change from pre-post stress vs. change from post-stress to recovery. Few researchers have addressed the entire response trajectory, though a more comprehensive investigation of subjective stress and cortisol across multiple time points revealed significant correlations between the two either contemporaneously (in a pharmacological challenge paradigm) or after a five-minute lag (in a psychosocial stress task) [49]. There are also indications that the type of stressor makes a difference, with more interpersonally threatening tasks – i.e., public speaking – eliciting stronger psychological–physiological response associations [1].

Together, these studies show that the quality of stress anticipation and perceptions may be decisive for HPA and ANS responses, but a clearer understanding of which cognitive processes predict which aspects of response requires a multisystem investigation of physiological stress trajectories. It is important to determine which cognitions underlie HPA and ANS response components, given that the degree of reactivity and/or recovery in each relates uniquely to mental health. In particular, blunted sAA responses and high cortisol levels/incomplete recovery following stress have been associated with depression and related risk factors [5], [34], [46]. As suggested by Burke et al.'s [5] review, the ability to recover efficiently after a stressor has terminated may be even more important than cortisol levels themselves in determining well-being. Much of this work has been based on responses to standard pharmacological challenge or performance tasks (i.e., the Trier Social Stress test), which reliably elicit stress responses but may not offer a complete picture of the processes actually contributing to mental health.

In childhood and adolescence, the ANS and HPA systems respond differently to interpersonal vs. performance tasks [53], and certain aspects of psychosocial adjustment (i.e., attachment styles) have been associated with HPA responses to interpersonal conflict but not to performance stress [9], [29]. Moreover, developmental increases in the sensitivity of stress responses are stronger for interpersonal than for performance tasks [53]. This increased sensitivity to interpersonal stress parallels increases in developmental risks for depression, anxiety, and other disorders associated with stress dysregulation.

To begin to understand the basis for such disorders, it is important to examine young adults' regulation of stress systems as they respond to the interpersonal conflicts that naturally arise within close relationships. We are aware of no published studies that assess both cortisol and sAA responses to interpersonal stress within a close adult relationship, and of only three studies of parent–child relationships [18], [30], [31]. Thus, research on normative adolescent/young adult couples' HPA and ANS responses to interpersonal relationship stress is urgently needed to recognize the basis for emergent mental health vulnerabilities and inform intervention targets.

In this study, we set out to advance a multisystem conceptualization of the stress response by investigating links among cortisol and sAA trajectories and subjective stress in the context of a common interpersonal stressor. To this end, a community sample of young adult dating couples was recruited for a laboratory interaction study involving the discussion and attempted resolution of a relationship conflict (see [24], [25] for further background on and validation of the stress task). Saliva samples collected before and after the conflict were used to measure HPA (via cortisol) and ANS (via sAA) responses from pre-task anticipation through post-task recovery phases. To address the primary study questions posed above, we used multilevel growth curve modeling to test average level and matched phase coordination across cortisol and sAA response trajectories, as well as effects of pre- and post-task subjective stress ratings on cortisol and sAA trajectories and coordination between the two. On the basis of prior research, we hypothesized that stress responses would be coordinated across systems within individuals, particularly for those who gave more positive/less negative ratings before and after the conflict. We further hypothesized that negative anticipation of the conflict and perceived stressfulness and negativity post-conflict would predict heightened cortisol levels following stress but less dynamic reactivity/recovery, and lower sAA levels.