Expanding stress theory: prolonged activation and perseverative cognition

Several theories of the stress-disease link have now incorporated prolonged activation. This article argues that these theories still lack an important element, that is, the cognitive nature of the mechanism that causes stress responses to be sustained. The perception of stress and the initial response to it do not automatically lead to prolonged activation. The active cognitive representations of stressors need to be prolonged in order to extend their physiological concomitants. We call this mediating process perseverative cognition, and it is manifested in phenomena such as worry, rumination, and anticipatory stress. We summarize evidence suggesting that these phenomena are indeed associated with physiological activation, including cardiovascular, endocrinological and immunological parameters. This evidence is still far from sufficient, due to the many methodological insufficiencies in the studies involved. Nevertheless, it makes clear that cognitive phenomena characterized by perseverative cognition may be likely candidates to mediate the effects of stress sources on somatic disease.

We also argue that there is a dearth of evidence supporting the role of prolonged activation. There are a limited number of studies demonstrating prolonged activity related to stressors and emotional episodes, and their methodologies often do not allow unambiguous conclusions. Even more important, the crucial assumption that prolonged activation actually leads to pathogenic states and disease has received hardly any attention yet and therefore is still largely unsupported. There are only a few studies that showed that anticipatory responses and slow recovery from stress predicted disease states.     

Prolonged stress-related cardiovascular activation: Is there any?

Background: Prolonged physiological activation before or after stressors has gained recognition as a decisive element in theories that explain the link between stress and disease, specifically cardiovascular (CV) disease. This view is opposed to the conventional reactivity hypothesis that emphasizes responses during stressors.Purpose: Prolonged activity has not often been an explicit research goal of real-life stress studies. Nevertheless, a growing number of these studies have provided evidence for prolonged activity, often as a secondary research goal.Methods: An overview of this evidence is lacking and is provided in this article.Results: The combined data from the reviewed studies suggest that discrete and chronic stress sources, as well as negative emotional episodes and dispositions, are related to prolonged CV activity of various durations, including sleep periods. On the other hand, evidence supporting the assumption that prolonged stress-related activation predicts disease is still very modest.Conclusions: In this article we suggest that future research of prolonged activation should give priority to (a) the establishment of clear beginnings and endings of stressful events, (b) the prediction of disease by prolonged activation, and (c) potential psychological mediators of stress-related prolonged activation. These mediators may include, for example, worry and rumination, or other processes characterized by perseverative cognition, including unconscious processes. This study was financially supported by a grant of the Netherlands Organization for Scientific Research (NWO).     

Conscious and unconscious perseverative cognition: Is a large part of prolonged physiological activity due to unconscious stress?

Prolonged physiological activity is believed to be a key factor mediating between stress and later disease outcomes. Few studies, however, have investigated the crucial psychological factors that cause prolonged activity. This article proposes that conscious as well as unconscious perseverative cognition are the critical factors. Perseverative cognition indicates repetitive or sustained activation of cognitive representations of past stressful events or feared events in the future. In daily life, most prolonged physiological activity is not due to stressful events but to perseverative cognition about them. We and others have already found evidence that conscious perseverative cognition, i.e., worry, has physiological effects, in both laboratory and real life settings, and that perseverative cognition mediates prolonged responses to stressful events. Yet, there are convincing reasons to expect that unconscious perseverative cognition has an even larger role in stress-related prolonged activity. Firstly, since the greater part of cognitive processing operates without awareness, a considerable part of perseverative cognition is likely to be unconscious too. People may not be aware of most of their stress-related cognitive processes. Secondly, our recent studies have shown that increased activity of the autonomic nervous system continues after conscious perseverative cognition has stopped: It goes on for several hours and even during sleep. This and several other findings suggest that a considerable part of increased physiological activity may be due to unconscious perseverative cognition. The article closes with suggesting methods to test unconscious perseverative cognition and ways to change it, and concludes with stating that the notion of unconscious perseverative cognition potentially opens an entirely new area within stress research.     

Markers of chronic stress: Prolonged physiological activation and (un)conscious perseverative cognition

In daily life, not stressful events themselves but their sustained cognitive representation is likely to cause prolonged physiological activity, which is believed to lead to a pathogenic state and finally somatic disease. The typically human ability to make cognitive representations of past stressful events (rumination) or feared events in the future (worry) is called perseverative cognition (PC). PC is associated with increased activity in various bodily systems, and there is emerging evidence that it mediates the prolonged effects of stressors on physiology and on disease. Yet, there are strong reasons to believe that people may not be aware of the greater part of their stress-related cognitive processes, while several studies suggest that these processes may still cause increased physiological activity, during sleep as well as during waking. This may imply that unconscious PC is an even more important source of prolonged stress-related activity than conscious PC. Thus, ‘unconscious stress’ research has the potential to become a new important area and may yield new important markers of chronic stress.     

Markers of chronic stress: Prolonged physiological activation and (un)conscious perseverative cognition

In daily life, not stressful events themselves but their sustained cognitive representation is likely to cause prolonged physiological activity, which is believed to lead to a pathogenic state and finally somatic disease. The typically human ability to make cognitive representations of past stressful events (rumination) or feared events in the future (worry) is called perseverative cognition (PC). PC is associated with increased activity in various bodily systems, and there is emerging evidence that it mediates the prolonged effects of stressors on physiology and on disease. Yet, there are strong reasons to believe that people may not be aware of the greater part of their stress-related cognitive processes, while several studies suggest that these processes may still cause increased physiological activity, during sleep as well as during waking. This may imply that unconscious PC is an even more important source of prolonged stress-related activity than conscious PC. Thus, ‘unconscious stress’ research has the potential to become a new important area and may yield new important markers of chronic stress.     

Trait and state perseverative cognition and the cortisol awakening response

Perseverative cognition (i.e., rumination, worry) may amplify or maintain cortisol stress responses. The present study examined the effects of trait and state perseverative cognition (PC) on the cortisol awakening response (CAR). We hypothesized that trait PC and state (prior day's) PC would be associated with greater CARs. Undergraduates scoring high (N=77) and low (N=42) on trait PC were included. Participants reported worries about upcoming events and ruminations on past events that occurred throughout the day as a measure of state PC. The next morning, saliva samples were collected 0, 30, 45, and 60min after awakening to assess the CAR. Area under the curve (AUC) and 30-min increase (30-min Inc) were calculated to capture the salivary cortisol total output and increase relative to baseline in the hour after awakening. There was no effect of trait PC on the CAR. In contrast, reports of worrying and/or ruminating the night before predicted greater increases in cortisol concentration and total cortisol output compared to those who neither ruminated nor worried the night before. These effects were not accounted for by depressed mood, anxiety, sleep, or recent stressors. Findings suggest differential effects of trait and state PC on the CAR and highlight the importance of using proximal measures in examining individual differences in the CAR.     

Trait reflection predicts interleukin-6 response to a social-evaluative stressor

Past work has linked negative repetitive thought (worry, rumination) about stressors to sustained stress responses. Less is known about the effects of neutral types of repetitive thought (e.g., reflection) on physiological stress responses. The present study examined whether greater trait reflection was associated with a lower inflammatory response to an acute psychosocial stressor. Thirty-four healthy undergraduate women completed a speech stressor, and plasma interleukin-6 (IL-6), C-reactive protein, and tumor necrosis factor-α levels were assessed before and after the stressor. Higher levels of reflection predicted lower IL-6 responses 1 h after the stressor. Stressor appraisal was not a significant mediator. These preliminary findings stand in contrast to existing evidence that other forms of repetitive thought like worry and rumination may exacerbate or prolong the inflammatory stress response and indicate that reflection is a notable factor worth considering when examining the relationship between stress, inflammation, and health.     

Are All Anxieties Created Equal? Stress-related Networks and Anxiety Phenotypes in Old Age

ObjectiveThe dysregulation of stress-related networks due to chronic symptoms such as severe worry and/or rumination is one of the putative pathways linking anxiety in late-life with cognitive decline and increased cardiovascular burden. Symptoms such as severe worry or rumination respond poorly to standard treatment and drive the morbidity associated with anxiety in older adults. We assessed if any of the neural networks anchored in the stress-related regions of interest (ROIs) are associated with distinct anxiety phenotypes (worry, rumination and global anxiety).MethodsWe recruited older participants (over 50 years of age) with varying levels of worry (N = 91) to undergo resting state fMRI. We computed seed-based connectivity for each ROI: the bed nucleus of the stria terminalis, the paraventricular nucleus of the hypothalamus, habenula, and amygdala. We limited our connectivity analyses to extracted regions for each seeded ROI-based network based on their canonical networks in 1,000 participants (Neurosynth). Using connectivity and clinical factors, we fit cross-validated elastic net models to predict scores on Penn State Worry Questionnaire, Rumination Subscale Questionnaire, Hamilton Anxiety Rating Scale, and Perceived Stress Scale.ResultsWe identified several distinct connectivity patterns that predict anxiety phenotypes’ severity. Greater worry was associated with greater paraventricular nucleus of the hypothalamus -subgenual anterior cingulate cortex, parahippocampal, and olfactory and amygdala-PHC connectivity. Greater global anxiety was associated with lower amygdala-superior temporal gyrus connectivity. Greater perceived stress was associated with lower amygdala-inferior temporal gyrus and amygdala-fusiform gyrus connectivity.ConclusionOur study suggests that various late-life anxiety phenotypes (worry, global anxiety, rumination) may be associated with varying functional connectivity related to stress and emotion regulation. This may aid in the development of future targeted interventions.     

Intolerance of uncertainty,worry, and rumination in major depressive disorder and generalized anxiety disorder

Intolerance of uncertainty (IU) can be defined as a cognitive bias that affects how a person perceives, interprets, and responds to uncertain situations. Although IU has been reported mainly in literature relating to worry and anxiety symptoms, it may be also important to investigate the relationship between IU, rumination, and depression in a clinical sample. Furthermore, individuals who are intolerant of uncertainty easily experience stress and could cope with stressful situations using repetitive thought such as worry and rumination. Thus, we investigated whether different forms of repetitive thought differentially mediate the relationship between IU and psychological symptoms. Participants included 27 patients with MDD, 28 patients with GAD, and 16 patients with comorbid GAD/MDD. Even though worry, rumination, IU, anxiety, and depressive symptoms correlated substantially with each other, worry partially mediated the relationship between IU and anxiety whereas rumination completely mediated the relationship between IU and depressive symptoms.     

Distinguishing worry from rumination in older people: a preliminary investigation

Anxiety and depression are common mental health problems in later life. Since worry and rumination are thought to underpin the respective primary cognitive processes in anxiety and depression, we developed a measure to distinguish worry from rumination in later life. The Ruminative Response Scale was adapted to include items that characterise the cognitive features of worry. We examined its properties using 92 clinical and non-clinical participants, aged over 65. Factor analysis demonstrated a three-factor structure: brooding, reflection and worry with internal consistencies of alpha = 0.72, alpha = 0.67 and alpha = 0.55 respectively. We found no evidence for concurrent validity of these factors using the Penn State Worry Questionnaire. Modest but significant associations between reflection and brooding (r = 0.36) and reflection and worry (r = 0.2) were found. Brooding and worry sub-scales remained unrelated. We suggest that it is possible to distinguish worry from rumination in older people and that differentiating between their key underlying characteristics in the assessment of mood problems may enhance the targeting and evaluation of cognitive-behavioural therapy for anxiety and depression in later life. Future research with a substantial clinical sample is needed to explore the underlying dimensions and correlates of worry in later life.