Handbook of Clinical Gender Medicine. Группа авторов

Chronic Stress and Allostatic Load

      Robert-Paul Juster · Sonia J. Lupien

      Center for Studies on Human Stress, Fernand-Seguin Research Center, Louis-H. Lafontaine Hospital, Montreal, Que., Canada

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      Abstract

      The biopsychosocial signatures for stress-related conditions are age, sex, and gender specific. The trajectories of these diseases are furthermore dynamic as they manifest themselves differently throughout lifespan development and in the context of broader social, cultural, and historical factors. Delineating the effects of chronic stress on the brain and body therefore requires approaches that capture the complexities of the predetermined sex of the individual and the acquired gender throughout the life cycle.Targeting these complex risk factors and promoting protective factors can advance person-centered approaches in medicine. With the goal of refining the diagnosis, treatment, and prevention of diverse diseases, this chapter presents recent progress recorded in the literature on stress-related diseases, highlighting the allostatic load model that represents the biological damage individuals incur when chronically stressed.

      Copyright © 2012 S. Karger AG, Basel

Stress is broadly defined as a real or interpreted threat to an individual’s physiological and psychological integrity that results in biological and behavioral responses [1]. While acute stress is healthy, chronic stress is a major risk factor for many conditions discussed in this textbook. By focusing on nuances stemming from age, sex, and gender, this chapter will introduce the reader to advances in measuring chronic stress using the allostatic load (AL) model [2].

      The Measurement of Stress

The magnitude of stress experienced by an individual can be assessed by measures of environmental stressor frequencies, subjective psychological ratings, and/or objective biological indices related to stress responses. Situations that are novel or unpredictable, threaten self-preservation, and/or diminish one’s sense of control will additively contribute to stress responses [3, 4]. This response refers to the sympathetic-adrenal-medullary axis release of catecholamines within seconds and the hypothalamic-pituitary-adrenal axis secretion of glucocorticoids several minutes thereafter. Resulting stress hormones like adrenalin and cortisol mobilize the energy necessary for fight-or-flight responses first described by Walter Cannon.

According to Sterling and Eyer [5], this metabolic allocation of catabolic energy exemplifies allostasis, defined as the biological processes that facilitate dynamic stabilization to environmental demands. The price the brain and body pay for cumulatively generating allostatic responses is called AL [2], referring to the multisystemic biological damage caused by chronic stress. As this chapter will reveal, AL is easily measurable using indices that currently incorporate various peripheral biomarkers. These are related to older age, distributed differently according to sex, and moderated by gendered risk factors and protective factors discussed in our chapter’s later sections.

      Clinical Aspects

      Neurological Regulation and Allostatic Load

The brain is central to allostasis and AL. Stress hormones bypass the blood-brain barrier to bind to three key receptor-dense regions: the prefrontal cortex, the amygdala, and the hippocampus. Chronic production of cortisol is believed to be neurotoxic, leading to frontal lobe malfunctioning, amygdaloidal hypertrophy, and hippocampal atrophy associated with region-specific cognitive impairments and emotional dysregulations throughout the life cycle [6]. Furthermore, individual differences in constitutional (e.g. genetics, development, and experience), behavioral (e.g. coping and health habits), and historical (e.g. trauma/abuse, major life events, and stressful environments) factors also modulate an individual’s sensitivity to chronic stress that can further damage the brain and body. Of critical importance is the timing and duration at which major stressors and/or traumas are experienced, as this will profoundly affect neurological development that, in turn, can exacerbate the inherent vulnerabilities conferred onto individuals.

      Life Cycle Model of Stress

Lupien et al. [6] recently proposed that the consequences of chronic stress and/or trauma at different life stages depend on which brain regions are developing or declining at the time of the exposure. As illustrated in figure 1, stress in the prenatal period affects the development of the hippocampus, prefrontal cortex, and amygdala, leading to programming effects. The differential effects of postnatal stress differ according to environmental exposure; for instance, maternal separation during childhood generally leads to increased secretion of cortisol, whereas exposure to severe abuse is associated with decreased levels of cortisol. From the prenatal period onwards, all developing brain areas are sensitive to the effects of stress hormones; however, some areas undergo rapid growth during key critical windows. From birth to 2 years of age, the developing hippocampus is most vulnerable to the effects of stress. By contrast, exposure to stress from birth to late childhood leads to changes in amygdala volume, which continues to develop until the late 20s.

Fig. 1. The life cycle model of stress. Reproduced with permission of the Nature Publishing Group from Lupien et al. [6].

      During adolescence, the hippocampus is fully organized, the amygdala continues to develop, and finally the frontal lobe undergoes important maturation. Consequently, stress exposure during this transition into adulthood can have major effects on the frontal cortex. Studies show that adolescents are highly vulnerable to stress because of pubertal changes in gonadic hormones and sensitivities of the hypothalamic-pituitary-adrenal axis that can persist into adulthood as potentiation/incubation effects. In adulthood and during aging, the brain regions that undergo the most rapid decline as a result of senescence are once again highly vulnerable to the effects of stress hormones. This leads to the manifestation of incubated effects from earlier life on the brain, known as manifestation effects or maintenance effects [6].

Lifelong brain changes ultimately diminish the organism’s ability to adapt, leading to subtle recalibrations in stress responsivity that could be used to detect disease trajectories [7]. According to the life cycle model of stress, regional volumes of these neurological structures in conjunction with biological signatures (e.g. hypercortisolism vs. hypocortisolism) can be used to predict differential risk profiles for specific psychopathologies (e.g. depression vs. PTSD) in adulthood as well as to inform when certain traumas might have occurred in early life [6]. While direct measurement of central nervous system substrates is costly and potentially invasive, indirect assessment using peripheral biomarkers routinely collected in blood draws can be used to infer AL levels. By interpreting this information in an alternative manner, the AL model proposes a temporal pathophysiological cascade useful for future early detection strategies for both physical and psychiatric