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Psychodynamic Psychiatry, 40(3) 469–480, 2012 © 2012 The American Academy of Psychoanalysis and Dynamic Psychiatry

KATZ ET AL. CHRONIC STRESS IN CHILDHOOD AND ALLOSTATIC LOAD

The Cost of Chronic Stress in Childhood: Understanding and Applying the Concept of Allostatic Load

Debra A. Katz, Ginny Sprang, and Circe Cooke

Abstract: This article explores the concept of allostatic load and its utility as an integrative framework for thinking about the impact of chronic stress on children and adolescents. Allostatic load refers to the failure or exhaustion of normal physiologic processes that occurs in response to severe, frequent, or chronic stressors. This persistent physiologic dysregulation may lead to sec- ondary health problems such as immunosuppression, obesity, atherosclerosis, and hypertension. Allostatic load can be measured and followed as a compos- ite index of a group of physiologic parameters which fall outside of a normal range. Although research regarding allostatic load in children is limited, this article explores relevant studies and identifies ways in which the concept of allostatic load can be used to broaden approaches to assessment, case formula- tion, and treatment in children. The concept of allostatic load may be of particu- lar interest to psychodynamic psychiatrists in recognizing the ways in which chronic stress and adverse childhood experiences lead not only to negative psychological sequelae but also to long-term health consequences including the possibility of premature death. It underscores the importance of monitor- ing patients’ physical as well as psychological health and thinking about the complex interrelations between the two.

The concept of “stress” is difficult to define and measure. It has been used to refer to a real or imagined threat to the psychological or physical integrity of an individual or to the impact of “stressors” (e.g., environmental, psychological, or biological events) on emotional, be- havioral, or physiologic functioning. Stress may be viewed as benefi-

Debra A. Katz, M.D., is with the Department of Psychiatry at the University of Kentucky College of Medicine.

Ginny Sprang, Ph.D., is with the University of Kentucky Center on Trauma and Children.

Circe Cooke, M.D., is with New River Valley Community Services, Blacksburg, VA.

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cial when it is of tolerable duration and leads to growth, mastery, and increased competence or as detrimental when it is severe, prolonged, or recurrent and overwhelms or impairs psychological or physiologi- cal coping abilities. What are the long-term physical and mental health effects of chronic stress on children? How can clinicians integrate an understanding of the impact of cumulative stress into their assess- ments, formulations, prevention efforts, and treatment plans? Research on factors such as trauma, attachment, gene-environment interactions, risk and protective factors, psychosocial adversity, and physical illness have broadened the scope of child evaluations, however, understand- ing and quantifying their impact, or the “stress” they cause, on a child’s current problems or potential to develop future problems has been a challenge. Psychiatrists are asked to evaluate psychosocial stressors as part of their multiaxial diagnostic assessment of each patient, however, the clinical usefulness, reliability, and validity of Axis IV assessment has been questioned (Skodol, 1991). In this article, we introduce the concepts of allostasis and allostatic load which we believe provide a helpful, integrative framework for thinking about the impact of stress on children and adolescents. Becoming acquainted with the concept of allostatic load allows clinicians to become aware of the ways in which chronic stress and adverse childhood experiences lead to long-term health consequences and contribute to premature death.

DEFINITIONs

Allostasis refers to the ability of complex physiological systems to “maintain stability or homeostasis through change” by adapting to physical, psychosocial, and environmental challenges (Sterling & Eyer, 1988). Changing internal and external demands lead to regulation of metabolic activities within multiple physiological systems such as car- diovascular, neuronal, immunologic, and endocrine. Allostasis involves adaptation by an organism to different situations by altering its inter- nal parameters in order to maintain normal function or stability. While homeostasis focuses on isolated feedback loops, allostasis emphasizes multiple interacting physiologic systems along with brain and nervous system control over the body’s responses. The concept of allostasis also includes the ability to anticipate stressors as opposed to solely reacting in response to them as well as the ability to show variability in response and complex responses through neurologic control of multiple physi- ologic systems.

Allostatic load refers to the failure or compromise of normal allostat- ic processes leading to chronic dysregulation of physiologic systems.

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Severe, frequent, or chronic challenges lead to cumulative strain over time on multiple organs and tissues which can be measured as allo- static load. For example, secretion of catecholamines and cortisol may be associated with healthy adaptation to an acute stressor (allostasis), but prolonged or severe stress may result in persistently abnormal cat- echolamine and cortisol levels. This chronic physiologic dysregulation, or allostatic load, may lead to secondary health problems such as im- munosuppression, obesity, atherosclerosis, and hypertension and has been associated with impaired physical and cognitive functioning and increased mortality in adulthood (McEwen, 2000; Seemen, McEwen, Rowe, & Singer, 2001).

Allostatic load involves the brain. The brain reacts to internal and external experiences by modulating physiologic and behavioral re- sponses and, in turn, is changed structurally and chemically by these experiences (McEwen, 2000). Psychological traits such as hostility or anxiety influence both the perception of what is stressful as well as the response to stress and therefore impact on allostatic load. Psychiatric disorders constitute a form of allostatic load through factors such as altered responsiveness to stressful experience, impaired social interac- tion, and abnormal mood as well as through their associated neuro- chemical and structural brain changes. For example, dysregulation of the hypothalamic-pituatary-adrenal (HPA) system, as is seen in depres- sion, has powerful and enduring effects on the brain and has been as- sociated with structural brain changes such as hippocampal atrophy (Videbech & Ravnikilde, 2004).

Genetics exert a powerful effect on both the propensity to develop psychiatric and medical illnesses, including the disorders associated with allostatic load, but may also influence allostatic load in indirect ways. For example, Kendler, Karkowski, and Prescott (1999) have shown that while stressful experiences play a key role in precipitating depression, individuals who are genetically at risk for depression actu- ally segregate themselves into higher risk environments. These find- ings illustrate the complexity of the gene-environment interaction and the multiple influences on the development of disease states associated with allostatic load. Behavioral and social factors may also constitute forms of allostatic load. Stress-related behaviors such as smoking, drinking, and overeating impact on health outcome and risk over time and social factors such as socioeconomic status have been shown to be strongly associated with morbidity and mortality. Finally, early adverse life experiences such as neglect or trauma profoundly and oftentimes permanently impact on brain circuitry involved in the stress response (Bremner, 2003) and contribute to the wide range of psychiatric and

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medical disorders that are commonly seen in this population in adult life (Anda et al., 2006).

hOW Is ALLOsTATIc LOAD MEAsuRED?

The physiologic parameters that reflect allostatic load differ across studies but are generally divided into primary mediators, such as nor- epinephrine, which regulate a variety of cellular events, and secondary outcomes, such as blood pressure, which reflect the cumulative effects of the primary mediators (Table 1; Clark, Bond, & Hecker, 2007). Tertiary outcomes are the actual disorders (e.g., hypertension, diabetes, athero- sclerosis) that arise from allostatic load. The allostatic load score is typi- cally calculated by summing the number of parameters which fall into the highest risk quartile. Thus if 10 physiologic indicators of risk are measured, the allostatic load score could range from 0–10. While there is not yet consensus on which of these parameters are most useful to measure in children, there is recognition that allostatic load provides a way of assessing physiologic “wear and tear” across multiple systems. By combining a broad range of biological risk factors into a composite score for allostatic load, clinicians have a comprehensive way to assess and follow a patient’s risk for a variety of stress-exacerbated diseases. This allows for assessment of risk in healthy individuals before the de- velopment of disease as well as an assessment of stress burden in pa- tients with multiple mental or physical health diagnoses.

REsEARch ON ALLOsTATIc LOAD IN chILDREN AND ADOLEscENTs

The Adverse Childhood Experiences (ACE) study clearly demon- strated the connection between negative psychological experiences in childhood with physical and mental health problems in adulthood. This large epidemiologic study showed that as the number of adverse childhood experiences increased, the risk for serious psychiatric and physical health problems in adulthood increased in a parallel fashion (Anda et al., 2006). This corresponds with exposure of the developing brain to physiologic mediators of the stress response with resulting dysregulation of multiple brain structures and functions. A longitu- dinal study of over 10,000 children followed from birth into middle adulthood demonstrated a correlation between internalizing and ex- ternalizing behaviors during childhood and increased mortality risk in

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adulthood thus confirming the serious health risks of childhood psy- chopathology (Jokela, Ferrie, & Kivimaki, 2009) Although these stud- ies demonstrate a correlation between a variety of adverse childhood experiences and symptoms and morbidity and mortality in adulthood, they do not delineate or follow the stepwise physiologic changes that occur in response to the chronic stressors studied.

Research on allostatic load in children and adolescents is limited but studies have correlated allostatic load with factors such as early menarche (Allsworth, Weitzen, & Boardman, 2005), household density (Johnston-Brooks, Lewis, Evans, & Whalen, 1998), violence (Murali & Chen, 2005), lower parent education (Goodman, McEwen, Bin, Dolan, & Adler, 2005), and adolescent alcohol use (Zimmerman, Blomeyer, Laucht, & Mann, 2007). Allostatic load has also been implicated as a mechanism in the development and perpetuation of eating disorders (Halmi, 2009). However, it is hard to separate out specific risk factors that lead to allostatic load when looking at the total stress burden on an individual child. Utilizing the concept of cumulative risk expo- sure, Evans (2003) found that allostatic load increased with elevated cumulative risk exposure in a group of rural elementary-school chil- dren. Cumulative risk included physical factors such as crowding, noise, and housing quality, psychosocial factors such as child separa- tion, family turmoil, and exposure to violence and home environment factors such as poverty, single parenthood, and maternal high school educational status. Children with greater cumulative risk exposure had more psychological distress, lower perceptions of self-worth, increased self-regulatory behavior problems, and learned helplessness. As these children were followed into adolescence (Evans, Kim, Ting, Tesher, &

Table 1. Measures of Allostatic Load

Primary Mediators Function

Cortisol Hypothalamic-pituitary-adrenal (HPA) activation

Dehyroepiandrosterone sulphate (DHEA-S) HPA antagonism

Epinephrine and norepinephrine Sympathetic system activation

Secondary Outcomes

Systolic and diastolic blood pressure Cardiovascular activity index

Waist-hip ratio or body mass index (BMI) Metabolic function index

High-density lipoprotein (HDL) & total-HDL cholesterol ratio

Atherosclerotic risk index

Glycosylated hemoglobin Glucose metabolism index

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Shannis, 2007), the effect of elevated cumulative risk continued to be correlated with increased allostatic load. A recent study has correlat- ed the chronic stress caused by childhood poverty with impairments in working memory in young adulthood (Evans & Schamberg, 2009). Chronic stress as measured by allostatic load in this study is thought to be an important factor accounting for the income-achievement gap. In a follow-up study of children with elevated cumulative risk who were followed into adolescence, maternal responsiveness was identi- fied as a protective factor in buffering the impact of allostatic load (Ev- ans, Kim, Ting, Tesher, & Shannis, 2007). This suggests that enhancing parent–child relationships, an important aspect of clinical work with children, can significantly impact on allostatic load. However, this also suggests that children who experience disruptions in caretaking and attachment or who experience unresponsive or harsh parenting may be even more susceptible to the effects of cumulative risk exposure and allostatic load.

Early relationships and security or insecurity of attachment may in- fluence vulnerability to allostatic load. In a study of over 100 mother- infant pairs (Hill-Soderlund et al., 2008), infants classified as insecure- avoidant showed greatest evidence of allostatic load as measured by sympathetic and parasympathetic responses to separation and reunion. Although all mothers demonstrated physiological changes with at- tempts to regulate their infant’s distress, mothers of securely attached infants showed the greatest physiological responses. This may seem surprising but these increased reactions, most evident during the last reunion episode suggest a greater attempt at interactive repair in this securely attached group of mothers. These findings illustrate the im- portance and impact of the earliest attachment relationships on physi- ologic responses to psychosocial stress in both infants and mothers and lend support to the importance of early intervention in clinical work with children. These findings should be interpreted with caution since further work needs to be done to correlate these findings in infancy with long-term negative health effects and allostatic load in adult- hood. However, it has been shown that adults with insecure-avoidant attachment patterns tend to suppress negative emotion and forego or avoid social support leading to increased risk for the development and continuation of physical health problems (Kotler, Buzwell, Romeo, & Bowland, 1994). The interconnections between attachment profile and physiologic changes leading to allostatic load have yet to be worked out fully, but these findings underscore the importance of early parent– child relationships in impacting on physical as well as psychological health and the tremendous effect that clinicians can have by addressing dysfunctional relationships early in life.

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hOW cAN cLINIcIANs usE ThE cONcEPT OF ALLOsTATIc LOAD?

Assessment

There is not consensus on how best to assess allostatic load in chil- dren, and research in this area is still in its infancy. However, there are a variety of ways the clinician can establish a baseline and follow pa- rameters associated with allostatic load. Measuring primary mediators such as overnight cortisol, epinephrine, and norepinephrine is general- ly not realistic. Assessing secondary outcomes such as blood pressure, waist-hip ratio, blood lipids, and glycosylated hemoglobin can easily be done in an office setting and may provide useful information about overall health status especially if followed over time. Psychiatrists or other mental health clinicians may not typically obtain this information about their patients, but it may prove useful both for following overall cardiovascular health status as well as in considering allostatic load. It is important to remember that it is not one set of measurements at one point in time that is important in allostatic load but rather the small, incremental changes over time that elevate a child into high risk groups for each parameter. This makes the need for long-term continuity of care especially important for patients at risk. Given the early stages of research on allostatic load in children, there is a need to gather data as to how often measurements should be made, which measurements are most helpful and how to understand the association of these measure- ments with long-term morbidity in children with psychiatric disorders.

case Formulation

The concepts of allostasis and allostatic load do not attempt to ne- glect important aspects of a child’s experience (e.g., intrapsychic, fam- ily, school) or to replace useful models of case formulation such as the biopsychosocial model or the “four Ps” model (predisposing, precipi- tating, perpetuating, protective). The goal of all case formulation is to develop a set of hypotheses about the etiology and range of influences on the patient’s presenting problems which will hopefully lead to a set of specific, individualized treatment recommendations.

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Utilizing the concepts of allostasis and allostatic load broadens and deepens the clinician’s formulation regarding the impact of external challenges that children confront and their potential for permanently dysregulating multiple physiologic systems leading to chronic impair- ment of mental and physical health. It allows the clinician to think more broadly about a variety of interventions, including those that seem somewhat simple or minor, and the significant impact they may have on long-term health. For example, low socioeconomic status, crowded living conditions, and single parenthood are not just social stressors but can be thought of as powerful contributors to allostatic load and over- all child health. Likewise, psychological stressors such as exposure to violence, multiple foster care placements, or harsh parenting carry risk not only for psychological well-being but may also impact on physi- cal health and morbidity from chronic illness through their impact on the neuroendocrine system and the brain. Dysregulation of the HPA axis from depression may not be recognized as a “biological” factor in a traditional biopsychosocial formulation but does lead to ongoing neurochemical and structural brain changes as well as to emotional and behavioral alterations that impact on the ability to respond adaptively to future stressors. It therefore becomes important as a clinician to think not just of typical stressors in each of the biological, psychological, and social domains but to think broadly and creatively regarding each of these and to pay careful attention to cumulative risk for all children. Stressors that have been associated with allostatic load in children that clinicians may not routinely think about might include physical crowding in the home, exposure to excessive noise, poor housing qual- ity, current or prior episodes of living in poverty, and parental high school dropout status. Insecure-avoidant attachment, early menarche, and frequent school absences due to illness have also been correlated with allostatic load in children. Much more work needs to be done to elucidate information that could be obtained from a clinical history that might reflect or be associated with allostatic load but current research suggests intriguing possibilities.

Risk and Intervention

Allostatic load reflects a confluence or convergence of risk factors and emphasizes the idea that cumulative wear and tear on the body over time results in a series of seemingly small physiologic changes (e.g., mild elevations in blood pressure, glucose, or lipids) that have the potential to impact on long-term health. Each small change in a physi-

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ologic parameter results in a small increase in morbidity and mortality, but, when changes in individual parameters are combined collectively over time, marked increases in morbidity, mortality, and psychosocial dysfunction are seen. Clinicians are in the unique position of being able to impact on allostatic load before these changes become fixed or ir- reversible. Psychodynamically oriented clinicians who typically work with patients over longer periods of time may have special opportu- nity to not only effect psychological change but to impact on allostatic load. Thus what may appear as seemingly small interventions such as referring a caretaker for treatment of depression or encouraging a child to participate in a sport to increase exercise and social interaction can have significant mental and physical health benefits. While enhancing maternal responsiveness is one factor that has been shown to reduce allostatic load (Evans, Kim, Ting, Tesher, & Shannis, 2007) other general interventions that may be helpful (but which psychodynamic clinicians may discount as important) include encouraging patients to reduce un- healthy behaviors such as smoking or overeating, ensuring adequate sleep, enhancing social connections, promoting cardiovascular health through exercise and diet, and working to enhance self-esteem and social success (McEwen, 2007). Children in out-of-home care may be especially vulnerable to allostatic load through the effects of early trau- ma, disrupted attachment relationships, and exposure to violence and substance abuse. It is especially important for clinicians to advocate for placement safety and stability and to minimize violence exposure and opportunities for retraumatization to reduce allostatic load in this vul- nerable population (Sprang, Katz, & Cooke, 2009). On a broader social level, allostatic load can be reduced by advocating for services and poli- cies such as access to health care, education, and housing that support children and families.

Physicians typically obtain physical examination and laboratory measurements as a way to assess potential risks or side effects of medi- cations, but it may be helpful as well to consider this data in light of allostatic load. Since allostatic load is affected by both psychological and physical stressors, a child’s weight gain and elevated blood glucose may be due in part to elevated stress hormones in response to psychi- atric illness or to psychological distress from recent events in addition to the primary side effects of medication. Psychiatric medications may exert a positive or negative impact on allostatic load. Neurotransmit- ter systems in the brain are altered by psychiatric medications which may, in the case of an illness like major depression, reduce allostatic load through reversal of adverse chemical or structural brain changes (McEwen, 2007). Allostatic load may be increased through the effects of medication on cardiovascular parameters such as blood pressure or

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on blood glucose or lipids. Because the origins of allostatic load are multidetermined and interconnected, improvements due to medication in one system do not always translate into improvements in other sys- tems or in overall allostatic load. Thus the issues regarding allostatic load and medications are complex and necessitate a full consideration of both psychiatric benefit and medical risk.

The concept of allostatic load offers advantages over a risk-resilience model. Instead of attempting to correlate individual risk and protec- tive factors with a vast array of psychiatric and medical diseases, al- lostatic load provides a way of measuring a composite index of stress burden on an individual—the allostatic load score—and allows the clinician to follow that score over time. In addition, some risks carry more weight than others and some periods of development are more vulnerable than others. There is significant evidence that early trau- matic experiences are especially important and may initiate a cascade of physiological and psychological processes that alter behavior as well as the structure and function of the brain (Bremner, 2003). These early experiences, which may be seen by psychodynamically oriented clini- cians as primarily having psychological impact, carry tremendous risk for the development and persistence of allostatic load into adulthood necessitating close mental and physical health follow-up.

Allostatic load does not differentiate between or privilege the social, psychological, or biological causes of stress burden on an individual but attempts in a rough way to quantify it. This allows the clinician to creatively decide how to intervene to lessen allostatic load. These inter- ventions may include ongoing psychotherapy or other forms of psy- chiatric treatment but may also include efforts not directly related to the problem at hand. For example, encouraging a parent to find appro- priate housing may significantly reduce household density, noise, and exposure to violence which may ultimately impact on allostatic load. These ideas validate some of the efforts clinicians make on behalf of patients that are outside the scope of typical professional interventions.

challenges and Future Directions

There are a number of challenges involved in attempting to uti- lize the concept of allostatic load with patients. Most of the research on allostatic load has been done with adults and much more work is needed to understand the development and progression of allostatic load in children. Further research is needed to operationalize which measures of allostatic load are most helpful in children, how to obtain

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these measures in busy clinical settings, which disease states correlate most strongly with different allostatic load profiles and how to man- age individuals with elevated scores. The association of allostatic load with larger societal issues such as socioeconomic inequality makes it important for clinicians to be aware of their own attitudes and preju- dices toward patients whose backgrounds may involve risk factors for high allostatic load. Because allostatic load is a composite index, the exact cause of an individual’s stress burden is not clear when they have an elevated score. This may therefore make it difficult to develop spe- cific interventions to reduce allostatic load. Much more work needs to be done to understand, delineate, and quantify the impact of multiple stressors on allostatic load.

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Debra A. Katz, M.D. Department of Psychiatry University of Kentucky College of Medicine 245 Fountain Court Lexington, KY 40509 [email protected]

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