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Association of Commonly Studied Personality Variables with the Stress and Immune Response

Permanent Link: http://ncf.sobek.ufl.edu/NCFE004181/00001

Material Information

Title: Association of Commonly Studied Personality Variables with the Stress and Immune Response
Physical Description: Book
Language: English
Creator: Stork, Benjamin
Publisher: New College of Florida
Place of Publication: Sarasota, Fla.
Creation Date: 2009
Publication Date: 2009

Subjects

Subjects / Keywords: Psychoneuroimmunology
Personality
Stress
Genre: bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Perception of the world around us is vital to the human experience of stress. This study directly quantified the effects of locus of control (LoC) and coping on the body's physiological response to stress. LoC when analyzed in combination with coping effectiveness presents a compelling and broadly applicable picture of how humans perceive life events. Individuals who express internal versus external LoC tend to have very different responses to stress. Physiological factors have come become increasingly important to the understanding of the stress response. Commonly studied is cortisol, whose levels are associated with both the chronic and acute affects of stress. Secretory Immunoglobulin A (sIgA) is useful in measuring immune competence relative to stress. Individuals with an external LoC and more effective coping skills tend to have reduced stress and increased immune competency compared to those with an internal LoC. Thus this association would likely hold for physiological indicators of stress. Strong correlations confirmed the association between LoC, coping and perceived stress, but associations with physiological variables were weaker. They were not significantly linked to LoC and coping but showed promise for future research.
Statement of Responsibility: by Benjamin Stork
Thesis: Thesis (B.A.) -- New College of Florida, 2009
Electronic Access: RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
Bibliography: Includes bibliographical references.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Local: Faculty Sponsor: Beulig, Alfred

Record Information

Source Institution: New College of Florida
Holding Location: New College of Florida
Rights Management: Applicable rights reserved.
Classification: local - S.T. 2009 S8
System ID: NCFE004181:00001

Permanent Link: http://ncf.sobek.ufl.edu/NCFE004181/00001

Material Information

Title: Association of Commonly Studied Personality Variables with the Stress and Immune Response
Physical Description: Book
Language: English
Creator: Stork, Benjamin
Publisher: New College of Florida
Place of Publication: Sarasota, Fla.
Creation Date: 2009
Publication Date: 2009

Subjects

Subjects / Keywords: Psychoneuroimmunology
Personality
Stress
Genre: bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Perception of the world around us is vital to the human experience of stress. This study directly quantified the effects of locus of control (LoC) and coping on the body's physiological response to stress. LoC when analyzed in combination with coping effectiveness presents a compelling and broadly applicable picture of how humans perceive life events. Individuals who express internal versus external LoC tend to have very different responses to stress. Physiological factors have come become increasingly important to the understanding of the stress response. Commonly studied is cortisol, whose levels are associated with both the chronic and acute affects of stress. Secretory Immunoglobulin A (sIgA) is useful in measuring immune competence relative to stress. Individuals with an external LoC and more effective coping skills tend to have reduced stress and increased immune competency compared to those with an internal LoC. Thus this association would likely hold for physiological indicators of stress. Strong correlations confirmed the association between LoC, coping and perceived stress, but associations with physiological variables were weaker. They were not significantly linked to LoC and coping but showed promise for future research.
Statement of Responsibility: by Benjamin Stork
Thesis: Thesis (B.A.) -- New College of Florida, 2009
Electronic Access: RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
Bibliography: Includes bibliographical references.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Local: Faculty Sponsor: Beulig, Alfred

Record Information

Source Institution: New College of Florida
Holding Location: New College of Florida
Rights Management: Applicable rights reserved.
Classification: local - S.T. 2009 S8
System ID: NCFE004181:00001


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A SSOCIATION OF COMMON LY STUDIED PERSONALI TY VARIABLES WITH THE STRESS AND IMMUNE RESPONSE BY B ENJAMIN STORK A Thesis Submitted to the Division of Natural Sciences New College of Florida In partial fulfillment of the requirements for the degree B achelor of Arts Under the sponsorship of Dr. Alfred Beulig Sarasota, Florida April, 2009

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Locus of Control, Coping, Stress and the Immune System ii Dedication For my parents who never stopped believing in me. Acknowledgments my t hesis. In particular I want to thank Kelsey for lending a helping hand with the logistics of the process, Max Ferretti for introducing me to the wonders of the human brain, and my parents again for their undying love and support.

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Locus of Control, Coping, Stress and the Immune System iii Table of Conten ts iv 1 Chapter 2: The Biology 29 5 0 2 48 Appendix A: Consent F Appendix B: Recruitmen Appendix C: Ove 56

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Locus of Control, Coping, Stress and the Immune System iv A SSOCIATION OF COMMON LY STUDIED PERSONALI TY VARIABLES WITH THE STRESS AND IMMUN E RESPONSE Benjamin Stork New College of Florida, 2009 ABSTRACT Perception of the w orld around us is vital to the human experience of stress. This study directly quantif ied the effects of l o cus of control (LoC) and coping on the siological response to stress. LoC when analyzed in combination with coping effectiveness presents a compelling and broadly applicable picture of how humans perceive life events. I ndividuals who express internal versus external LoC tend to have very different responses to stress. P hysiological factors have come become increasingly important to the unde rstanding of the stress response Commonly studied is cortisol, whose levels are associated with both the chronic and acute affects of stress. S ecretory Immunoglobulin A (sIgA) is useful in measuring immune competence relative to stress. I ndividuals with an external LoC and more effective coping skills tend to have reduced stress and increased immune competency compared to those with an internal LoC Thus this association would likely hold for physiological indicators of stress Strong correlations confir med the association between LoC, coping and perceived stress but associations with physiological variables were weaker They were not significantly linked to LoC and coping but showed promise for future research. Dr. Alfred Beulig Division of Natural Sci ences

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Locus of Control, Coping, Stress and the Immune System 1 Chapter 1: A Human Perspective on Stress Psychological and physiological factors are inextricably linked in the complex human response to stress. Whether chronic or acute, the way an individual responds to stress cognitively is integral to the physi ological response that occurs and should be utilized in validating the usefulness of any psychological measure with regard to stress. The reverse is also true as that physiological response is itself germinal to the psychological effects of the stressor. This bidirectional representation has come to be accepted as a model entities but different ways of conceptualizing the same processes. Psychological, neuroendocrine, and immuno logical factors involve so much crosstalk as to defy any reliable real world description as discrete factors, but some of the broadest concepts relating to psychological function are now serving a new and useful purpose in an increasingly integrated view o f psychoneuroimmunological (PNI) function in the body. While the term itself is unwieldy PNI represents an elegant restructuring how human health is studied. Disciplines which in the past have followed a trend of increasing specialization are now being re integrated in PNI as it explores the complex multilevel Locus of Control (LoC) and coping are seeing new use as they are linked to measurable physiological phenomena including acti vation of the Hypothalamic Pituitary Adrenal (HPA) axis and the metabolic processes which characterize this activation are also being linked to the immune response. This overall integration

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Locus of Control, Coping, Stress and the Immune System 2 of psychology, neurology and immunology provides fertile ground f or the development of a more unified model for human stress appraisal and its effect on immune competency. LoC and Coping represent personality traits central to the appraisal of stressful situations and given the integrative nature of the human body shou ld be highly correlated with both physiological measures of stress and immune function as well as their psychological analogues. Given the overwhelming amount of study dedicated to stress in humans and the generally broad and vague description thereof it is beneficial to fully explore both the modern theories of stress appraisal and their usage in current research. When a human is placed in a situation requiring creative use of limited physical and psychological faculties, what is broadly known as a stress ful responding to the purely environmental stressor. These experiences when taken together greatly affect how the cognitive processes involved in the assessment of and response to stress develop and function. Additionally, cognitive stress response when studied in the context of macro level psychological variables as well as common physiological indicators provides a useful top down schema in which to explain the relatio nship between prior experiences, commonly measured personality variables, and the physiological results of and response to stress. I n fact though many studies have sought to link specific environmental stimuli directly to coping mechanisms and physiolog ical responses, they have

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Locus of Control, Coping, Stress and the Immune System 3 been largely unsuccessful. Since i nternal and external attributional cognitive processes on the part of the individual involved must play a significant role in the human response to stress any unified theory of stress response mu st be built on measures able to directly tap cognitive processes. Appraisal theory (Sherer, 2001) is the currently accepted framework by which environmental factors such as event type and available coping mechanisms are linked to psychological factors suc h as perceived stress Appraisal is described in its most general sense cognitive interpretation one has regarding a potential stressor 1998) which is a construct both simple and ideally suited to mediate the interaction of psychological a nd environmental factors which are in the final analysis inextricably linked to the physiological response to stress. The appraisal theory framework has a long history including such prominent figures as Magda Arnold (Arnold, 1950) and Richard Lazarus as well as lesser known figures such as Gregory Maraon who are just now being recognized (Cornelius, 1991) Even William James and Carl Lange, considered to be among the forefathers of modern psychology have contributed to the framework. Though their contri butions pre date the model by half a century it was their conceptualization of emotion as an explanatory process for what they considered an instinctive or physiological process are at the heart of appraisal theory. While the James Lange theory of emotion has at times fallen into disfavor it has never been fully disproven, but rather has been combined with opposing theories such as the Cannon Bard theory of emotion developed by physiologists Walter Cannon and Philip Bard in such a way as to be compatible

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Locus of Control, Coping, Stress and the Immune System 4 w ith physiological finding that emotion results from complex bidirectional relationships between physiological factors and psychological states. This hybridization can be seen in recent research as emotional states have been shown to promote or preclude ph ysiological reactivity. Acting in the opposite direction physiol ogical reactivity due to stress as well as unrelated emotional states have been shown to allow misattribution of the cause of stress based on pre existing arousal (Taylor, Peplau, & Sears, 200 2, p. 103) Physiological reactivity due to improper assessment of or response to a stressor can manifest behaviorally and create negative consequences for the individual in question and those around them. Take as a hypothetical example a boy who is tre ated badly by those he wished to be friends with. He cannot turn his anger on them, because he desires their favor so when incidentally slighted by a boy whose friendship he does not desire he strikes out with anger or force disproportionate to the situat ion. This can apply to any individual who has been harassed repeatedly in a situation where he or she is unable to respond. When a small or incidental slight is experienced to which he or she can respond that response is disproportionately large due to ph ysiological arousal for which there was previously no functional outlet. It is also an example of ineffective or maladaptive coping which is readily explained utilizing a two factor theory of appraisal encompassing both cognitive and physiological factors. The preceding situation clearly demonstrates the links between emotion, physiological arousal and stress response and their impact on coping ability and appropriateness.

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Locus of Control, Coping, Stress and the Immune System 5 A theory linking these factors was proposed in its earliest complete form by Schac hter and Singer (1962) who in reviewing the literature in their day found that no discrete physiological correlates had been found to predict specific emotional states. Even today, years later the construct stands as a necessary linkage between the physio logical basis of emotional response to stress as no theory currently available can reliably predict how an individual will respond to stressful events utilizing only physiological and environmental measures. In fact recent attempts to narrow the context in which environmental factors are used to predict coping reactions, particularly as applied to illness related situations, hav e not improved their reliability (Mattlin et al. 1990). Rather, a single general excitation of the sympathetic nervous system seems to be associated with many discrete and varied emotions. Schachter and Singer reviewed a much older 1924 study by Maraon which found that while injection of adrenaline was likely to produce a psychological response, this response was only labeled as an emotion 29% of the time. Participants in his experiment were injected with adrenaline and then asked to introspect. Those who did experience an emotional response generally as if they were sad, or as if they were angry. In contrast, when the injection was paired with a sub threshold emotional stimulus (one which had evoked no emotion in earlier discussion) the psychological response was patently emotional in most cases. This seems to indicate that the phy siological component of emotional arousal requires a source to which it can be attributed before an individual experiences said arousal as

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Locus of Control, Coping, Stress and the Immune System 6 emotion. In addition a possible confound exists in that participants in study knew they were being injecte d with adrenaline which may have provided a cognition by which they could dismiss their physiological arousal without attributing an emotional state to the physiological arousal. Realizing that eliminating this variable could provide even stronger proof of their theory for emotional attribution Schachter and Singer propose d that if participants were covertly injected with adrenaline the participant would necessarily attribute an emotion to the physical feelings based on their environment and past experiences based on that particular into four experimental conditions. Three conditions involved administration of epinephrine, but all participants were under the impression they were participating in a drug trial for a new vision enhancing drug called suproxin as well as a placebo condition in which saline solution was administered. The conditions receiving epinep hrine were divided into three levels of knowledge about possible side effects. The first group was correctly informed of possible side effects, the second was not told anything about possible side effects and the third was given an inaccurate description of the side effects. The conditions in which epinephrine was administered had universally higher physiological arousal as measured by post injection pulse rate and palpitations but experienced that arousal in different ways. In those groups which were inf ormed correctly of the effects of epinephrine the participants reported little or no emotional arousal in

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Locus of Control, Coping, Stress and the Immune System 7 response to stimuli designed to provoke anger or euphoria. In contrast, those rmed of its side effects were far more susceptible to the emotional prompts, reporting higher levels of emotional arousal. While the ethics of this procedure may not be up to underlying physiological arousal. I n light of these findings they proposed that while autonomic arousal provided a substrate for internal emotional attribution, the form of that attribution was related to cognitive factors and interpreted in the context o f previous experience. Appraisal theory therefore holds that the process is in fact bi directional with physiological arous al being necessary but not sufficient for emotional arousal the form of which is determined by the life experiences and cognitive pro cessing strategies of the individual. The preceding would come to be known as the two factor theory of emotional arousal and while it has sparked intense debate regarding the validity of the underlying theory, it has undeniable explanatory power in cases of attribution and misattribution of physiological arousal and emotion (Cotton, 1981) and particularly in the underlying response to stress in human beings. Of course naming a factor does not change its nature and the black box ill be broken down to individual, measurable parts. The two factor theory of appraisal is often utilized to describe two commonly employed distinctions within appraisal theory, the primary and secondary appraisal. Primary appraisal describes how an indiv idual assesses the situation as it relates to them. This usually involves judgments as to the value placed on

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Locus of Control, Coping, Stress and the Immune System 8 the situation, the likelihood an outcome will affect the individual and what means he or she can bring to bear on the problem. Primary appraisal might be called a preliminary assessment, but not in a way that diminishes its importance. An has an immense effect on secondary appraisal, a crucial component of the cop ing respon se. In the secondary appraisal the individual using the knowledge of how a situation is likely to affect them reviews available coping options and based on cognitive factors such past experiences, control beliefs, and ideas about their own sel f efficacy decides which course of action is viable and appropriate. Contemporary research has embraced a framework in which these variables are utilized as explanatory factors for appraisal of stressful situations. Validated measures of Locus of Control, Self efficacy, available coping strategies, and in specific cases the value placed by the individual on the situation in question have been shown to be highly associated with appraisal judgments in research subsequent to the development of the original fra mework (Shaw, 1999), (Folkman, 1980) Most studies to date have explored the relationship of one or two of these variables in relation to appraisal and given the piecemeal nature of current research it is appropriate to examine each contributing factor bef ore attempting to integrate them into a unified picture. First and foremost due to its broad applicability is Locus of Control.

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Locus of Control, Coping, Stress and the Immune System 9 Locus of control is one of the cornerstones of appraisal theory and while it can be predictive even in its most general form i t has also been adapted to many specific situations. The internal/external continuum first proposed by Rotter in 1966 and the more explanatory Internal/Powerful Others/Chance continuum developed by Levenson in 1974 have been used by experimenters over the years to demonstrate how this aspect of explanatory style affects innumerable the degree to which participants attribute life events to internal and inherently controllable caus es or external and inherently uncontrollable factors. It is important at this point to note that in all locus of control research the variable is a continuum and that internal and external individuals are not static archetypes but often incorporate attrib utional beliefs from the opposite side of the spectrum to a lesser agree. different perceived sources of external LoC, powerful others and chance. T hese two perceived sources have pro ven to be useful distinctions particularly in health research (Shaw, 1999). As an example of the usefulness of the distinction, scoring high on the powerful others externality factor was correlated with more favorable outcomes in patients about to undergo major surgery (Shelley, M., and K. Pakenham 2007). Psychological preparation was more effective in those with high self efficacy, producing measurably more favorable outcomes among the high externality, high self efficacy group. T he demonstrated advanta ge of an external, powerful others locus of control as well as low situational self efficacy

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Locus of Control, Coping, Stress and the Immune System 10 shows that while internal locus of control is typically associated with more healthy coping, there are specific instances in which that is not the case. High scor es on very specific situations, including chronic disease. This brings to light a common misconception that individuals with internal loci of control are always at an advantage and highlights that locus of control is only one of many cognitive factors that work together to affect how an individ ua l reacts to a given situation. While the differentiation between chance and powerful others has been demonstrated as a useful distinctio n for these specific situations, it can also present an unnecessary complication of the variable in more generalized 1974 study have been shown to be moderately intercorrelated and as such are merely an interesting new way to look at LoC not a patent improvement over the Internal External (I Given this, several newer measures have been developed to address 66 locus of control scale while preserving the ( 1984 ) study reconceptualized the basis of the questions to couch them in terms of reinforcement or benefit to the individual. updated version include low item total score correlations (ITSC), the multidimensionality of the scale, the forced choice format of the original scale, inclusion of items that are not representative of the construct, the it em referents, and the heterogeneity of the external orientation. Low ITSC indicates that some

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Locus of Control, Coping, Stress and the Immune System 11 items were not reliably measuring what the entire instrument was intended to measure. This is a problem only in as much as it reduc es the power of the instrument b y diminishing its ability to detect either internal or external LoCs. This last complaint also segues nicely with the multidimensionality complaints with the total score may be tapping unintended issues by using item referents that are not simple enough and may be creating artifacts due to the wording of the scale itself which is over 40 years old. Finally, the forced choice format of the Rotter test has been replaced instea d with a Likert scale. Forced choice measures are notoriously unreliable as they are particularly susceptible to factors of social desirability and the fact that the choice is between two items that cannot be guaranteed to be symmetrical (Kanning & Kuhne, 2006). These improvements to the original scale not only make it a stronger measure, but update the language and the questions themselves to remain relevant in a different age. A logical concept to explore given a person with an internally oriented l ocus is that of self efficacy which indeed shares some characteristics of an internal locus of control, though it is a separately measureable phenomenon. Self efficacy is a modulator of behavior with far reaching effects. At its simplest it is an individ successfully carry out a chosen course of action (Taylor, Peplau, & Sears, 2002, pp. 113 114) choose the correct course of a

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Locus of Control, Coping, Stress and the Immune System 12 personal ideas about generalized self efficacy are believed to develop early based on the failures and successes of early life. These general ide a s of self efficacy apply to different domains of an ind efficacy in one domain is not necessarily predictive of low self efficacy in another. For instance, someone who always excelled at mathematics may have high self efficacy in that domain and related ones, but lack confiden ce in his or her ability in art, an unrelated domain. Individual conceptions of self efficacy are reinforced by comparison of performance in a given domain to self determined standards for that performance. In a domain where an individual feels a lower s ense of self efficacy, failure will reinforce avoidant coping whereas those with higher self efficacy will incorporate the reasons for failure into their coping strategy and try again (Bandura & Cervone, 1983) It is in situations where coping choices and efficacy is particularly crucial. Self important as it relates to coping due to its effect on the choice between emotional/avoidant c oping and action oriented coping The ability of an individual to cope with a given situation is an important factor in determining the stress that person will experience when presented with a novel, trying, or ambiguous situation. Coping however is not t ruly a single variable but involves both an inventory of available coping strategies, the ability to match the correct strategy to a situation, to learn from ineffective strategies and the belief that the strategies will be effective in resolving the situa tion. Thus efficacy is

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Locus of Control, Coping, Stress and the Immune System 13 germane to any possible assessment of coping skills. Of the two stages of appraisal, primary and secondary, self efficacy is of chief importance to the secondary or In this secondary appraisal stage, coping strategies can be broadly divided into three categories of unequal effectiveness (Taylor, Peplau, & Sears, 2002, pp. 448 452) Emotional coping is focused on emotio nal regulation, changing the way a stressful situation is perceived. An example would be individuals who deal with a breakup by convincing themselves that they are better off, or that their feelings for their former partner were never that strong. In con trast active coping methods are focused on changing the situation to remove or reduce the stressor. Finally avoidant coping involves disengaging behaviorally from a situation, often through the use of drugs or other addictive activities. These three copin g strategies exist simultaneously in every individual and can operate side by side. For instance in our breakup example, an individual who has suffered through the breakup of relationship may minimize the feelings towards their significant other and go to a bar to drink and forget where he or she will have the chance of meeting a new companion. The preceding example incorporates emotional, avoidant, and active coping methods respectively. Coping strategies as described above appropriateness to the situation in which they are utilized. An individual biased towards emotional coping, may miss opportunities for actively changing the stressful situation affecting them. Conversely a person who regularly engages in active coping may decompensate when faced with a situation he or she is unable

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Locus of Control, Coping, Stress and the Immune System 14 to affect in the slightest (e.g. cancer, loss of a loved one). Avoidant coping, seemingly the least effective of the lot still has a place and is a partic ularly effective method for dealing with short term stressful events as it expends minimal resources and is used preferentially when resources are scarce. Indeed linked to higher self efficacy and self esteem amongst urban youth sheddin g light on yet another variable, s ocietal influences. Sadly the influence of cultural variables fall outside the scope of this study which is limited to a small and culturally homogeno us group. Nev ertheless societal variables are an important determinant of both the cognitions involved in appraisal of stressful situations and the strategies chosen to confront them. In addition coping skills are dependent on external factors unique to each individua l as well including money, time to devote to coping, and social and emotional support. These factors must be The preceding factors are the major players in human appraisal of stress. It would s eem on the surface that a framework for stress appraisal and coping would necessarily be a fairly heterogeneous concept, but when explored further we find that is not the case. Significant commonalities are seen between the variables that underlie both th to it. W hile a factor may be perceived as internal by some and therefor e theoretically controllable, an efficacy and inventory of coping skills may modulate the degree to which they feel they are able to control that factor. This leads to the observed synergistic gating and modulatory effects

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Locus of Control, Coping, Stress and the Immune System 15 between LoC, coping, and self efficacy (Yakhnich, 2008). An excellent example of this modulation may be seen in the range of responses s een in cases of physical or psychological addicti on. Some individuals experience these situations as personally controllable events, and are more likely to take proactive steps to combat addiction, while others see them as inherently uncontrollable due to lack of coping mechanisms or low self efficacy beliefs regarding their ability to carry out coping mechanisms to which they do have access (Sklar & Turner, 1999). This modulation effect is also seen in a broader context as well When examined in the contex t of all 1992 study found locus of control to be a usefu l indicator of the stress perceived by patients however, it was determined that while necessary it was not sufficient to predict a ppropriat e and healthy coping, thus further demonstrating the gating effect of LoC on coping and stress appraisal in general. The interrelation of the psychological variables above and the overlap between instruments meant to measure them is a key factor in cont inuing research into stress. LoC, coping and self efficacy are important to any evaluation of a potential stressor and each helps to reveal useful information, but when utilized together as a descriptive framework they become far more powerful. Despite t his, there arises the need for a fully integrated framework which eliminates the overlapping aspects of each measure and introduces a more clearly defined concept of stress and more accurately describes the human response to it. Clearly each variable has p redictive power in its own right, but there are interaction effects between the commonly measured personality

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Locus of Control, Coping, Stress and the Immune System 16 variables which should be accounted for in any attempt to create a unified stress response measure. Testing issues aside, it is clear from the re search that cognitive appraisal of stress is predicted by personality variables and predictive of physiological responses and overall health when confronted with both acute and chronic stressors. Chapter 2 : Stress as a Physiological Process The physiologic al response to stress is linked to both psychological and immunological r esponses by two main neuroendoc rinological pathways. Acute response to stress is largely mediated by the Sympathetic Adrenomedullary system (SAM), while the longer term reactions to stress are the linked to the Hypothalamic Pituitary Adrenocortical (HPA) axis. W hile often represented as discrete systems they are better evaluated as complimentary components of an overall stress response system due to the interdependent nature of their activation and commonalities in their targets The overarching mechanisms of the system have been well established in the last two decades and while nuances continue to emerge, little has been discovered which changes the overall system. The SAM system is important as a mediator of acute stress response, and will be explored as it relates to HPA activation, but since this study is concerned with stable global effects of personality traits on immune response, acute stress falls outside the scope of this pro tocol. Both systems are intrinsically linked to an

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Locus of Control, Coping, Stress and the Immune System 17 and bottom up perspective with communication taking place between higher brain areas and the smallest immune constituent in a bidirectional manner. As the mechanism by which the body compensates for long term stress, the HPA axis is essential to understanding the human response to physical, psychological and immunological stressors. Since the crosstalk of this system makes it essentially cyclic, one starting point is as good as another, and by the top down convention the cycle begins in the paraventricular nucleus of the hypothalamus. This region is particularly sensitive to monoamine neurotransmitters associated with mood c hanges in humans such as serotonin (5 HT) and noradrenaline (Evans, Hucklebridge, & Clow, 2000) It is interesting to note that the monoamine cascade which initiates PVN activity is very similar regardless of the nature of the stressor. Psychological and immune stress in particular present very similar monoamine interactions. This has led to speculation that psychological stress responses may have co opted an evolutionarily older immune stress response system (Koolhaas, 2008) When activated continuous ly by this cascde the PVN releases two potent stimulatory hormones in response to stress (Ader, Felten, & Cohen, 1991) Arginine Vasopressin, which is secreted by the magnocellular region of the PVN, is a potent diuretic that also has neuroendocrine functi ons controlling blood pressure and aggression. More importantly, it functions synergistically alongside the second hormone secreted by the PVN during HPA activation: corticotrophin releasing hormone (CRH). Both CRH and arginine vasopressin are released i nto

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Locus of Control, Coping, Stress and the Immune System 18 the hypothalamo hypophyseal portal system which is a vascular connection between the hypothalamus and the pituitary gland. In addition CRH also acts upon the Locus Coeruleus causing sympathetic nervous system (SNS) arousal characteristic of SAM activa tion, demonstrating the overlapping nature of the systems. When CRH and arginine vasopressin arrive at the anterior pituitary they bind to receptors which stimulate the next step in the cascade. Upon binding CRH and arginine vasopressin the anterior pitu itary secretes it makes its way to the adrenal cortex atop the kidneys. The adrenal cortex can be divided anatomically into three discrete areas, two of which respond strongly to ACTH. The outermost area called the zona glomerulosa is not responsive to ACTH and primarily secretes mineralocorticoids which are not si g nificantly involved in the stress response. The zona fasiculata which resides interior to the zona glomerulosa is responsive to ACTH and produces one of two extremely important stress hormones: cortisol. The innermost area, the zona reticularis, produces a second and equally important stress hormone known as dehydroepiandosterone (DHEA). It is important to note that cortisol and DHEA are not stored within the adrenal cortex, but produced on command by the cortex in response to HPA activation. This demonstrates the nature of the system as a long term response mechanism since levels of cortisol and DHEA increase slowl y following activation and do not change transiently in response to most stimuli. In fact it often proves difficult for researchers to induce HPA activation experimentally. For instance, while paced

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Locus of Control, Coping, Stress and the Immune System 19 mental arithmetic is an effective means of activating t he SAM system, it has no effect on levels of cortisol on the time scale involved and activates the HPA axis only in individuals who have extreme phobia of mathematics or time pressure. In fact, while cortisol and DHEA vary significantly on a diurnal basis they are generally very stable measures of chronic stress if those measures are taken at the same time each day. Activation of the HPA axis is a critical trigger in producing hormones that prepare the body for long term coping. Once these hormones are secreted into system circulation their concentration and activity lead to wide ranging effects on all bodily systems including the immunoregulatory machinery with which this study is concerned. There are two general types of immune function, innate and a daptive which though useful in a categorical sense are truly one interrelated system. Innate defenses are the first called into action and have a static set of conditions to which they can respond. This system is composed of several levels and the first a pathogen encounters is the simple but effective physical barrier presented by the skin, mucous membranes and hair. Skin and hair present surfaces which are impermeable to most pathogens, while the mucosal surfaces are a more complex story which will seg ue well into the internal mechanisms of innate immunity. The mucosal membranes represent a combination of physical barrier and active innate immune system. Mucosal membranes in humans represent site s at which the body must exchange materials with its envi ronment; this includes the digestive and respiratory tracts. Proper function of these exchange surfaces is critical to human survival, but they are necessarily more vulnerable to

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Locus of Control, Coping, Stress and the Immune System 20 infection, offering a more direct means of entry into system ic circulation f or a pathogen. This is why the mucosal membranes combine physical and active innate immune responses. The physical barrier of the mucosa slows the progress of infectious agents, and is consta ntly removed and replaced by ci liary action, but contained in the mucosa are active cells called phagocytes which seek out and destroy matter not recognized as part of the host organism. Phagocytes exhibit the most important trait common to both the adaptive and innate immune system, self nonself discrimination. The fi rst line of immune defense once a foreign invader has breached the subtypes of white blood cells that recognize foreign cells and envelope and consume them in a process known as phagocytosis. Phagocytosis stemming from the Greek word phagein (meaning to eat or devour) and from the Greek word kutos (meaning hollow vessel) is the process by which a ce ll engulfs, isolates and subsequently breaks down another cell or other foreign matter. The process is multipartite and varies from cell to cell; however a rough order of operation is generally observed. First, a phagocyte recognizes epitopes known as pat hogen associated molecular patterns (PAMPs). These patterns include, but are not limited to bacterial cell surface proteins, lipopolysaccharides, bacterial flagellin, lipoteichoic acid, and peptidoglycan. In viral recognition PAMPs often include double

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Locus of Control, Coping, Stress and the Immune System 21 stranded RNA and unmethylated CpC motifs consisting of Cytosine phosphate Guanine groups which characterize certain viral RNA. Markers of this nature are recognized by Pattern Recognition Receptors (PRRs) which span the membrane of phagocytic cells and inc lude primarily T oll like receptor and the mannose receptor. The toll like receptor is the more prevalent of the two and is found in all phagocytic cells. It is interesting to note that the TLR receptor is found in vertebrates as well as invertebrates and is evolutionarily categorized as one of the earliest immune responses. The mannose receptor is less prevalent across phagocyte types and is found only in macrophages and dendritic cells. It is a cell surface receptor much like TLR but bonds specifically to the carbohydrates found in microbial cells (Apostolopoulos & McKenzie, 2001). Once a pathogen is recognized, the phagocyte approaches and envelopes it through a process known as endocytosis. The pathogen is kept in a separate membrane bound compartme nt in the phagocyte until that compartment combines with a lysozome which contains radical oxides and proteolytic enzymes capable of lysing and digesting the invader. Phagocytes can further be differentiated into classes such as monocytes, macrophages, de ndritic cells, neutrophils, basophils and eosinophils all of which have specific functions in both innate defense and mobilization of the adaptive immune system. Where the innate defenses of the human body are concerned however Initial immune response is d innate immune system to be present in large numbers, correctly identify bacteria and effectively phagocytose foreign invaders. The response of macrophages

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Locus of Control, Coping, Stress and the Immune System 22 and neutrophils in particular is important to the activ ation of the final component of the innate immune system, th e comple ment system. Macrophages and neutrophils at the site of injury and inflammation release cytokine messengers which act on the liver to produce acute phase proteins. These proteins interac t with C1q, the first protein in the compliment cascade activating the compliment body. The end result of each pathway is production of membrane attack complexes (MACs) that punc ture the cell membrane of invading pathogens, destroying the m. The comple ment system is categorized in the innate immune system because its target specificity never changes, but it is crucial measure in keeping pathogens at bay while adaptive immunity is b eing ramped up (Janeway, 2005). Phagocytic cells represent a bridge between innate and adaptive immunity and their high TLR expression is particularly important to proliferation of the adaptive immune response as activation of TLR proteins by a pathogen i nduced nuclear factor kappa beta ( NFKB ) and membrane associated protein kinase (MAPK) signaling cascades is essential to the upregulation of cytokines and other intercellular messengers. The release of these messengers stimulates inflammatory response at the site of detection as well as activating the adaptive immune system demonstrating the unified nature of the immune response. 2006).

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Locus of Control, Coping, Stress and the Immune System 23 The adaptive immune response is slower to develop than the innate responses, but is far more precise a nd effective. As phagocytes encounter and destroy pathogens, some known as antigen presenting cells (APCs) display unique features of the destroyed invaders on their own cell membrane. An example of this class of cell is the dendritic cell whose primary purpose is to phagocytose invaders then migrate to lymphoid organs such as the spleen or lymph nodes. template for the production of lymphocytes which can directly target t he invading pathogen. This proliferation occurs by a process known as clonal expansion in which lymphocytes are produced with varying antibody targets and only those incomplete remova l of self targeted cells during clonal expansion is one cause of autoimmune disorders in humans. When exposed to the antibody on the APC cell these inactive lymphocytes again proliferate into a new generation able to target the invading pathogen precisely. At this point the adaptive immune system can trend towards two diametrically opposed responses, T helper 1 (Th1) or T helper 2 (Th2). The functional distinction between Th1 and Th2 immune responses is far more accurate and useful in predicting real world events than the largely artificial distinction between innate and active immune responses. Which response is favored (Th1 or Th2) depends on the interaction between T helper cells and cytokine messengers released at the site of the infection, as well as t he pattern of autonomic reaction to the stressor. Th1, also known as cell

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Locus of Control, Coping, Stress and the Immune System 24 targeted against parasite initiated by an increase in interferon gamma (IFN alpha (TNF integrative system. These increases can be amplified by psychological factors as is seen in the case of in cases of acute social stress induced anxiety. Stress of this nature has been shown to lead to a dominance of Th1 immune function (Maes, Van Gastel, Delmeire, Kenis, Bosmans, & Song, 2002) and demonstrates the crucial role the physiological correlates of psychological stress play in the immune response. When Th1 is dominant inflammation is more prevalent, macrophages are more active and aggressive. At the same time cytotoxic cells such as natu ral killer (NK) cells are allowed to attack host cells displaying signs of infection. Cell mediated immune response also upregulates cytokines which affect the brain directly including interleukin 1 (IL 1) production by macrophages. IL 1 is a cytokine mes senger which also has the effect of being a peripherally acting neurotransmitter known to induce sickness behavior in humans (Vollmer Conna, Fazou, Cameron, Li, Brennan, Luck, Davenport, Wakefield, Hickie, & Lloyd, 2004) IL 1 cannot pass the blood brain barrier to stimulate the central nervous system directly, but instead acts on the vagus nerve which in turn causes release of an IL 1 analogue inside the blood brain barrier. When IL 1 is secreted in the brain it induces behavior characteristic of energy conservation during illness including reduced sexual behavior, food searching, and increased

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Locus of Control, Coping, Stress and the Immune System 25 is commonly known as a fever. This common psychoneuroimmunological interaction is an example of the bottom up component of bidirectional communication between these functional systems. A second and opposite example with respect to cell mediated immunity is upregulation of IL 2. IL 2 was initially thought to be a component of the cyto kine cascade which initiated Th1 cascade, but was found to be produced by Th1 lymphocytes and act centrally to stimulate the Locus Coeruleus, increasing neuropeptide Y secretion which downregulates aspects of Th1 such as cytotoxic activity which are relate d to autoimmune inflammatory disorders. It is interesting to note that this is accomplished while simultaneously inducing sleepiness in humans since the body is better equipped to implement the Th1 immune responses during sleep, demonstrating again the deg ree to which sensations humans experience on a daily basis are linked to immune and neuroendocrine function at the most basic level. The Th2 or humoral immune response is primarily governed by B Cells rather than the T cells of Th1 and in contrast to Th1 i s primarily oriented towards the production of antibodies. Antibodies or Immunoglobulins are a product of adaptive immunity in B lymphocytes responding to contact with an antigen. They bind to the surface of foreign invaders to make them more recognizable to phagocytes in a process known as opsonization. Opsonization also activates a targeted complement cascade against the cell in another example of innate/adaptive immune system cooperation. The Th2 response is responsible upregulating production some class es of phagocyte such as eosinophils which

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Locus of Control, Coping, Stress and the Immune System 26 are particularly suited to utilizing antibody targeting to kill parasites and larger invading organisms. Prolonged Th2 dominance has its own risks however as it can lead to oversensitization of the immune system ca using allergic atopic disorders (Evans, Hucklebridge, & Clow, 2000). An example of Th2 dominance can be seen in students under academic stress with pre existing allergic disorders such as asthma. Higher levels of cortisol associated with chronic stress pr omote Th2 dominance under chronic academic stress and cause an increase in allergic reactions. Academic stress was associated with lower IFN 2 circulation as well as increases IL 6 concentration when measured from stimulated mononuclear cell cul tures of whole blood (Kang & Fox, 2001). Top down influences are not the only psychoneuroimmunological interaction however as recent research has established a role for cytokines in psychological disorders study found a positive correlation between IL 1, IL 6 and C reactive protein (an acute phase protein produced by the liver) and depression. In addition, these cytokines in particular and immune system dysregulation in general have been proposed as a link between psychological manifestations and health complications. It is important to note that these associations are bidirectional, providing strong evidence for top down and bottom up effects of stress on both physical and psychological health. The bidirec tional nature of psychoneuroimmunological interaction has some interesting implications for the effect of environmental factors on the immune system as well.

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Locus of Control, Coping, Stress and the Immune System 27 A recent study carried out at the University of Wisconsin, Madison has been using infection of pigs by a whipworm parasite to combat multiple sclerosis. Researchers believe the whipworm causes Th2 activation mediated downregulation of Th1 cytokines, effectively reducing and in some cases eliminating the Th1 dominance which is the likely cause of ma ny autoimmune disorders. There is a body of research that suggests the abiotic environment in which children develop may lead to a dysregulation of the Th1/Th2 balance which leads to Th1 dominance. This seems to be supported by evidence showing a lower pr evalence of autoimmune disorders and depression (both Th1 mediated) in developing countries (Brody, 2009). Given the associations between psychological factors and immune responses, a great deal of research has been conducted which explores the ways in which the immune system interacts directly with the complex neuroendocrine stress response. The two end products of the HPA axis, cortisol and DHEA, are the primary effectors with respect to top down neuroimmune communication and stress. Cortisol is The T h1/Th2 trend is a spectrum rather than a decision point and both processes are usually operative simultaneously to a greater or lesser degree. This complexity is compounded by the inhibitory effects that cytokines from one cascade have on the opposing one For instance, IFN expression via downregulation of IL 4 production. Several of the Th2 associated cytokines exhibit inhibitory effects on the Th1 cascade as well with IL 4, IL 10, and IL 13 suppressing Th1 immunity by downregulating IL 2 and IFN

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Locus of Control, Coping, Stress and the Immune System 28 production. The Th1/Th2 balance is a delicate one affected by many factors from distal (Inherited predispositions, developmental conditions) to proximal (cytokine releases, neuroendoc rine stres s responses). The bidirectional interactions between immune function and psychological manifestations, which act via neuroendochrine communication, present a complex framework which can even opment in an environment with no opportunity for Th2 activation could potentially predispose that child to immunological dysregulation and subsequent depression due to abnormally high levels of IL 6, which is also associated with atherosclerosis and other cardiovascular problems. The delicate balance between the two processes and the degree to which they can be affected by environmental and psychological factors clearly delineates a paradigm by which understanding stress appraisal is paramount to elucidatin g the system as a whole. Unfortunately, in small scale research many traditional measures of neuroendocrine function (serum Cortisol etc) and immune function (blood lymphocyte and antibody levels) are both too expensive and beyond the skill of beginning researchers. In lieu of these traditional measures salivary assay of related metabolites has become the standard for quick, cost effective research into stress and immune function. In addition, salivary sampling has the benefit of avoiding the increased sympathetic activation many people display in response to needles. This response can be attributed to both psychologically condition ed fear of needles as well as a generalized physiological response to injury. Measures of cortisol the relationship of whi ch to stress has been elucidated

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Locus of Control, Coping, Stress and the Immune System 29 above have been shown to be linearly correlated with its own metabolite in saliva. A measure of immune competence that has become popular in recent years is secretory Immunoglobulin A (sIgA) which is present in all mucous m embranes in the human body (Wetherell & Sidgreaves, 2005) sIgA is the most prevalent antibody found in mucous membrane secretions and is unique in that serum levels are very low and not of primary relevance since sIgA is utilized as a first line of defen se. This makes sIgA particularly suited to salivary analysis in stress as basal levels of sIgA have been shown to be linked to basal Cortisol, HPA reactivity and most importantly immune function. In fact, while they are reactive to transient stressors to greater or lesser degrees, a basal level has been shown to be predictive of stress related susceptibility to ill health (Volkmann, Geffen, & Weekes, 2006) These measures can be utilized to quickly and easily ascertain both HPA activation and immune compet ence as they are related to commonly measured personality variables related to stress. Links between measurable psychological variables and physiological variables can be utilized both to further understanding of illness and design both behavioral and pha rmacological interventions. To further this goal, relationships between personality traits and immunological and neuroendocrine measures were explored in this pilot study. Chapter 3: Stress and Disease The measures explored both psychological and physi ological are not abstract constructions. They are useful indices of factors that affect health, and

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Locus of Control, Coping, Stress and the Immune System 30 though they are indirect, they represent biological processes that can influence many types of illness on one level or another. A significant number of re al world illnesses have been directly linked to the effects of stress whether as a causative factor or in a smaller contributing role. First and foremost, Coronary Heart Disease ( CHD ) has been consistently and strongly associated with stress. One 1991 stud y followed 2000 men with no history of Myocardial Infarction ( MI ) over 12 years and analyzed the prevalence of CHD as related to stress (Rosengren, Tibblin, & Wilhelmsen, 1991). Chronic stress in the past 1 5 years among the sample was found to be signifi cantly associated with coronary artery disease. It is possible that the risky behaviors (alcohol and tobacco consumption, overeating) associated with stress could be a third variable in this case, but when controlled for they reduced the association only slightly. This seems to indicate that the physiological processes associated with stress, the ones being measured in this study are the primary causes of MI and associated coronary artery disease, and are exacerbated by maladaptive coping measures often as sociated with stress. Indeed several studies of work related stress have linked the same psychological factors being measured in this study to CHD. Individuals working in high demand environments combined with low control, which could be conceptualized as a forced external locus of control, are at much greater risk for developing CHD (Haan, 1988, Karasek, 1979). In addition the individuals in these studies who remained in unsatisfying highly stressful jobs likely had poorly developed coping skills or low s elf efficacy based on their inability to move up within the company or move to a more fulfilling job elsewhere. Alternatively their

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Locus of Control, Coping, Stress and the Immune System 31 perceptions of the workplace may in fact have been the root of the stressful nature of the work, rather than any factor inh erent to the work itself. A 1993 study found that stress could be reduced to a generalized anxiety score and still be relevant (Markovitz, Matthews, Kannel, Cobb, & D'Agostino, 1992) Following a group of individuals for 20 years they found that anxiety was predictive of hypertension independent of many predisposing factors including, age, obesity, glucose intolerance, smoking and alcohol intake. More recent studies have linked immune substituents to possible factors in CHD such as atherosclerosis. One r ecent theory suggests that during stress, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to formation of atheromatous plaques in the art erial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The first step of atherogenesis is the development of fatty streaks, which are small subendothelial deposits of oxidized cholesterol and monocyte derived macrophages. The exact cause for this process is unknown, and fatty streaks may appear and disappear. LDL in blood plasma poses a risk for cardiovascular disease when it invades the endothelium and becomes oxidized. A complex set of biochemical reactions regulates the oxidation of LDL, chiefly stimulated by presence of free radicals in the endothelium or blood vessel lining. The initial damage to the blood vessel wall results in a "call for help," an inflammatory response. Monocytes (a type of white blood cell) enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction

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Locus of Control, Coping, Stress and the Immune System 32 of factors such as VCAM 1, which recruit circulating monocytes. The monocytes differentiate into macrophages, which ingest oxidized LDL, slowly turning into large "foam cells" so described because of their changed appearance resulting from the numerous internal cytoplasmic vesicles and resulting high lipid content. Under the microscope, the lesion now appears a s a fatty streak. Foam cells eventually die, and further propagate the inflammatory process. There is also smooth muscle proliferation and migration from tunica media to intima responding to cytokines secreted by damaged endothelial cells. This would cause the formation of a fibrous capsule covering the fatty streak. Elevated soluble ICAM levels demonstrated increased vascular inflammation in atherosclerotic patients. RNA from circulating CD4+ T cells, CD14+ monocytes, lipopolysaccharide stimulated monocyte s, and macrophages was subjected to genome wide expression analysis. In CD14+ monocytes, few inflammatory genes were overexpressed in control patients, while atherosclerotic patients showed overexpression of a group of Krppel associated box containing t ranscription factors involved in negative regulation of g ene expression (Schirmer et al., 2008). This is just one possible pathway in a single disease among many known to be mediated by stress and is a strong exemplar of the ability of stress to predispose individuals to disease. Not all diseases are affected by stress in the same way however. Cancer for instance, another disease known to be highly associated with stress, displays a different relationship to stress than CHD. ng the Minnesota Multiphasic Personality Inventory ( MMPI ) showed a twofold increase

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Locus of Control, Coping, Stress and the Immune System 33 in cancer deaths among depressed individuals (Shekelle, Raynor, Ostfeld, & Garron, 1981) Another study involving 7000 individuals however looked at mortality from cancer a s compared to the incidence of cancer related to stress. In the case of cancer it appears that while incidence of cancer in individuals is unrelated to stress, the mo rtality rate due to cancer is highly associated with stress both before and after the ons et of cancer (Zonderman, Costa, & McCrae, 1989). Recent work has linked stress and poor cancer survival to flattened cortisol responses in individuals fighting cancer (McNamara, 2006). These individuals, who also rate highly on depression measures experie nce dysregulation of the HPA axis which in turn affects the immune response to cancer resulting in lower Natural Killer cell activity. Since NK cytotoxic activity is a necessity when the body fights cancer this is associated with increased morbidity in ca ncer patients. Diseases such as CHD and cancer which both have autoimmune components are the most highly associated with measures of stress. In the same vein, infection by foreign invaders such as bacteria, parasites and viruses can also be influenced b y stress and the immune response to it in real world scenarios. A 1992 study found a significant association between life events, their perceptions and response to an experimental rhinoviral challe nge (Stone, Bovbjerg, Neale, Napoli, & Valdimarsdottir, 19 92). In it p articipants who developed symptoms of cold following the challenge reported greater number of BOTH positive and negative life events This indicates that as far as stress is concerned it is often the perception of a stressor rather than the c ategory or

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Locus of Control, Coping, Stress and the Immune System 34 strength of the stressor itself that is linked to physiological effects. In the previous study, it is clear that lability of stressor response and mood are responsible for an increase in overall physiological stress response, this decreases the resources available to the body to respond to infection and makes it more likely that infection will colonize and develop into a full blown clinical cold. A similar study helps narrow the scope of this emotional and physiological reactivity by linking per ceived stress and life events to different aspects of infection and immune response (Cohen, Tyrrell, & Smith, 1993) They found that perceived stress and negative affect predicted susceptibility to infection while life events predicted the development of a clinical cold and associated sickness behaviors. Many of these studies, though conducted before the analysis of stress related metabolites was common are still useful due to their large sample size and longitudinal nature and help demonstrate not only th e importance of stress as it relates to real world disease, but the heterogeneous yet interrelated nature of the concept of stress itself. Additionally, they shed light on the possibility that stress can affect different aspects of disease dependent both u pon the type of disease, its course and the type of stress being studied. Finally, they relate stress as a concept to specific, reliable, stable personality traits. These traits, when studied in association with the physiological responses they are known to predict can be incorporated into a framework for understanding and treating disease. This framework, incorporating cognitive behavioral aspects of stress and strong associations with immune and neuroendocrine function into the

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Locus of Control, Coping, Stress and the Immune System 35 treatment of illness may prove to be extremely useful in situations where traditional medical intervention is not yet available. This study sought to further quantify the relationship between LoC, coping strategies, and physiological indicators of stress and immune function such as experimental method chosen due to budgetary constraints. In this method participants were tested for both physiological and psychological factors associated with stress in one session and the relationship explored based on the data from the single session. The associations between physiological variables and psychological variables were examined as they related to perceived stress and perceived mental and physical health. Meth ods Participants Participants were 15 (6 male and 9 female) undergraduate students from New College of Florida chosen by convenience sampling using promotional fliers (see appendix B). Only 15 participants were tested for salivary metabolites due to time and budgetary contstraints. Participants were all volunteers over the age of 18 with no conditions which could affect their endocrine or immune responses, such as steroid use or illness. They were asked to refrain from alcohol and other substance use fo r a period of 24 hours preceding the experiment and to ingest no more than one caffeinated beverage prior to the salivary collection on the day

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Locus of Control, Coping, Stress and the Immune System 36 of the experiment. In addition, to avoid blood contamination of saliva, participants were asked to refrain from brushing teeth within 45 mins preceding collection and having dental work performed within 24 hours preceding collection. Nicotine and over the counter drug use were documented but did not disqualify participants. Restrictions were the result of Salimetr ics sampling guidelines for cortisol and secretory Immunoglobulin A as stated in their accompanying literature ( Correcting Salivary Analyte Concentrations for Saliva Flowrate 2008) and ( Collecting Unstimulated Whole Saliva Samples by Passive Drool From Hu man Subjects (ages 5+) 2008 ) Protocol The experiment was carried out in a large classroom at New College of Florida Most students were tested on the same day between 1600 and 1800 hours while some students with scheduling conflicts were tested between 1 600 and 1800 hours on a different day in order to minimize the diurnal variation in sIgA and cortisol levels. Once the experiment was satisfactorily explained and the consent form (Appendix A) signed, the participants were each given a saliva cryovial wit h a numerical identifier on it and asked to use the number to identify themselves on all forms. A random number generator was utilized to choose which participants would be tested for salivary metabolites. Participants were also instructed to record their identifier on their copy of the consent form in order to obtain their test results from the experimenter upon completion of the experiment if so desired. Before saliva samples were taken, participants w ere asked to rinse their mouths

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Locus of Control, Coping, Stress and the Immune System 37 with water and wait t en minutes to eliminate any possible contaminants from the saliva and ensure that salivary secretions reflect a basal state rather and any events which may have occurred before the experiment Saliva was collected using the passive drool protocol provided by Salimetrics in which participants were asked to think of a food they enjoyed and drool through a two inch length of plastic straw into their respective cryovials, being sure to obtain at least 1ml of saliva per participant. The order in which the sali va samples and self reports were taken w as counterbalanced to eliminate order effects. Half (ID #s ending /w odd #) had the salivary samples taken first while the remaining half(ID#s ending /w even #) completed the self report measures and then collected salivary samples The order in which the self report measures were administered w as counterbalanced across the two groups. After the last test ha d been administered the participant was allowed to choose a gift from a selection of small toy s Each sample w as preserved in its own cryovial in a 20 o C freezer until all samples were collected. The samples w ere then shipped overnight to Salimetrics for testing. Each sIgA sample was tested twice and the values averaged to ensure reliability since while the rel iability for the salivary cortisol assay is high (0.91), the salivary IgA measure has a lower reliability at (0.64). The self report measures were scored by the experimenter and the data transposed along with the physiological data into a S PSS 17 data set Data w as coded using the numerical identifiers supplied and no personal identifiers were used Samples sent away for testing w ere only identifiable by this numerical code. Following the experiment the data file was encrypted and will be retained

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Locus of Control, Coping, Stress and the Immune System 38 for 3 years as per New College institutional review board policy Title 45 CFR Part 46 § 46.115(b) and will be destroyed immediately thereafter using Fileshredder ( Fileshredder, 2008) t o the DoD 5220.22 M standard (DoD 5220.22 M, 2006). Experimental Design Data w as analyzed using experimental power for multiple regression techniques on 15 participants One tailed tests were used for the directional hypotheses below and two tailed tested were performed for all variabl es in a single correlation matrix to examine the data for any unexpected associations Hypotheses were as follows: Hypothesis 1: Internal locus of control will be associated with lower perceived stress, higher perceived health, lower cortisol levels and hi gher sIgA levels. Hypothesis 2: High coping ability will be associated with lower perceived stress, higher perceived health, lower cortisol levels and higher sIgA levels. Hypothesis 3: Synergistic effects between locus of control and coping will be represe nted by a high positive correlation coefficient between them. Equipment Questionnaires Duttweiler Internal Control Index was used to asses combined was administ ered to asses combined coping skills across seven categories

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Locus of Control, Coping, Stress and the Immune System 39 including r eactivity to stress, a bility to assess situation, s elf reliance, r esourcefulness, a daptability and flexibility, p roactive attitude, and a bility to relax. Perceived health was measured using the SF 36 v2 Health Survey (Ware, Kosinski, Bjorner, Turner Bowker, Gandek, & Maruish, 2007) a short form questionnaire extensively validated for use with adolescents and adults. Perceived stress was measured using the Perceived Stress Scale 10 ( PSS 10 ) (Cohen, Kamarck, & Mermelstein, 1983) All measures utilized Likert scales of the four, five or seven point variety. Saliva Collection Saliva collection was accomplished using the passive drool protocol recommended by Salimetrics in combination with the Saliva cryovial #5002.01. Participants were asked to think of their favorite food and drool through a 2 inch length of tubing into the cryovials. The time it took each participant to secrete 1ml of saliva was measured and a saliva flow rate was calcul ated for sIgA measurement. Samples were shipped overnight to a Salimetrics lab in Pennsylvania stored in an insulated container with dry ice to prevent decomposition of metabolites in the saliva. Cortisol and sIgA were both measured in duplicate for each s ample with the means averaged.

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Locus of Control, Coping, Stress and the Immune System 40 Result s Table 1 Cortisol Levels from Salivary Assay Sample ID result (ug/dL) 1 0.426 2 0.111 3 0.207 4 0.294 5 0.187 6 0.062 7 0.047 8 0.108 9 0.139 10 0.213 11 0.286 12 0.614 13 0.345 14 0.102 15 0.157 Ta ble 2 Secretory Immunoglobulin A Salivary Assay Results ID Time (min) Saliva Collected (ml) Flowrate (mL/min) Result 1 Result 2 Mean (ug/mL) Corrected SIgA mean (ug/min) 1 1.5 1 0.67 198.61 209.57 204.09 136.06 2 3.6 1 0.28 284.98 306.91 295.94 82.21 3 5.7 0.5 0.09 293.91 293.91 293.91 25.78 4 2.9 1 0.34 636.65 636.65 636.65 219.53 5 3.2 1 0.31 338.96 365.41 352.18 110.06 6 1.2 1 0.83 205.64 211.55 208.60 173.83 7 1.6 1 0.63 118.85 127.32 123.08 76.93 8 1.6 1 0.63 153.01 172.40 162.71 101.69 9 5.5 1 0.18 280.61 291.20 285.91 51.98 10 1.0 1 1.00 193.00 204.99 199.00 199.00 11 3.3 1 0.30 269.58 277.17 273.37 82.84 12 2.9 1 0.34 175.80 182.18 178.99 61.72 13 4.9 0.5 0.10 156.65 148.93 152.79 15.59 14 3.0 1 0.33 327.55 332.69 330.12 110.04 15 3.0 1 0.33 145.91 175.80 160.86 53.62 sec/60 vol (mL)/ min flowrate x mean

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Locus of Control, Coping, Stress and the Immune System 41 Table 3 Locus of Control 1 LoC sIgA Cortisol pstress Physical Mental Spearman's rho LoC Correlation Coefficient 1.000 .295 .050 .608 .236 .548 Sig. (1 tailed) .143 .430 .011 .198 .017 N 15 15 15 14 15 15 Table 4 Coping 1 Coping sIgA Cortisol pstress Physical Mental Spearman's rho Coping Correlation Coefficient 1.000 .253 .387 .551 .201 .228 Sig. (1 t ailed) .182 .077 .020 .237 .207 N 15 15 15 14 15 15 *. Correlation is significant at the 0.05 level (1 tailed). The results were obtained approximately two weeks after samples arrived at the Salimetrics testing facility. The samples arrived to goo d condition, still frozen in an insulate d container on a bed of dry ice. Values for the cortisol were averaged from two duplicate assays on the same sample, while sIgA was measure in singlet for cost effectiveness. sIgA values were adjusted for recorded s alivation report measures were coded and recorded by the experimenter according to their respective coding procedures. For coping, perceived health and perceived stress, h igher values indicated better coping skills, higher levels of perceived health and more perceived stress. Locus of control was measured on a scale of internal to external with higher values indicating a more external LoC.

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Locus of Control, Coping, Stress and the Immune System 42 Discussion As hypothesized, Inter nal locus of control was associated with lower perceived stress and higher perceived health, though only mental health was significant r(15) = .548, p = .017 This is exactly the opposite of the expected hypothesis and is still significant in a two tail ed test at r(15)= .548, p=.034 indicating that among those tested, individuals with more internal loci of control tend to have lower levels of perceived mental health. One possibility, given the data, is that s tudents at New College tend to have highly ex ternal loci of control leading to a largely homogenous experimental sample. In addition students are participating in a rigorous and stressful academic program which may cause a deterioration of perceived mental health in a measure based on self report. W hen these factors combine it is possible that the largely homogenous population which resides towards the external end of the LoC scale is producing a spuriously large correlation coefficient relative to the values towards the lower end of the LoC scale. I n a sample this size it is critical to examine the data graphically for any outliers.

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Locus of Control, Coping, Stress and the Immune System 43 Figure 1 Scatterplot of Locus of Control and Perceived Mental Health Alternatively there may be a number of factors confounding the results. Since the recruit ing for this experiment was conducted on a self selecting volunteer basis the experiment may have drawn participants that had lower perceived mental health in general. These participants would, due to the universally internal locus of control found in the sample, have been predisposed to participate in an experiment that allowed them to learn more about their mental health as it related to other factors. In contrast, there may have been a ceiling effect in the measurement of Locus of control which prevente d sufficient

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Locus of Control, Coping, Stress and the Immune System 44 stratification based on that variable, given the homogenous nature of the sample. Finally, the strong reversal of the experimental hypothesis may be due to a higher awareness of mental problems amongst the sample and a greater burden of respo nsibility for those problems amongst those with an internal locus of control. This is likely the true reason for the high negative correlation, as the perceived physical health measure evidences a moderate but not significant negative correlation r(15)= .2 36, p=.198 that parallels that of the perceived mental health measure. While this correlation may seem to only be representative of psychological measures it is important to recall that the specific measures of perceived mental health tap behaviors similar to those experienced by a sick individual including social withdrawal. The underpinnings of these psychological factors may indeed be the IL 1 and IL 2 cytokines associated with bottom up immune talkback and in some instances depression (Myint et al., 20 05) The strong association of external LoC with lower perceived stress r(14)= .608, p=.011 likely stems from several causes both physical and psychological. Again a ceiling effect in the locus of control measure presents itself as a possibility, but in this case the values are evenly distributed on the scatter plot and there are no outlier values.

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Locus of Control, Coping, Stress and the Immune System 45 Figure 2 Scatterplot of Locus of Control and Perceived Stress The negative correlation in this case strongly confirms the experimental hypothesis showin g that an internal locus of control is highly associated with lower perceived stress. As discussed in the literature above this is likely due to the fact that individuals with an internal locus of control are more likely to display dispositional optimism, making unstable, local attributions which cast unfavorable events as alterable by the individual. The association between coping and perceived stress falls along similar lines and of course has a similar and equally

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Locus of Control, Coping, Stress and the Immune System 46 strong coefficient of correlation r(14)= .551, p=0.020 meaning it accounts for 30% of the variance in the experiment Participants with strong coping skills had very low perceived stress likely due to a large inventory coping methods which can be effectively utilized by the individual in questio n. These learned skills minimize physiological reactivity to stressors by actively removing or minimizing the stressor before mobilization of long term stress response such as the HPA axis. Interestingly though both LoC and coping are strongly associated with perceived stress the hypothesized synergistic association between them failed to materialize, eliciting an extremely small correlation coefficient r(15)=.046, p=871. The small correlation between LoC and coping evinces very little overlap between the measures and shows them to be discrete influences on any given variable with little in the way of interaction. Perceived stress can be seen to be influenced by both, but in the sample a combination highly internal LoC and strong coping scores were not fo und to be more strongly associated with decreased perceived stress than either variable separately. Neurobiologically, perceived stress is known to be strongly linked to levels of Cortisol on a long term basis however the relationship between those two va riables in this study was relatively weak r(15)=.115, p=.697 though still positive as hypothesized. This along with the lack of strong association of Cortisol with any of the tested variables leads to some questions about the validity of the snapshot des ign of the study with regard to physiological metabolites. This relationship should have been the strongest association for that metabolite, given the significant amount of literature predicting bidirectional interaction between the

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Locus of Control, Coping, Stress and the Immune System 47 two variables. Lookin g at the associations at one brief point in time however, may not have adequately captured what has traditionally been observed as a longitudinal covariate relationship between Cortisol and stress. sIgA in contrast was somewhat positively correlated with locus of control, as expected, though not significant r(15)=.295, p=.143. The moderate association between sIgA and LoC is likely indicative of both a physiological process as hypothesized above as well as different reactions to health issues. There is a higher likelihood that individuals with a highly external LoC will be more concerned with their health related behaviors and take more opportunities to engage in positive ones, indirectly increasing their immunocompetence as measured by sIgA. Despite mod erate association in the positive direction as predicted, sIgA was not significant even in a 1 tailed test. This may be due to the small sample size, or the homogenous nature of the sample with regards to the LoC variable. Given the non significant relati onships found between LoC and the physiological variables, it is likely that a more longitudinal approach is needed in conjunction with a larger sample size to fully reveal the association between Cortisol, sIgA, LoC and stress. The Coping skills variable as mentioned above was highly associated with perceived stress, but the physiological linkages expected between Coping and stress were again smaller than expected and not quite significant. The association between coping and Cortisol was negative as predi cted and very close to significance r(15)= .387, p=.077. This demonstrates reduction of stress in individuals that have access to a large inventory of coping strategies and the

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Locus of Control, Coping, Stress and the Immune System 48 self efficacy to utilize them. Additionally, there was a moderate positive ass ociation r(15)=.253, p=.182 between coping and levels of sIgA. This follows the predicted trend and though not significant, indicates that given a more in depth study, coping skills may be a useful indicator of possible downstream effect of stress on the i mmune system. There were no significant or moderate associations between coping and mental or physical health, but this is not surprising given the multi causal nature of the direct relationships between them in the literature. In fact, it is unlikely that they would be associated in the absence of pre existing health issues. Thus, though hampered by the homogeneity and size of the available sample, most relationships found in the literature were confirmed. Additionally, though not significant in this sam ple, the research hypotheses regarding LoC vs sIgA and Coping vs sIgA vs Cortisol were shown to be strong enough to merit further study. Conclusion It is important to reiterate at this point that while there are important effects on immune function and ot her physiological variables due to stress, stress is not generally the primary factor leading to health issues. This is particularly true in related stress where 85% of poor health outcomes (CHD, Stroke etc) were accounted for by biomedical factors rather than psychological factors. It is clear from the data in this pilot study that there are relationships strong and weak between physiological variables that respond to stress and p ersonality variables shown to

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Locus of Control, Coping, Stress and the Immune System 49 affect attributional processes in stress. These associations become important primarily when other factors predispose an individual towards illness and as such would not be expected to be highly correlated with health in a rel atively homogenous, healthy young sample. The observed relationships provide fertile ground for further research. The significant correlations found for LoC and Coping, while interesting are merely confirmatory of previous literature. They are necessary to link stress to stable, measurable, personality traits. The truly enlightening results however, involve the physiological measures. The correlations between LoC and sIgA, Coping and sIgA and Coping and Cortisol, were not significant, but are noticeable and act in the pr edicted direction. Internal LoC and high coping ability both correlate with lower cortisol levels and higher levels of sIgA lending credence to the theory that that LoC and Coping can be useful predictors of physiological stress and immun e competence. If replicable these results would present a model by which LoC and Coping could be directly linked to immune competency via the psychological appraisal of stress and the physiological response thereto. In a larger sample, particularly a more heterogeneous one with regard to health and LoC variables, the associations between physiological variables and the measured personality traits would likely become significant. Given the nature of the interaction between health, its relationship to physio logical measures of stress, and the exacerbation of underlying conditions by physiological correlates of psychological phenomena, it becomes clear that a sample with more varied levels of health would be beneficial. If these linkages were more fully explor ed

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Locus of Control, Coping, Stress and the Immune System 50 and found to hold true they could open up new avenues for treatment of illness and a more useful understanding of stress at an individual level. The concept of augmenting health via psychological means is not a new one and indeed was implemented long b efore the physiological relationships between psychological factors and neuroimmunological processes were conceived, much less explored. A number of recent studies have explored the effects of psychological intervention to address general health related is sues such as compliance with medical professionals and the likelihood an individual will seek assistance. More recently it is being applied to more specific targets such as reducing post operative risk of infection as it relates to allostatic load (McEwen, 1999) Psychology has, at its core, been manipulating neuroimmunological variables since its inception, but its effects are not typically measurable in a discrete physical manner. Though newer research into neurobiology is furthering the understanding of psychological factors there remains a gap between the physically measurable understanding of neuroscience and the functionally measurable effect of psychological traits and treatments. The results above show that that gap is narrowing, particularly with regard to stress, and reinforce the need for a unified stress measurement scale validated by a strong understanding of the physiological underpinnings of psychological stress.

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Locus of Control, Coping, Stress and the Immune System 51 Appendix A CONSENT FORM Effect of Commonly Studied Personality Variables on Stress and Immune Response: An Analysis Locus of Control and Coping Strategies You are invited to be in a research study of locus of control and coping strategies as they affect physiological and psychological variables You were selected as a possible par ticipant because you are over 18 and have no health problems which could complicate salivary analyte assays We ask that you read this form and ask any questions you may have before agreeing to be in the study. This study is being conducted by: Ben jamin S tork o New College of Florida o 5800 Bay Shore Drive o Sarasota, FL 34234 Background Information Perception of the world around us is vital to the human experience. Humans are uniquely complex in their view of the world due to the number of seemingly intangib le variables that color our perception of each and every experience. One of the most broadly descriptive variables that affect human perception is how much control an individual believes they have in their life, often referred to as locus of control (LoC) LoC combined when analyzed in combination with coping effectiveness has been shown to present a compelling picture of how humans perceive life events. Given these tenets it should be no surprise that the way humans relate to the world has long been a f ield of vigorous study. The delineation between anatomical, physiological and psychological factors affecting how we perceive life events is not often clear, but in many ways the attempt to separate these factors is a falsehood that reduces clarity even f urther. These seemingly disparate factors have only recently become so and in fact were integrated in early science. What was integrated by lack of understanding has now come full circle to be reintegrated as the understanding of psychoneuroimmunological linkages is more fully explored. Indeed physiological factors have come to the fore in recent research as means by which to quantify

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Locus of Control, Coping, Stress and the Immune System 52 otherwise intangible concepts such as stress. First among these physiological variables is cortisol, a corticosteroid wh ose levels are associated with both the chronic and acute affects of stress. A second measure, secretory Immunoglobulin A is used to measure immune competence. This study, unlike many before it will attempt to directly quantify the effects of LoC and copi ng strategies on the body without the incontinently intangible intermediary known as stress. If you agree to be in this study, we would ask you to do the following things: Participate in saliva collection Participate in four short self report surveys Re ceive and exciting toy for your participation Risks and Benefits of being in the Study The study has several risks: First, minimal risk of emotional discomfort from filling out a survey regarding stress levels The likelihood of significant impact from this factor is very small. The benefits to participation are: The direct relationship of locus of control and coping strategies to physiological and psychological variables will be furthur elucidated. This would provide possible avenues for research into interventions for those at risk according to these variables. Compensation: You will receive payment: A small toy from the Oriental Trading Company Confidentiality: The records of this study will be kept private. In any sort of report we might publish, we will not include any information that will make it possible to identify a subject. Research records will be stored securely and only researchers will have access to the records. Voluntary Nature of the Study: Participation in this study is voluntary. You r decision whether or not to participate will not affect your current or future relations with New College of Florida, or the

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Locus of Control, Coping, Stress and the Immune System 53 experimenters. If you decide to participate, you are free to not answer any question or withdraw at any time without affecting tho se relationships. Contacts and Questions: The researcher conducting this study is: Benjamin Stork. You may ask any questions you have now. If you have questions later, you are encouraged to contact him at Y4110 (830)643 4193, Benjamin.stork@ncf.edu or his academic advisor Dr. Beulig at HNS 117A (941)487 4374. beulig@ncf.edu Resources for Stress Management : Counseling & Wellness Center New College of Florida CWC 120 5800 Bay Shore Road Sarasota, FL 34243 (941) 487 4254 Hours: 8am 5pm M F Bayside Center for Behavioral Health 1650 S. Osprey Avenue Sarasota, FL, FL 34239 941 917 7760 Hours : 24/7 The Listening Ear Crisis Intervention Center 24 hour Crisis Line (517) 337 1717 I have read the above information. I have asked questions and have received answers. I consent to participate in the study. Signature:________________________________________ Dat e: ___________ Signature of Investigator:_____________ _______________Date: __________

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Locus of Control, Coping, Str ess and the Human Immune Response 54 Appendix B Participate in an enlightening, exciting, ephemeral senior thesis project! LEARN! Where your locus of control resides What coping mechanisms you favo r How this affects many thrilling physiological factors in your OWN BODY! Receive! A spiffy toy! Brainbusting amounts of knowledge Self awareness* Contact! Benjamin Stork for more information benjamin.stor k@ncf.edu *Level of self awareness attained may vary but you will at least be aware that your self is participating in an experiment

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Locus of Control, Coping, Str ess and the Human Immune Response 55 Appendix C Overall Correlation Matrix sIgA Cortisol LoC pstress Coping Physical Mental Spearman's rho sIgA Correlati on Coefficient 1.000 .039 .295 .236 .253 .132 .379 Sig. (2 tailed) .889 .285 .417 .364 .639 .164 N 15 15 15 14 15 15 15 Cortisol Correlation Coefficient .039 1.000 .050 .115 .387 .168 .136 Sig. (2 tailed) .889 .859 .697 .154 .550 .630 N 15 15 15 14 15 15 15 LoC Correlation Coefficient .295 .050 1.000 .608 .046 .236 .548 Sig. (2 tailed) .285 .859 .021 .871 .396 .034 N 15 15 15 14 15 15 15 pstress Correlation Coefficient .236 .115 .608 1.000 .551 .143 .703 ** S ig. (2 tailed) .417 .697 .021 .041 .625 .005 N 14 14 14 14 14 14 14 Coping Correlation Coefficient .253 .387 .046 .551 1.000 .201 .228 Sig. (2 tailed) .364 .154 .871 .041 .473 .415 N 15 15 15 14 15 15 15 Physical Correlation Coefficien t .132 .168 .236 .143 .201 1.000 .179 Sig. (2 tailed) .639 .550 .396 .625 .473 .524 N 15 15 15 14 15 15 15 Mental Correlation Coefficient .379 .136 .548 .703 ** .228 .179 1.000 Sig. (2 tailed) .164 .630 .034 .005 .415 .524 N 15 15 15 14 15 15 15 *. Correlation is significant at the 0.05 level (2 tailed). **. Correlation is significant at the 0.01 level (2 tailed).

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