The term stress can be confusing since it can refer to a stimulus, response, and a transaction. The conceptualization of the stress response as nonspecific is misleading since clients may have unique stress triggers (a specific ring tone) and their patterns of psychophysiological change can be very specific (colitis). While early theories of stress emphasized the role of stimuli, more recent theories focus on our cognitive appraisal of events and coping resources. The biopsychosocial model has replaced the aging biomedical model due to its greater comprehensiveness and support for interdisciplinary treatment of disorders.
 


This unit covers Stress and the biopsychosocial model of illness (II-A), Stressful life events and risk of illness (II-B), Psychophysiological reactions to stressful events (II-C), and Psychosocial mediators of stress (II-D). 
 
Students completing this unit will be able to discuss:

  1. Stress and the biopsychosocial model of illness
  2. Stressful life events and risk of illness
    A. Assessing stressful life events
    B. Traumatic stress and posttraumatic stress disorder
  3. Psychophysiological reactions to stressful events
    A. Negative affect (e.g., anxiety, anger, hopelessness, depression)
    B. Acute stress: Cannon’s fight or flight response
    C. Chronic stress: Selye’s general adaptation syndrome
    D. Immune system disruption
  4. Psychosocial mediators of stress
    A. Cognitive appraisals of stress and coping resources
    B. Personality dispositions (e.g. optimism, pessimism, self-efficacy)
    C. Social support





Hans Selye (1956) referred to stress as a response to stimuli called stressors. He conceptualized this response as nonspecific since many stimuli can produce the same physiological changes.



Selye (1956) theorized that both negative and positive stimuli can produce a stress response. He termed stress due to negative stimuli, distress, and that due to positive stimuli, eustress.



Each person responds to stressors in a unique way. This is called response stereotypy. A sympathetic responder may react with sweaty hands, rapid heart rate, and elevated blood pressure. The stress response is not always “fight or flight.” A parasympathetic responder may increase digestive activity, constrict the alveoli of the lungs, and faint from low blood pressure.
 


Engel's (1977, 1980) biopsychosocial model proposes that the complex interplay of psychological, biological, and sociological factors results in health or illness. In this model, stress is a psychological risk factor that affects and is influenced by an individual's biology and sociology. The biopsychosocial model challenges the biomedical model, that illness is primarily due to biological abnormalities, which has influenced medical practice since the 1700s (Taylor, 2006). A clinician who adopts the biopsychosocial model assumes that health depends on all three sets of factors and that these factors must be assessed and addressed using an interdisciplinary approach when treating illness (Schwartz, 1982). 



                                                     


Evidence supporting the biopsychosocial model include the increased rates of psychological and medical disorders in divorced and bereaved persons (Schneider, 1984).

                                                                

Allostasis means matching type (sympathetic or parasympathetic) and intensity of physiological activation to situational demands (Brannon & Feist, 2004). The allostatic load model (McEwen & Seeman, 1999) proposes that when stressors are acute or repeatedly occur, biological responses to stress (e.g., cortisol secretion or elevated glutamate transmission) can have an aversive impact on the body. Over time, the stress response, itself, may overwhelm body systems. Researchers have linked high allostatic load to illness in children and the elderly (Johnston-Brooks et al., 1998; Seeman et al., 1997).



The stress-diathesis model explains that stressors interact with our inherited or acquired biological vulnerabilities, diathesis, to produce medical and psychological symptoms. From this perspective, disease results when an individual is predisposed to a disease and experiences stress. Life event scales like the SRRS and USQ may achieve low predictive validity because they only and incompletely assess stress; they do not evaluate vulnerability to illness (Marsland et al., 2001).



Birnbaum and colleagues (2004) reported that uncontrollable stressful situations activate the enzyme protein kinase C (PKC), interfering with prefrontal cortical functions like working memory. Elevated PKC levels may result in symptoms of distractibility, impulsiveness, and poor judgment seen in bipolar disorder and schizophrenia. Initial psychotic episodes often follow stressors like leaving home for college or the military. Very low levels of lead exposure can elevate PKC levels in children, possibly impairing their regulation of behavior and producing distractibility and impulsivity.



Epel and colleagues (2004) studied 58 healthy women who provided care for either healthy or chronically-ill children. The researchers administered a brief questionnaire that assessed chronic stress during the previous month and obtained a blood sample to measure telomere (DNA and protein that cover the ends of chromosomes) length and levels of telomerase (an enzyme that adds DNA to telomeres). With repeated cell division, telomere DNA is lost, the telomere shortens, and eventually cell division stops. When cells age, telomerase activity declines and the telomere shortens.

The researchers found that the mothers of chronically-ill children reported higher chronic stress levels than mothers of healthy children. More years caring for chronically-ill children were correlated with shorter telomeres and lower telomerase levels. Perceived levels of chronic stress—and not a child's actual health status—predicted telomere length. The researchers calculated that the cells of high-stress mothers had aged 9 to 17 more years than those of the low-stress mothers.

 



Holmes and Rahe (1967) measured major positive and negative life changes using their Social Readjustment Rating Scale (SRRS). The scale lists 43 events, each assigned a different Life Change Unit (LCU) value. They arranged these events in descending order from death of a spouse (100 LCUs) to minor violations of the law (11 LCUs). Individuals select the events they have experienced within the last 6 to 24 months. Researchers calculate a stress score by summing the LCU value of the checked events. Studies that combine prospective (subjects report current events) and retrospective methods (researchers examine subsequent health records) have reported increased illness and accidents following increased stressful events (Johnson, 1986; Rahe & Arthur, 1978). However, the correlation between SRRS scores and illness is around + 0.30 (Dohrenwend & Dohrenwend, 1984), which means that the SRRS accounts for only 9% of the variance in illness.

The SRRS's popularity has received severe criticism and its popularity has declined. Critics have argued that its positive events can actually reduce the risk of illness (Ray, Jefferies, & Weir, 1995), the SRRS assumes that an event impacts all people equally, the wording of some items is vague (e.g., "change in responsibilities at work"), pessimism can distort recollections of life events (Brett et al., 1990), and the scale does not control for whether an event has been resolved (Turner & Avison, 1992) or events controllability or probability (Gump & Matthews, 2000).

The Undergraduate Stress Questionnaire (USQ) developed by Crandall and colleagues (1992) instructs students to select events—mostly hassles—they have experienced during the past two weeks. Higher USQ scores are associated with increased use of health services.

The Perceived Stress Scale (PSS) developed by Cohen and colleagues (1983) measures perceived hassles, major life changes, and shifts in coping resources during the previous month using a 14-item scale. PSS items assess the degree to which respondents rate their lives as unpredictable, uncontrollable, and overloaded (p. 387). The PSS achieves good reliability and validity (Brannon & Feist, 2004). PSS scores predict cortisol levels (Harrell et al., 1996), fatigue, headache, and sore throat (Lacey et al., 2000), and immune changes (Maes et al., 1997).



A hassle is a minor stressful event like waiting in line. An uplift is a minor positive event like receiving an unexpected call from a friend. Kanner and colleagues (1981) developed a 117-item Hassles Scale and 138-item Uplifts Scale to measure negative and positive daily experiences. Respondents selected the hassles and uplifts they experienced during the previous month. Next, they rated the degree to which they experienced each selected item on a 3-point scale to assess their perception of each stressor. They found a moderate correlation between hassles and major life changes. Lazarus (1984) reported that the Hassles Scale better predicted psychological health than major life changes.

DeLongis, Folkman, and Lazarus (1988) replaced the Hassles and Uplifts Scales with a 53-item revised Hassles and Uplifts Scale. Respondents selected the items they experienced that day and rated each item using a 4-point scale (none to a great deal). The revised Hassles Scale better predicted headache frequency and intensity (Fernandez & Sheffield, 1996) and inflammatory bowel disease frequency (Searle & Bennett, 2001) than the SRRS. Consistent with Lazarus's emphasis on appraisal of events, the perceived intensity of hassles better predicted headache symptoms than the number of hassles.

The interaction between hassles and chronic stress is complex. Hassles may increase the psychological distress produced by chronic stress (Serido, Almeida, & Wethington, 2004). Conversely, chronic stress may reduce the effects of hassles by placing them in perspective (McGonagle & Kessler, 1990).
 


Traumatic stress is produced by an extremely intense stressor that disrupts coping and endangers ourselves or others. Posttraumatic stress disorder (PTSD) is a severe and long-lasting anxiety disorder that often develops within three months of a traumatic event. The exposure can also be second-hand, such as witnessing domestic violence or learning about a family tragedy (Crider, 2004; Lamprecht & Sack, 2002). The American Psychiatric Association (2000) estimates the lifetime prevalence of PTSD in the United States at about 8 percent.





While the earliest model of PTSD focused on trauma during combat, subsequent research has shown that crime, domestic violence, natural disasters, sexual assault, and terrorism can precipitate PTSD symptoms. Since women are more likely than men to experience these stressful events, it should not be surprising that they are more often diagnosed with this disorder (Stein et al., 2000). Children and adolescent victims and witnesses of violence also share an elevated risk of PTSD (Silva et al., 2000).

PTSD can permanently damage the systems that regulate our stress response, particularly the amygdala and hypothalamic-pituitary-adrenal (HPA) axis. Researchers have documented increased fluctuation in cortisol levels and persistent elevations in epinephrine, norepinephrine, testosterone, and thyroxin (Taylor, 2006).

PTSD may promote medical illness through persistent immunosuppression (Kawamura et al., 2001). Military veterans diagnosed with PTSD have a greater risk of developing serious diseases following discharge than veterans without PTSD (Deykin et al., 2001). PTSD may also exacerbate pre-existing health problems. PTSD resulting from the September 11, 2001 World Trade Center attacks may have helped worsen asthmatic symptoms in New York residents (Fagan et al., 2003).



Stressors can trigger complex adjustments that include negative affective states (anxiety) and corresponding psychophysiological changes (decreased heart rate variability). Barrett and Russell's (1998) structural model represents each affective state within a circumplex based on its degrees of affective valence (unpleasant to pleasant) and affective intensity (activation to deactivation). This allows an affective state to fall inside or along the surface of this circular structure.

Negative states (sad) are located in the left hemisphere and positive states (contented) are located in the right hemisphere. Activated states (tense) are placed in the top hemisphere and deactivated states (fatigued) are placed in the bottom hemisphere. While adjacent affective states (stressed and nervous) most resemble each other, those 180o apart (stressed and relaxed) are opposites. After clinicians identify their clients' position within the circumplex, they may intervene to shift them to a more appropriate affective state, like relaxed instead of nervous.




                                                                   


 Researchers have reported psychophysiological correlates of the affective valence and activation dimensions. Surface EMG (SEMG) and EEG can help assess affective valence. SEMG measurements of the zygomatic (smiling) and corrugator (frowning) muscles are correlated with positive and negative affect (Lang et al., 1993). Higher left/right prefrontal cortex activation ratios are correlated with positive affect, while reverse ratios are correlated with negative affect (Sutton & Davidson, 1997). Sympathetic nervous system modalities like electrodermal activity are associated with affective intensity (Crider, 2004; Lang et al., 1993).



Negative affectivity is a predisposition toward distress and dissatisfaction. Individuals who are rated high on this trait negatively perceive themselves, others, and the environment, and have a pessimistic perspective. They rate more events as stressful and report more intense stress, and complain more frequently about health problems and report more severe symptoms when they are actually sick than those with lower negative affectivity (Cohen et al., 1995; Gunthert et al., 1999). Negative affectivity may increase vulnerability to stressors and health conditions like anxiety and depressive disorders they exacerbate (Brannon & Feist, 2004).



A Framingham study report by Markovitz et al. (1993) showed that men with elevated anxiety had twice the risk of middle age hypertension as men with lower anxiety. This increased risk was not found for women. A prospective study by Kawachi et al. (1994) revealed that men diagnosed with phobic anxiety had a three times greater risk of sudden cardiac death. Albert et al. (2005) found that women diagnosed with phobic anxiety had a 59% greater risk of sudden cardiac death and 31% greater risk of fatal coronary heart disease compared with women who scored low. These increased risks were associated with risk factors such as diabetes, hypertension, and high cholesterol.



Pratt et al. (1996) reported that depressed individuals had a four times greater risk of heart attack in the next 14 years than nondepressed individuals. Frasure-Smith et al. (1995) found that depressed heart attack patients had a four times greater risk of another heart attack in the next 18 months than nondepressed heart attack patients. Carney et al. (2005) discovered that depressed heart attack patients were almost three times more likely to die during a 30-month period than nondepressed heart patients. Decreased heart rate variability accounted for a significant share of the increased risk of death.

Jonas and Mussolino (2000) found in a 16-year longitudinal study that participants diagnosed with depression had a 70% greater risk of stroke that was mediated by ethnicity. Stroke risk was higher for depressed European American men than women and for depressed African Americans than European Americans. Everson et al. (1998) reported that depressed individuals had a greater risk of death from stroke than nondepressed participants.



Friedman and Rosenman (1974) proposed the Type A-B continuum of risk for coronary artery disease. They described extreme Type A’s as competitive, concerned with numbers and acquisition, hostile, and time-pressured. In contrast, the Type B's are less motivated and do not usually exhibit Type A behaviors. Their study of 3,000 men over 8.5 years showed that Type A behavior doubled the risk of heart attack. The National Heart Lung and Blood Institute (1981) concluded that Type A behavior is an independent risk for heart disease.

Despite early hopes that the global Type A behavior pattern could independently predict heart disease, current research has not consistently supported this association (Brannon & Feist, 2004).



Williams (1989) reported that cynical hostility, where individuals mistrust humanity and those they interact with, threatens cardiovascular health. Siegler, Peterson, Barefoot, and Williams (1992) discovered that hostility is not an independent risk factor for heart disease, but is rather associated with alcohol consumption, obesity, and smoking, which affect the development of heart disease. When researchers control these three factors, the association between hostility and heart disease vanishes (Everson et al., 1997).

The failure of cynical hostility to independently predict heart disease has focused attention on a component of hostility called expressed anger (Brannon & Feist, 2004).



Hostility is a negative attitude towards individuals—not an emotion—and may persist for a long time. Taylor (2006) proposed that cardiovascular reactivity and hostility in conflict situations might promote heart disease through changes in blood vessels and catecholamine levels, sympathetic nervous system release of lipids into circulating blood, and blood platelet activation.

Anger is a negative emotion that involves physiological arousal and persists for a brief period. Siegman, Dembroski, and Ringel (1987) proposed that the expression of anger—and not our experience of it—could result in heart disease. Examples of expressed anger include raising your voice during arguments and temper tantrums (Brannon & Feist, 2004).

Jain, Burg, and Soufer (1995) monitored patients using an electronic stethoscope and observed declines in the heart's ejection fraction (the ratio of blood pumped by the left ventricle during a contraction compared to its total filling volume) when they were angry. Bhat and Bhat (1999) demonstrated that an intervention to manage anger using biofeedback significantly increased their patients' ejection fraction.

Expressed anger may contribute to heart disease by increasing cardiovascular reactivity (CVR), which is often revealed as increased blood pressure and heart rate in response to social stressors like provocation.

Dujovne and Houston (1991) linked expressed hostility with increased total cholesterol and low-density lipoprotein (LDL) in men and women. Goldman (1996) reported that individuals classified with high anger had a 2.5 times greater chance of re-clogging arteries after angioplasty. Siegman, Dembroski, and Crump (1992) reported that training to slow speech rate and lower speech volume reduced CVR.

Researchers have shown that provocation can increase cardiovascular reactivity.

Siegman, Anderson, Herbst, Boyle, and Wilkinson (1992) observed increased heart rate and blood pressure (diastolic and systolic) after provoking male undergraduates. The subjects reported experiencing considerable anger following their provocation.

Fredrickson et al. (2000) asked adult men and women to reexperience earlier anger experiences. Participants who were more hostile produced larger and longer-duration blood pressure increases than less hostile individuals. Also, African Americans showed greater CVR than European Americans.

Bishop and Robinson (2000) studied Chinese and Indian men in Singapore, who performed a difficult task either with or without harassment. The harassed participants showed greater CVR than those who were not provoked.

Smith and Brown (1991) found that women showed less CVR than men when provoked. While husbands increased their heart rate and systolic blood pressure while trying to control their wives, the wives did not experience these changes when trying to control their husbands. The wives' systolic blood pressure only increased when their husbands expressed cynical hostility.



Diamond (1982) hypothesized an anger-in dimension, which is the tendency to withhold the expression of anger, even when anger is warranted. Dembroski and colleagues (Dembroski et al., 1985; MacDougall et al., 1985) reported that anger suppression can contribute to heart disease. Siegman (1994) recommended that patients develop awareness their anger, but express it using a quiet, slow voice.
 


Cannon's fight-or-flight response focuses on sympathetic nervous system responses to an acute stressor and describes the sympathetic-adrenomedullary (SAM) pathway which releases the hormones epinephrine and norepinephrine. Selye's General Adaptation Syndrome describes our prolonged response to a chronic stressor across three stages, describes the hypothalamic-pituitary-adrenal (HPA) axis which releases the hormones CRH, ACTH, and cortisol, and explains how chronic stress can produce disease and death.




 


Cannon (1932) described the fight-or-flight response, in which an individual confronts or flees a stressor. During an acute stress response, which corresponds to the end of Selye's alarm stage, we activate the sympathetic nervous system (SNS), increasing respiration, cardiac output, blood flow to skeletal muscles, and metabolism, while decreasing digestion and the reproductive system activity. The SNS, in turn, activates the hard-wired sympathetic-adrenomedullary (SAM) pathway, resulting in the release of the hormones epinephrine and norepinephrine by the adrenal medulla (inner adrenal gland). The adrenal medulla releases epinephrine and  norepinephrine in about a 4:1 ratio (Fox, 2006).

The adrenal medulla, is the red inner region of the adrenal glands, which are located at the top of each kidney. This image depicts the left adrenal gland from an anterior view.







Epinephrine and norepinephrine, which are both catecholamines, mobilize blood glucose and fatty acids to provide energy for skeletal muscle contraction, increase blood flow to the muscles by increasing cardiac output and blood pressure, dilate coronary blood vessels, increase respiratory rate, increase metabolic rate, and heighten alertness. Epinephrine levels are higher when we are fearful and norepinephrine levels are higher when we are angry (Ward et al., 1983).

SAM activation is adaptive when its intensity and duration enable us to cope with an external threat. Low SAM activation facilitates athletic and cognitive performance, while intense SAM activation allows us to overcome physical threats. However, intense SAM activation is maladaptive in situations like panic attacks or anticipatory anxiety, where there is neither an external threat nor active coping. 

Intense SAM activation can threaten safety and produce medical complaints. Anger can constrict coronary arteries and reduce cardiac output in cardiac patients (Committee on Health and Behavior, 2001) and is a risk factor for both heart attacks and sudden cardiac death (Williams et al., 2000). Anxiety and acute grief, which can also produce intense SAM activation, are risk factors for sudden cardiac death (Engel, 1971; Kawachi et al., 1994). SAM activation also underlies common symptoms of chest pain, dizziness, and shortness of breath that can be confused with coronary insufficiency (Crider, 2004).



Taylor and colleagues (2000) theorize that a tend-and-befriend response is an alternative reaction to stressors. They believe that tending, nurturing behavior, and befriending, seeking and providing social support, may better characterize women. The tend-and-befriend response may protect their safety and the lives of their offspring. This response may be mediated by an interaction between the hormones oxytocin and estrogen, and endogenous opioids.
 




The General Adaptation Syndrome (GAS) was Selye’s (1956) three-stage model of chronic autonomic and endocrine system responses to stressors. Selye argued that diverse stressors produce a three-stage response (alarm, resistance, and exhaustion stages) in all subjects. In this model, a cold stressor is interchangeable with a shock stressor because they both produce the same autonomic and endocrine responses. Where Cannon showed that acute stress can change the functions of our internal organs, Selye mainly demonstrated using animal models that chronic stress can change their structure (Crider, 2004).

Alarm is the first stage of Selye’s General Adaptation Syndrome and consists of shock and countershock phases. The shock phase includes reduced body stress resistance and increased autonomic arousal and hormone release (ACTH, cortisol, epinephrine, and norepinephrine) that comprise the “fight-or-flight” response. In the countershock phase, resistance increases due to local defenses.

Resistance is the second stage of Selye’s General Adaptation Syndrome. Local defenses have made the generalized stress response unnecessary. Both cortisol output and stress symptoms, like adrenal gland enlargement, decline. While the person appears to be normal, adaptation to the stressor places mounting demands on the body which can subsequently lead to diseases of adaptation like hypertension as adaptation energy is depleted. Local defenses will break down if stressors persist.

Exhaustion is the third stage of Selye’s General Adaptation Syndrome. Increased endocrine activity depletes body resources and raises cortisol levels resulting in suppressed immunity and stress syndrome symptoms. Selye believed that the abnormally reduced level of parasympathetic activity, which we require for homeostatic balance, cripples immunity and can result in bronchial asthma, cardiovascular disease, depression, hypertension, hyperthyroidism, peptic ulcer, and ulcerative colitis. Eventually, the individual may die (Feist & Brannon, 2004).



 

                                                  


While Selye made a landmark contribution to our understanding of the role of chronic stress and glucocorticoid-mediated damage in disease, critics have challenged his characterization of the stress response as nonspecific and his conceptualization of stressors. Since most of Selye's research subjects were nonhuman animals, this may have caused him to largely overlook the role of human emotion and cognitive appraisal in the chronic stress response. Mason (1971) argued that the nonspecificity (consistent physiological changes) of our response to diverse stressors was due to the common emotional states they elicit.

While Selye's model allowed any stimulus—regardless of its valence or intensity—to function as a stressor, he failed to explain why some stimuli trigger a stress response and others do not. Once again, his focus on nonhuman animals may have caused him to exclude cognitive factors like appraisal that make stimuli stressful.



The hypothalamic-pituitary-adrenal (HPA) axis releases the hormones CRH, ACTH (corticotropin), and cortisol. This cascade starts with signals from the amygdala to the hypothalamus and ultimately targets the adrenal glands, which are located at the top of each kidney.

The adrenal cortex, which is the tan outer region of the adrenal gland, produces the hormone cortisol.








This pathway is regulated by negative feedback as rising cortisol levels inhibit hormone secretion by the hypothalamus and anterior pituitary.




                                   
 



In response to stressful stimuli, the central nucleus of the amygdala activates the paraventricular nucleus (PVN) of the hypothalamus, resulting in increased CRH release to the pituitary gland.

Chronic, elevated CRH levels in the bloodstream may enhance learning classically-conditioned fear responses, heighten arousal and attention, which increase readiness to respond to a stressor, increase the startle response, and reduce appetite and body weight, sexual behavior, and growth.



When CRH binds to the pituitary gland, it releases corticotropin (ACTH). ACTH triggers cortisol release by the adrenal cortex (outer part) and helps resist infection.



Glucocorticoids like cortisol help convert fat and protein to glucose and reduce inflammation. Chronic, elevated cortisol levels in the bloodstream adversely affect many organs, including the brain. Patients may experience hyperglycemia (elevated blood sugar), hyperinsulinemia (elevated insulin levels), increased gastric acid secretion and ulcer, and impaired immune function.

Cortisol release can affect gene transcription, thus producing long-term as well as immediate effects on the body, and setting the stage for a number of physical and psychological disorders (panic, PTSD, and somatization).

Cortisol binding to the amygdala increases CRH, ACTH, and cortisol release, amplifies the fear response, increases our ability to store implicit memories about stressful stimuli, and increases the amygdala’s ability to suppress the prefrontal cortex’s checks on emotional behavior (emotional hijacking).

Cortisol binding to the hippocampal formation disrupts the medial temporal lobe memory system’s creation of explicit (conscious) memories, disrupts the hippocampus’s check on the PVN of the hypothalamus, and harms and kills cells in the hippocampus.

Two pathways from the raphe system terminate in the hippocampus: an anxiogenic, or anxiety-producing, pathway and an anxiolytic, or anxiety-reducing, pathway. Elevated cortisol levels suppress the anxiolytic pathway and facilitate the anxiogenic pathway, increasing anxiety in a chronically stressed individual.

Cortisol binding to the dorsolateral and ventromedial prefrontal cortex disrupts executive functions like attention and decisions, increases fear and anxiety, and harms and kills neurons.



 



Four brain structures most important to the stress response are the amygdala, hypothalamus, hippocampus, and prefrontal cortex.

The amygdala is part of the limbic system and participates in evaluating whether stimuli are threatening, establishing unconscious emotional memories, learning conditioned emotional responses, and producing anxiety and fear responses.




      



The hypothalamus lies beneath the thalamus in the forebrain and helps the body maintain a dynamic homeostatic balance through its control of the autonomic nervous system, endocrine system, survival behaviors (four F’s), and interconnections with the immune system.




      


Much of the information about stressors is relayed to the paraventricular nucleus, a nucleus in the hypothalamus that organizes behavior, including eating, to respond to changes in internal body states. The paraventricular nucleus receives input from the limbic system and cerebral cortex (via the bed nucleus of the stria terminalis), other parts of the hypothalamus, and brain stem structures (nucleus of the solitary tract, tegmentum and reticular formation, periaqueductal gray, locus coeruleus, and raphe system).




      


When the paraventricular nucleus is excited, it releases a number of chemical substances, including corticotropin releasing factor (CRH), oxytocin, arginine-vasopressin, thyrotropin-releasing hormone, growth hormone-releasing hormone, somatostatin, dopamine, enkephalin, cholecystokinin, and angiotensin.

This large variety of hormones allows the individual to respond to a wide range of stressors. Since stressful events are often comprised of many stressors being presented at once, these chemical substances allow the individual to respond completely and appropriately to a stressful situation.

The hippocampus is part of the medial temporal lobe memory system and helps form declarative memories, allows us to navigate within our environment, and prevents excessive release of corticotropin releasing factor (CRH) by the hypothalamus.




       


The prefrontal cortex is responsible for the brain’s executive functions, including planning, guiding decisions using emotional intelligence, working memory, allocation of attention, emotional experience, and inhibition of emotional behavior triggered by the amygdala.




      



Below is a BioTrace+ / NeXus-10 screen that provides skin conductance biofeedback to help clients learn to relax. The petals of the water lily unfold as skin conductance declines.







The human body utilizes both nonspecific and specific immune mechanisms to protect itself against invading organisms, damaged cells, and cancer. The main nonspecific mechanisms include anatomical barriers (skin and mucous membranes), phagocytosis (ingestion of microorganisms) by lymphocytes (macrophages and natural killer cells), release of antimicrobial agents (hydrochloric acid, interferons, and lysozyme), and local inflammatory responses that confine microbes and allow white blood cells to attack them.




                                                   


We develop specific immunity after birth through exposure to microorganisms and vaccinations, and it employs an antigen-antibody reaction to protect us against specific microorganisms and their toxins. Antigens are foreign proteins that stimulate antibody production. Antibodies are cellular proteins that combine with antigens to neutralize them.





        


Humoral and cell-mediated immunity are two types of specific immune responses. In humoral immunity,
B lymphocytes rapidly produce antibodies that counter bacteria into the blood, neutralize their toxins, and prevent reinfection by viruses. Activated B cells differentiate into plasma cells, which secrete antibodies (immunoglobulins), and memory B cells, which are transformed into antigen-specific plasma cells when they reencounter the original antigen. Humoral immunity is most effective in countering bacterial infection and preventing new viral infections.

Cell-mediated immunity provides a slower, cellular response that utilizes cytotoxic and helper T cells from T lymphocytes provided by the thymus gland. Cytotoxic T (TC) cells release toxins to destroy specific virally-infected cells. Helper T (TH) cells release cytokines like interleukin-2 to aid the action of TC and B cells, and macrophages. TH cell cytokines can also suppress immune responses. Cell-mediated immunity is most effective in controlling cancer, foreign tissue, fungal and viral infections, and parasites (Brannon & Feist, 2004).




                                                               


The classical model of the immune system is that it operates independently of the nervous system and psychological processes. However, researchers have demonstrated complex interactions among the central nervous system, endocrine system, and immune system, consistent with Green and Green's psychophysiological principle. Psychological processes like expectancies (placebo effect) and learning (classical conditioning) can affect all three systems and the immune system can affect psychological functioning (drowsiness from a fever). Psychoneuroimmunology is a multidisciplinary field that studies the interactions between behavior and these three systems.

After Solomon and Moos (1964) introduced the term psychoneuroimmunology in a journal article, Ader and Cohen's (1975) demonstration of classical conditioning in a rat's immune system helped establish this field's scientific legitimacy. Ader and Cohen trained rats to associate a  conditioned stimulus (a saccharine and water solution) with an unconditioned stimulus (the immunosuppressive drug cyclophosphamide). This resulted in a conditioned response (CR) of immune suppression which resulted in rat fatalities. Following conditioning, rats who only drank the sweetened water (CS) died due to conditioned immunosuppression. Successful replication of these findings helped overcome resistance to the controversial view that the nervous system and immune system can interact.

The mechanisms underlying these complex interactions may include hypothalamic-pituitary-adrenal (HPA) axis hormones like ACTH, cortisol, CRH, epinephrine, and norepinephrine, immune cell chemical messengers called cytokines (interleukins), hormones like androgens, estrogens, progesterone, and growth hormone, and neuropeptides like beta-endorphins.

There is persuasive evidence that stressful life events can reduce immunity and that behavioral interventions can enhance or maintain it. Bereavement can reduce lymphocyte (lymphatic white blood cell) proliferation (Schleifer et al., 1983). Academic exams, marital conflict, negative affect associated with stress, clinical and subclinical depression, and negative daily mood can suppress immunity (Herbert & Cohen, 1993; Kiecolt-Glaser et al., 2002; Stone et al., 1994).

The stress of living near the Three Mile Island nuclear plant when it experienced a major accident reduced residents' B cell, T cell, and natural killer cell counts when compared with control subjects (McKinnon et al., 1989).

A study of Alzheimer's caregivers showed lowered immunity and longer wound healing times and worse psychological and physical health than controls who were not caregivers (Kiecolt-Glaser, 1999) and that the Alzheimer's patients' deaths did not improve caregiver immunity or psychological functioning (Robinson-Whelen et al., 2001).

Finally, laboratory stressors produced greater discomfort and immunosuppression in chronically-stressed young males than those who were not chronically-stressed (Pike et al., 1994). Exposure to chronic stress may have intensified their subjects' response to acute laboratory stressors.

Behavioral interventions can increase immunocompetence. Miller and Cohen's (2001) meta-analytical study of behavioral interventions showed modest increases in immunity. Hypnosis increased immune function more than relaxation and stress management.

A stress management program that incorporated relaxation training reduced symptoms and increased salivary antibodies and psychological functioning in children diagnosed with frequent upper respiratory infections (Hewson-Bower & Drummond, 2001).

College students who wrote journal entries about highly stressful experiences increased lymphocyte proliferation and made fewer health center visits (Pennebaker, Kiecolt-Glaser, & Glaser, 1988). Smyth et al. (1999) asked asthma and rheumatoid arthritis patients to write journal entries about highly stressful experiences or planned daily activities. At four-month follow-up, 50% of the Pennebaker journal group who wrote about stressful experiences and 25% of the control group achieved clinically significant improvement in their immune-related disorders (Crider, 2004).

Dental and medical students who received hypnosis training maintained immune function while a control group showed declines in immunity (Kiecolt-Glaser et al., 2001). This suggests that behavioral interventions may be more effective in maintaining normal immunity than boosting immunity (Brannon & Feist, 2004).
 




Lazarus and Folkman's (1984) Transactional Model of Stress has more strongly influenced psychologists than Selye's General Adaptation Syndrome. While Selye's stimulus model theorized that stress is determined by events, Lazarus's cognitive model proposed that stress is determined by our perception of the situation.

In primary appraisal, we categorize the consequences of events as positive, neutral, or negative and determine whether an event is relevant and negative or potentially negative. We evaluate these events for their possible harm, threat, or challenge. Harm is damage that has already occurred. For example, a person who experiences a heart attack may perceive harm as damage to the heart muscle. Threat means damage that could occur in the future. The heart attack survivor may anticipate restricted physical activity and reduced income. The perception of an event as a threat has physiological consequences and can result in elevated blood pressure. Challenge is the potential to cope with the event and gain from this opportunity. The heart attack survivor may reframe this health crisis as an opportunity to make a career change. The perception of an event as a challenge can increase perceived self-efficacy, positive emotion, and lower blood pressure (Maier et al., 2003). The Chinese pictogram wei ji, which represents danger and opportunity, illustrates the negative and positive possibilities considered during primary appraisal.




During secondary appraisal, we evaluate whether our coping abilities and resources can surmount an event's harm, threat, or challenge. Lazarus and Folkman (1984) listed health and energy, positive belief, problem-solving skills, social skills, social support, and material resources as important coping resources. Again, perception of our coping abilities and resources is more important than their actual existence.

The balance between primary and secondary appraisal determines how we subjectively experience the event. We experience the most stress when perceived harm or threat are high and perceived coping abilities and resources are low. Stress is reduced when we perceive that our coping abilities and resources are high (Taylor, 2006).

Secondary appraisal can lead to our use of direct action, reappraisal, and palliation.

Direct action can take different forms depending on the nature of the threat. For violent threats to our survival, we may use aggression and escape behaviors from Cannon's fight-or-flight response. For medical or psychological threats, we may use problem solving, where we define the problem, identify options, and then test these options until we succeed. The cardiac patient may enroll in a cardiac rehabilitation program to increase exercise tolerance and reduce the risk of artery narrowing.

Reappraisal may reduce stress when direct action is impractical or unsuccessful. Reappraisal modifies our perception of a threat. When individuals are overwhelmed by traumatic stress, they may initially use ineffective strategies like denial and rationalization. As they cope with the crisis, they may progress with more successful strategies like reframing in which they place the stressful situation in perspective and focus on available opportunities. The cardiac patient may decide that his heart attack provided an opportunity to spend more time with his grandchildren.

Palliation consists of efforts to reduce our stress response rather than attack the stressor. Clinicians may use biofeedback and adjunctive techniques like effortless breathing to teach cardiac patients to control their anxiety. While this does not correct the cause of the stress response, it is often superior to medications like anxiolytics that risk side effects, tolerance, physical dependence, and withdrawal effects. Successful clinical interventions for chronic problems like anxiety, depression, and pain incorporate effective palliation since complete remission may be unlikely (Crider, 2004).


                                                    






Mastery overlaps with the concepts of locus of control, perceived control, and self-efficacy. Mastery is the relatively stable expectancy that we can control our personal outcomes. Mastery affects our appraisal and coping with stressors. Individuals with high levels of mastery expect to succeed when challenged by stressors, cope more effectively, and report lower levels of depression and stress than people with low levels of mastery (Gurung, 2006).

In Weiss’s (1977) replication of the Brady “executive monkey” study, the "executive” rat could switch off the tail shock by turning the wheel. Because it had control over the shock, it was no more likely to develop ulcers than an unshocked control rat. The "subordinate" rat received the same shocks as the "executive" rat. Because the "subordinate" rat had no control over the shocks, it was more likely to develop ulcers than the "executive" rat.



Hopelessness is a heart attack risk factor. Compared with Finnish middle-aged men scoring low in hopelessness, those scoring high were two to three times more vulnerable to a heart attack over the ensuing six years, and three to four times more likely to die (Everson et al., 1996).



Optimism is a generalized expectancy of positive future outcomes. Optimists focus on a situation's positive dimensions, minimizing daily hassles (Nelson et al., 1995).  Optimism aids health by encouraging more effective problem-focused coping strategies instead of avoidant coping strategies. This results in better stress management and practice of health-promoting behaviors like use of barrier protection during sex. Optimists show good psychological health, effective natural killer (NK) cell response during stress, and slower AIDS progression. In the context of the Transactional Model of Stress, optimists diverge from pessimists in secondary appraisal, actions, and personal adjustment (Gurung, 2006).



Pessimism is also a heart attack risk factor. A Harvard School of Public Health team found pessimistic adult men had a doubled risk of developing heart disease over a 10-year period (Kubzansky et al., 2001).



Wickramasekera (1988) described alexithymics, individuals who are low in hypnotic ability and awareness of internal cues and feelings associated with illness. Alexithymia is prevalent in patients with multiple psychosomatic complaints, and may delay their seeking and receiving medical attention.



Eliot's (1992) hot reactors cannot be identified by their overt behavior, but risk sudden death due to pathological acute and chronic responses to stressors. Hot reactors show an acute increase in catecholamine secretion, which increases the risk of cardiac arrhythmia due to excessive myocardial fiber contraction and clot formation. When they are challenged by long-term stressors and experience fear, uncertainty, and loss of control, they also show a chronic increase in glucocorticoid secretion, which raises total cholesterol while lowering protective HDL-C.



Social support consists of received support (support actually provided) and perceived support (expected support). Both forms of social support include informational, material, and psychological assistance from others. The value of each kind of social support depends on an individual's specific needs. Social network and social contacts both concern a person's number and kinds of interpersonal relationships. Individuals with a high level of social support participate in an extensive social network consisting of numerous social contacts. Those with low social support have a limited social network with few social contacts.

High levels of social support are associated with better health, faster recuperation, less psychological distress, lower depression risk, and lower mortality than low levels of social support (Gurung, 2006).

The Alameda County Study (Berkman & Syme, 1979) documented a relationship between number of social contacts and longevity. Adults with the fewest social contacts had 2-4 times the risk of death than those with the most social contacts. Gender and age moderated the effect of social contact. Males' highest relative risk of death (3.2) was from age 50-59, where women's highest relative risk (4.6) was from age 30-49 (Brannon & Feist, 2004).

Hawkley and colleagues (in press) reported that loneliness is an independent risk factor for hypertension that is comparable to obesity and sedentary lifestyle. They studied 229 participants aged 50 to 68 years and measured their perceived degree of loneliness, as well as previously established cardiovascular and psychosocial risk factors. Even after statistically controlling for the contribution of other negative emotional states (e.g., depression, hostility, or stress), lonely older participants had systolic blood pressures that were up to 30 mm Hg higher than their non-lonely counterparts. They discovered that loneliness and stress raised blood pressure via different mechanisms and that they produced an additive effect. Furthermore, the impact of loneliness on blood pressure increased with age.



Mildly depressed college women who participated in an aerobic exercise program showed markedly reduced depression, compared with those who did relaxation exercises or received no treatment (McCann & Holmes, 1984). A study that compared exercise with drug treatment or a combination of exercise and drug treatment found that exercise improved mood as well as the other two conditions. When treatment was discontinued, participants who continued to exercise were less likely to relapse than those who had received drug treatment (Babyak et al., 2000).

The positive impact of exercise on mood may be mediated by reduced cardiovascular reactivity (Perkins et al., 1986) , social involvement (Estabrooks & Carron, 1999), and an increased self-efficacy (McAuley et al., 2003), and self-esteem (Sonstroem, 1997).



In a national health survey financed by the U.S. Centers for Disease Control and Prevention, religiously active people had longer life expectancies (Hummer et al., 1999). McCullough and colleagues (2000) performed a meta-analysis that assigned greater weights to studies that controlled confounding variables like age, gender,  health, and social support. They found that religious involvement was linked to a slightly lower rate of mortality and that this was not due to social support.





Now that you have completed this module, identify your most critical stressors and coping resources. How does your personality moderate the effects of these stressors?



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