Stress, Health & Disease

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Standard (traditional) Biomedical Model

Disease is a ‘disorder in an otherwise smooth-running machine’ (the body). 

• To cure it you must disrupt the causative agent at the physical level, allowing the machine (body) to repair itself and regain normal functio

Standard (traditional) Biomedical Model characteristics

1. One way causation: the pathogen acts on the host, not the other way around 

2. Non-hierarchal: the different levels of complexity in the system do not interact with each other

3. Disease and treatment work on physiology

4. Dualistic: sees the mind and body as separate which don’t work together for the individuals well being 

   • The cure works regardless of patients knowledge or assistance

Biopsychosocial model of Disease and Treatment (expanded biobehavioural model)

Looks at how biological, psychological, and social factors interact independently to maintain health or cause illness 

3 interactions of Biopsychosocial model of Disease and Treatment

1. Psychosocial processes: thoughts, emotions, and spoken words that interact with the socio-cultural environment 

2. Two-way interaction: the actions of the individual's immune system alter the pathogen and vise versa (exchange of information and learning from one another) 

3. Treatment: the treatment still alters the diseases state, but this model considers the pathogen, host and the social environment and psychosocial functioning as processes that affect treatment outcome

What is a placebo - 2 possible explanations

Fake treatment that looks like a real treatment but does not contain the active ingredient; operate and are able to elicit a “response” in the individual 

• 2 possibilities of explanation: expectations of the individual or conditioned associations

Psychoneuroimmunology (PNI)

Shows how classical conditioning alters immune functioning

Adler & Cohen rat experiment

• Gave mice immunosuppressive drugs dissolved in water, and once their immune systems had recovered they gave the rats water again (without the drug

  • found that the rats exhibited an impaired immune system in both situations.

Coronary Heart Disease (CHD)

Fatty plaques restrict oxygen to the heart

Traditional model on CHD

Focus on diet, genetics, cholesterol and surgical interventions

Expanded model of CHD

Includes type A behaviour (hostility, competitive drive, urgency) as they trigger frequent blood pressure elevations and stress hormones, accelerating plaque formation 

Psychological theory on disease

A disorder of body functions or systems arising from malfunction at the level of physiological, psychophysiological or sociocultural functioning

Behavioural medicine

• The study of how sociocultural and mind-brain processes can influence the health of an individual. 

  • Identifies ways that maladaptive behaviours, states of mind or cultural practices may impair health and how these same processes can be used to improve it

Systems theory (Gary Schwartz)

How systems are regulated and how they maintain that regulation when threatened with disruption

5 stage model to represent systems theory hierarchally

1. Two-way (organism-environment) dialogue: body and external environment interact to maintain internal balance  (environment through our actions)

2. Mind-brain integration: brain processes both external and internal cues to determine regulation of the somatic organs  

3. Somatic adaptation: organs alter their functions based on brain signals (maintaining an optimal balanced internal environment)

4. Interoceptive feedback: brain uses internal feedback to make automatic, subconscious adjustments

5. External biofeedback: the brain sometimes uses external sources of information to regulate the body

Biofeedback

Monitoring sensors (eg heartbeat, skin temperature, etc) to measure normally involuntary unconscious bodily functions

Greek world view

Divided the world into a physical one, (changeable), perceived through senses, and a world of pure form (eternal), can only be reached by reason alone

Plato's world view

Elaborated the Greek world view and proposed 4 classes of reality: 

1. The shadows: how we perceive objects 

2. True objects: actual physical items in the material world

3. Sciences: numbers, geometric figures, and scientific hypotheses

4. Pure forms: true essence of things, what gives things meaning

Metaphysics & 2 core principles

Study of fundamental nature of reality 

• 2 core principles: 

1. 1 single, material level of physical reality exists

2. Physical world has external permanency that nonmaterial (mental) activities cannot alter

5 major premises of modern science

1. Reductionism: complex phenomena understood by studying their simplest parts

2. Mechanism: living things are studied using the same rules that govern mechanical objects

3. Causality: every observed phenomenon has a physical cause

4. Determinism: everything is determined by a complex of physical causes

5. Dualism: humans possess two distinct natures (physical and mental)

Mind-body dualism in disease

The body works as a machine

• Diseases are disorders in a smooth-running machine, and a cure disrupts causative agents at the physical levels (the machine repairs itself) 

Vitalism

Living organisms are alive due to a unique  (non-physical) "life force" that physics and chemistry alone cannot explain

Bernard

Rejected vitalism, arguing instead that biological phenomena are governed by strict, determinable physicochemical laws

Walter Cannon

Built upon Bernard’s ideas and called the process of maintaining internal stability in the face of environmental change homeostasis

Homeostasis

The body maintains its own balance

Allostasis

The ongoing effort required to maintain homeostasis when the stressor persists

Allostatic load

Prolonged stress consumes so much energy that the body can eventually become exhausted and health can deteriorate

Stressor

Any event with possible (physical or psychological) threat to the attainment of psychobiological goals

Transient (acute) stressor

A stressful event that happens once and lasts a short time

Repeated/chronic stressor

A stressful situation that happens repeatedly or lasts for a long time

Stress response

Adaptive psychobiological reaction to a stressor aimed to eliminate the threat

Stress

Imbalance between stressor demands and coping possibilities (resources) → appraisal of perceived threat

Stress equation

Severity of stress is determined by the size of the challenging force minus the body's capacity to compensate

Mental arithmetic task (Brod)

Mental calculations under observation by an experimenter create mental effort and mild stress

Hans Selye

The first person to invoke systematically the concept of stress as a means to understand physiological regulatory responses to threats to the organism

• Explored how animals reacted to various challenges to their homeostasis

The general adaptation syndrome (Hans Selye)

A three-stage physiological process that describes how your body reacts to stress:

1. Alarm reaction: fight or flight

2. Resistance: body tries to adapt to ongoing stress and repair itself 

3. Exhaustion: after long-term chronic stress the individuals physical and mental resources are completely drained

Transactional Model of Stress and Coping (Lazarus and Folkman)

Stress occurs when a person perceives that a situation is demanding and exceeds their ability to cope with it

• Primary appraisal: personal meaning of event, is the situation a threat, a challenge, or irrelevant

• Secondary appraisal: personal belief of capacity to reduce the stressor by considering internal and external resources and coping potential 

  • Coping: how to manage the situation or feelings about it

  • Reappraisal: reassessing the situation based on what happens and how the individual copes

Basal psychological factors that determine threat value (appraisal) and the effects of stress on the body

1. Adversity (nature of threat): physical/ psychological

2. Uncontrollability and unpredictability: in punishment or reward

3. Duration: longer duration = greater impact 

Perseverative cognition

Anticipation to potential future stressors which may cause unlimited "prolongation" of stressors or frequent response to stressors that often do not occur (these responses are no longer functional)

Yerkes-Dodson Law

Describes the relationship between arousal (activation) and performance as an inverted U-curve where performance increases with mental / physical arousal up to an optimal point, after which higher arousal causes performance to decline

• Too low arousal: poor performance (too little focus, drowsiness) 

• Optimal arousal: maximum performance

• Too high arousal: deteriorating performance (panic reactions, tunnel vision)

3 levels of stress conceptualisation

• Environment: the stressor itself 

• Appraisal: how threatening/stressful the person receives it to be

• Response: emotional/physiological response

Kagan (2016) view on term “stress”

Stress is used too broadly; should only refer to events that pose a serious threat to well-being

Stressnology

Problematic and primitive approach to studying effects of life stress exposure on health

2 systems that cause fight-or-flight response to stress

Sympathetic-adrenal-medullary (SAM) system & hypothalamic-pituitary-adrenal (HPA) system

Sympathetic-adrenal-medullary (SAM) system steps

Immediate stress responds (lasts seconds & intense)

1. Threat detected: amygdala signals hypothalamus

2. SNS activated: releases noradrenaline onto organs and signals adrenal medulla to release adrenaline into the blood

3. Fight-or-flight response: body prepares to respond (eg. increased heart rate and blood flow to muscles)

Hypothalamic-pituitary-adrenal (HPA) system steps

Sustained stress response (lasts minutes & slow) 

1. Threat detected: amygdala signals hypothalamus

2. Hypothalamus: releases CRF & vasopressin, which signals the pituitary gland

3. Pituitary gland: releases ACTH into the blood.

4. Adrenal cortex: ACTH triggers release of cortisol, which provides sustained energy by mobilising fat/protein and increasing glucose

5. Effects: suppresses immune and non-essential activities, reduces inflammation and pain, and helps limit tissue damage from the SAM response

6. Negative feedback loop: rising levels of cortisol signals hypothalamus + pituitary gland to stop releasing stress hormones (ACTH + CRF) and return to homeostasis

Reactivity hypothesis - heightened & lowered cortisol response

Greater stress reactivity causes greater future health risk

• Heightened cortisol response: hypertension, coronary artery calcification, future cardiovascular risk, shorter telomeres

• Lowered (blunted) cortisol response: chronic stress, obesity, depression, anxiety

Diurnal cortisol rhythm

Consists of the cortisol awakening response and diurnal cortisol slope

Cortisol awakening response (CAR)

Steep increase in cortisol during 30-45 minutes after waking

Diurnal cortisol slope

Diminishing levels of cortisol throughout the day

Stress-related circadian dysregulation (SCiD)

Stress-induced disruption of circadian biology across multiple coregulatory systems

Autonomic nervous system (ANS)

Controls automatic body functions (e.g., heart rate, breathing and digestion).

Branches: sympathetic nervous system (SNS) & parasympathetic nervous system (PNS)

Sympathetic nervous system (SNS)

Part of ANS that governs energy mobilization and fight-or-flight arousal

Parasympathetic nervous system (PNS)

Part of ANS that governs rest, digestion, restorative and vegetative functions

Baroreflex

Pressure-sensitive carotid and aortic receptors detects changes in blood pressure

• the brain adjusts sympathetic / parasympathetic to regulate blood pressure

Perseverative cognition

Repeated thinking about stress (e.g., worry, rumination) that keeps the body’s stress response activated, prolonging physiological arousal

Prevailing state model

Individuals under chronic stress exhibit a permanently elevated baseline of physiological functioning in everyday life

Generalized Unsafety Theory of Stress (GUTS)

Proposes that fight-or-flight response is the body's default state turned off only by recognition of safety

Heart rate variability (HRV)

Variation in time intervals between consecutive heartbeats

• Low = autonomic imbalance = elevated cardiovascular risk

Nocturnal blood pressure dipping

Normal physiological drop in blood pressure and heart rate during sleep

Conserved transcriptional response to adversity (CTRA)

Gene expression pattern triggered by chronic stress, causing increased inflammation and reduced antiviral and antibody responses

Glucocortoid resistance hypothesis

Chronic stress makes immune cells less sensitive to cortisol, causing ongoing low-level inflammation despite high cortisol levels

Major challenges in stress-health research (3)

• Measuring stress: stress is unpredictable 

• Controlling pathogen exposure: to determine whether stress increases infectious disease risk, studies must ensure stress presence + pathogen exposure

• Measuring clinically meaningful results: inability to reflect coordinated, whole-body immune responses to natural pathogens

Viral challenge studies (Cohen et al)- stress & cold findings

• Higher chronic stress (especially work/interpersonal stress lasting >1 month) → higher risk of developing a cold

• Social support (eg., social integration, hugging) reduces illness risk; sleep, exercise and smoking also affect risk

Vaccine challenge studies (Glaser et al) - stress & vaccine findings

• Students experiencing high stress and anxiety produced fewer antibodies after hepatitis B vaccination

• Chronic stress may weaken vaccine effectiveness, leaving people less protected against infections

Lovallo’s frontolimbic model

Early-life adversity alters brain development, leading to reduced stress reactivity, impulsivity and unstable emotion regulation, increasing substance abuse risk and unhealthy behaviours

Thalamus function & damage result

Relays sensory information to the brain

Damage: causes loss of vision, altered pain sensation, cognitive deficits, speech deficits, motor problems and sensitivity loss

Hippocampus function & damage result

Forms and stores new memories

Damage: leads to inability to form new long-term memories

Amygdala function & damage result

Processes emotions, especially fear and threats

Damage: severely affects classical conditioning

Ventromedial PFC (vmPFC)

Regulates emotions and helps make decisions

Damage: causes emotions to be situationally inappropriate

Acute stress

Short-term (seconds / weeks) physiological + psychological reaction to sudden, perceived, or terrifying threat

Acute episodic stress

Frequent or constant occurrence of acute stress

Chronic stress

Continuous, long-term (months / years) state of physical or psychological tension caused by ongoing pressures, conflicts, or threats

• Increases CVD, stroke, metabolic syndrome, and cancer risk factors

Adaptive stress

Healthy, short-term physiological and psychological reaction that helps the body handle a challenge and then return to a calm state

INTERHEAT study results

Found that psychological stress in the preceding year was associated with more than twice the risk of myocardial infarction after adjustment for conventional cardiovascular risk factors

What happenes in the brain & body when a threat is detected?

1. The amygdala stimulates the hypothalamus 

2. There is an increase  in sympathetic nervous system (SNS) activity 

3. There is a decrease in parasympathetic nervous system (PNS) activity 

4. The hypothalamic-pituitary-adrenal axis (HPA axis) is activated 

5. Behaviour is influenced through connections with the periaqueductal gray

Takotsubo syndrome

A temporary weakening of the heart muscle, often triggered by severe emotional or physical stress (“broken heart syndrome”)

• Associated with altered brain structure/connectivity in stress-related regions (e.g., amygdala) and increased inflammation

The prefrontal cortex helps calm down your body's threat/stress response through regulating…. (6)

• Amygdala → reduces the feeling of threat/fear

• Brainstem → reduces automatic defensive responses

• Autonomic nervous system → calms things like heart rate and breathing

• HPA axis → reduces the release of stress hormones such as cortisol

• Anterior cingulate cortex (ACC) → helps monitor/regulate emotional responses

• Hippocampus → provides context (“Is this actually dangerous?”) and helps regulate the stress response

Stress-induced immune dysregulation & effect on ANS

• Chronic stress shifts the immune system towards increased inflammation but weaker antiviral defence

• Stress effect on ANS: 

  • Increases SNS activity: increases heart rate, blood pressure and vascular resistance

  • Suppresses PNS activity: reducing heart-rate variability

How stress increases inflammation

• Norepinephrine activates adrenergic receptors → increases white blood cell (leukocyte) production in bone marrow and inflammatory cytokines (eg. IL-6)

• Norepinephrine reduces CXCL12 (keeps white blood cells in bone marrow) → more inflammatory cells enter the bloodstream, promoting plaque buildup (atherosclerosis)

How stress weakens antiviral defence

Glucocorticoids and catecholamines suppress antiviral gene activity → reduced antiviral protection and greater vulnerability to infections

Effects of stress on blood vessels

Inflammatory cells enter artery walls → endothelial dysfunction, abnormal blood vessel responses, increased blood clotting and inflammation in atherosclerotic plaques

Neural–immune–arterial pathway

Chronic stress → increased amygdala activity → increased white blood cell production (leukopoiesis) → arterial inflammation → increased CVD risk

Psychometric questionnaires to measure stress

Measure stress through an individual's perceived emotional response

Physiological measurements to measure stress

• Skin conductance for sympathetic activity 

• Heart-rate variability for parasympathetic activity 

• Blood or urinary catecholamines for sympathetic activation 

• Glucocorticoids, CRH, ACTH, or vasopressin in blood, urine, saliva or hair for HPA-axis activity

Neuroimaging methods to measure stress - fMRI

Measures neural activation and connectivity in response (typically amygdala activation) to rapidly changing stimuli

Neuroimaging methods to measure stress - F-FDG PET/CT

Measure metabolic activity in the brain and other tissues

Neuroimaging methods to measure stress - Combined PET & MRI

Simultaneously assess brain structure, functional activation, resting metabolism, bone-marrow activity, and arterial inflammation

Antidepressants and ketamine as a stress intervention

Reduce amygdala activity and downstream effects 

SSRIs as a stress intervention

Improve depressive symptoms and may reduce recurrent cardiovascular risk in patients with depression and established CVD

Beta -blockers as a stress intervention

May reduce sympathetic nervous system-driven leukopoiesis

Anti-inflammatory drugs such as canakinumab as a stress intervention

May directly reduce proinflammatory cytokine activity

Stains as a stress intervention

May decrease arterial inflammation and subsequent cardiovascular events

Physical stressor

Challenges that threaten bodily integrity and homeostasis through direct physical force or metabolic strain

Bottom-up activation

Physiological responses to physical stressors initiated in peripheral tissues (working muscles, respiratory system) → sends ascending neural & chemical signals to brainstem control centres

Psychological stressors

Challenges that alter bodily function and health based on the cognitive meaning, interpretation, and perceived long-term consequences of an event

Top-down activation

Physiological responses to psychological stressors initiated in higher cortical + limbic centres → sends descending neural + endocrine signals to hypothalamus and brainstem (cardiovascular) centres

The exercise response stages

Preparatory phase (top-down activation) & active phase of exercise (bottom-up activation)

Preparatory phase (top-down activation) - exercise response

Before exercise, the brain activates the SNS, suppresses the PNS and releases adrenaline to prepare the body. Blood pressure can rise due to baroreflex inhibition

Baroreflex inhibition

Brain temporarily suppresses the blood pressure reflex, allowing blood pressure to rise during exercise

Active phase of exercise (bottom-up activation) - exercise response

During exercise, muscle feedback increases SNS activity and heart rate. Blood flow is redistributed to working muscles.