Stressors and the Stress

Response

HOW OVER-ACTIVATION OF THE BODY AND BRAIN

STRESS SYSTEMS CAN PREDICTABLY LEAD TO

MENTAL HEALTH AND SUBSTANCE ABUSE PROBLEMS

STEPHEN G. HOLLIDAY, PHD

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WHO IDENTIFIES STRESS AS THE

HEALTH CARE EPIDEMIC OF THE 21ST

CENTURY• 50% OF PEOPLE IN THE WORKFORCE STATE THAT STRESS NEGATIVELY EFFECTS

PRODUCTIVITY

• JOB STRESS IS ASSOCIATED WITH OBESITY, ADDICTION, ANXIETY AND HEART

DISEASE

• WARS AND DISASTERS HAVE LED TO UNPRECEDENTED NUMBERS OF CASES OF

POST TRAUMATIC STRESS DISORDER (PTSD)

• STRESS IS ASSOCIATED WITH INCREASED INCIDENCE RATES OF DEPRESSION

AND ANXIETY

• ROCKETING RATES OF SUBSTANCE ABUSE ARE THOUGHT TO BE RELATED TO

INCREASED LEVELS OF STRESS

Part 1. The Evolving Model of Stress

Pioneers in the Study of Stress

Walter Cannon (1871-1945)

Homeostasis

Fight or Flight Response

Hans Selye (1907 – 1982)

Stress Response (HPA)

General Adaptation Syndrome

Homeostasis

THE PROCESS(ES) THAT LIVING ORGANISMS USE TO ACTIVELY MAINTAIN THE STABLE PHYSIOLOGICAL CONDITIONS NECESSARY FOR SURVIVAL

THE NORMAL VALUE OF A PHYSIOLOGICAL VARIABLE IS CALLED ITS SET POINT

THE HUMAN BODY MAINTAINS STEADY LEVELS OF TEMPERATURE AND OTHER VITAL CONDITIONS SUCH AS THE WATER, SALT, SUGAR, PROTEIN, FAT, CALCIUM AND OXYGEN CONTENTS OF THE BLOOD

Selye’s General Adaptation Syndrome

PFC-HC-AM-HP

ANS HPA Axis

Increased Resp.

PNS - CRH+AVPSNS +

EPI+NE

Cortisol

Immune + Inflam. Regulation

Corticosterone

ACTH

Growth Inhibition

Inc. Energy Release

Dec. Energy Storage

Increased Cardio

Reproduction –Inhib. Repair Inhibition

STRESSOR

SAM

(RAPID

RESPONSE)

HPA

(ONGOING

RESPONSE)

Effects of Stress on the Body

Three Types or

Levels of Stress

and Their

Differential Effects

on Physical and

Mental Health

Augments

Function

Requires

Compensation

Leads to

Pathology

A SIMPLE MODEL OF STRESS

• STRESSORS ACTIVATE PHYSIOLOGICAL SYSTEMS IN PREDICTABLE AND

CHARACTERISTIC WAYS (THE STRESS RESPONSE)

• ACTIVATION DISRUPTS/AUGMENTS NORMAL PHYSIOLOGICAL FUNCTION

(HOMEOSTATIC DYSREGULATION)

• ACTIVATION HAS PREDICTABLE IMMEDIATE ADAPTIVE CONSEQUENCES (FIGHT

OR FLIGHT RESPONSE)

• SHORT-TERM ACTIVATION IS FOLLOWED BY A RETURN TO THE NORMAL RANGE OF

FUNCTION (HOMEOSTASIS

• LONG TERM ACTIVATION HAS DETRIMENTAL PHYSIOLOGICAL CONSEQUENCES

(GENERAL ADAPTATION SYNDROME)

AUGMENTING THE SIMPLE MODEL

OF STRESS – FOUR ADDITIONS

• ALLOSTASIS

• NEUROENDOCRINOLOGY

• INDIVIDUAL DIFFERENCES IN SHORT AND

LONG-TERM RESPONSES TO STRESSORS

• EPIGENETICS

ALLOSTASIS

• AN ADAPTIVE PHYSIOLOGICAL RESPONSE THAT ORGANISMS

ACTIVATE WHEN HOMEOSTASIS IS DISRUPTED

• ALLOSTATIC PROCESSES ALTER METABOLIC FUNCTION VIA

COMPENSATORY/ANTICIPATORY MECHANISMS IN RESPONSE TO

INTERNAL OR EXTERNAL CUES/STIMULI (STRESSORS)

• ALLOSTATIC PROCESSES ALLOW THE BODY SYSTEMS TO ADAPTIVELY

ADJUST TO CONSTANTLY CHANGING ENVIRONMENTS

FEATURES OF ALLOSTASIS

• CHANGING SET POINT

• COMPENSATED EQUILIBRIUM

• EXTENSIVE ANTICIPATION OF DEMAND

• ADJUSTMENT BASED ON HISTORY

Allostatic Load

The Physiological Price of Adaptation that Organisms Pay

When Allostatic Process are Repeatedly Activated or When

Activation is Maintained Over Extended Periods of Time

BRAIN SYSTEMS UNDER STRESS

BRAIN SYSTEM LOW-MODERATE

INTENSITY STRESS

HIGH/EXTREME

INTENSITY STRESS

PFC and Hippocampus + Density of Dendrites and

Synapses

+Neurogenesis

- In Density of Dendrites and

Synapses

- Neurogenesis

Amygdala - In Density of Dendrites and

Synapses

- Neurogenesis

+ In Density of Dendrites

and Synapses

+ Neurogenesis

Nucleus Accumbens + Dopamine Release - Dopamine Release

Individual Variation in Response to Stressors:

A Multifactorial Problem

EPIGENETICS, STRESS AND MENTAL HEALTH

A LESS SIMPLE MODEL OF STRESS

Stressors activate the body/brain stress systems

Specific responses are associated with particular types of stressors

Allostatic processes come into play when the stress system is activated

Long-term activation of the stress systems leads to allostatic overload

The response to CONTINUED allostatic overload is organ/system

dysfunction/failure

Individual differences play a role in stress response and adaptation

Exposure to stressors can lead to phenotype changes that have long-

term effects on the stress systems

Part 2: Stress and Mental Health

STRESS AND MENTAL HEALTH

EXPOSURE TO STRESSORS CAN HAVE PROFOUND

EFFECTS ON MENTAL HEALTH

• MOOD DISORDERS

• ANXIETY DISORDERS

• POST TRAUMATIC STRESS DISORDERS

• TRAUMA-BASED DISORDERS

TWO DISTINCT SITUATIONS & OUTCMES

1. BRIEF OR PROLONGED EXPOSURE TO HIGH-INTENSITY STRESSORS

Post Traumatic Stress Disorders

Acute Trauma Disorders

Complex Trauma Disorders

2. PROLONGED EXPOSURE TO LOW/MODERATE-INTENSITY STRESSORS

Anxiety Disorders

Depression/Mood Disorders

VARIABLES THAT DETERMINE OUTCOME

• INDIVIDUAL DIFFERENCES AND VULNERABILITIES

• INTENSITY OF THE STRESSOR

• DURATION OF EXPOSURE TO THE STRESSOR

THE TWO DIMENSIONS OF ROBUSTNESS

1. RESISTANCE

ENDURANCE IN THE FACE OF BOTH GREATER INTENSITY

STRESSORS AND LONGER DURATION OF EXPOSURE TO STRESSORS

2. RESILIENCE

FASTER AND MORE EFFICIENT RECOVERY OF FUNCTION OR FASTER

AND MORE EFFICIENT RETURN TO NORMAL SET POINTS FOLLOWING

EXPOSURE TO STRESSORS

Low Robustness

High IntensityLow Intensity

Extended.

Moderate Risk

High Robustness

Brief

Moderate Risk

Low Risk

High Risk

Low to Moderate Risk

Factor 1. Physiological & Psychological Robustness (Low vs. High)Factor 2. Intensity of the Stressor (Low vs. High)

Factor 3. Duration of Exposure to the Stressor (Brief vs. Extended)

A THREE FACTOR MODEL FOR ESTIMATING LIKELIHOOD OF MENTAL HEALTH PROBLEMS SUBSEQUENT TO EXPOSURE TO STRESSORS

Low Intensity High Intensity

BriefBriefBrief Extended.Extended.Extended.

High Risk

Moderate to HighRisk

Moderate to HighRisk

Depression/Anxiety Depression/AnxietyTrauma/PTSD Trauma/PTSD

STRESS AND THE OCCURRENCE OF

PTSD AND ACUTE TRAUMA DISORDER

DSM V - PTSD

THERE ARE NOW FOUR SYMPTOM CLUSTERS

1. RE-EXPERIENCING THE EVENT

1. Spontaneous memories, flashbacks, dreams

2. HEIGHTENED AROUSAL

1. Hyper-vigilance, reckless behaviour, sleep disturbance

3. AVOIDANCE

1. Distressing memories, thoughts or feelings of the event

4. NEGATIVE THOUGHTS/MOOD/FEELINGS

1. Distorted sense of blame, diminished activities, estrangement

PTSD: A SIMPLE STRESS-FOCUSED MODEL

• EXPOSURE TO A HIGH INTENSITY STIMULI EVOKES A STRONG STRESS RESPONSE (AMYGDALA/HIPPOCAMPUS ETC.)

• INITIAL MEMORIES/RESPONSES OCCUR VIA CLASSICAL CONDITIONING (FLASH MEMORIES OF HIGH INTENSITY)

• SUBSEQUENT RESPONSES OCCUR VIA COGNITIVE/EMOTIONAL EVALUATIVE PROCESSES (TRADITIONAL LEARNING)

• RE-EXPOSURE TO INTERNALLY OR EXTERNALLY GENERATED STIMULI STRENGTHENS BOTH TYPES OF LEARNING

• THE TWO SOURCES OF MEMORY PLAY OFF OF EACH OTHER LEADING TO STRENGTHENING OF THE VARIOUS RESPONSES LEADING TO ONGOING TRIGGERING OF A) THE STRESS RESPONSE AND B) THE COGNITIVE/EMOTIONAL RESPONSE

STRESS AND THE OCCURRENCE OF

DEPRESSION AND ANXIETY

Symptom Overlap

Depression

Feeling Sad, Empty, Hopeless

Decreased Pleasure or Interest

Loss of appetite/Weight Loss

Sense of Worthlessness or Guilt

Thoughts of Death

Agitation or Retardation

Fatigue / Loss of Energy

Poor Concentration

Problems with Cognition

Insomnia or Hypersomnia

Generalized Anxiety

Increased Anxiety or Worry

Irritability

Muscle Tension

Restlessness

Fatigue

Poor Concentration

Problems with Cognition

Sleep Disturbance

Stress

THE NON-SPECIFIC SYMPTOMS THAT ARE A PART OF THE DIAGNOSTIC CRITERIA OF THE VARIOUS VERSIONS OF THE DSM ARE REMARKABLY SIMILAR TO THE PHYSIOLOGICAL RESPONSES THAT OCCUR WHEN PEOPLE ARE EXPOSED TO MODERATE INTENSITY STRESSORS FOR LONG PERIODS OF TIME

THE DASS YIELDS SEPARATE

SCORES FOR DEPRESSION,

ANXIETY AND STRESS

DEPRESSION AND ANXIETY – STRESS

EXPOSURE END-STATES?

• LONG TERM EXPOSURE TO LOW/MODERATE INTENSITY STRESSORS LEADS TO ALLOSTATIC OVERLOAD IN VULNERABLE INDIVIDUALS

• PHYSIOLOGICAL OVER-AROUSAL LEADS TO EMOTIONAL AND PHYSICAL DESTABILILZATION

• OVER-ACTIVATION OF THE EMOTIONAL NETWORKS LEADS TO ANXIETY SYMPTOMS

• UNDER-ACTIVATION OF THE EMOTIONAL/BEHAVIOURAL NETWORKS LEADS TO DEPRESSIVE SYMPTOMS

• INDIVIDUAL VARIATION AND VULNERABILITIES DETERMINE SPECIFIC OUTCOMES

Part 3: Stress and Substance Abuse

THE

ADDICTION

CYCLE

FEATURES OF THE ADDICTION CYCLE

1. A PATHOLOGICAL CHANGE IN THE HOMEOSTATIC MECHANISMS THAT REGULATE EMOTIONAL STATES

2. CHRONIC ELEVATION OF THE REWARD SET-POINTS LEADING TO EMOTIONAL AND COGNITIVE DISREGULATION

3. LOSS OF EXECUTIVE CONTROL LEADING TO IMPULSIVITY AND POOR BEHAVIOURAL REGULATION

4. COMPROMISE OF THE BRAIN ANTI-STRESS SYSTEMS WHICH CONTRIBUTED TO COGNITIVE AND EMOTIONAL DYSFUNCTION

SPECIFIC WAYS THE STRESS RESPONSE

CONTRIBUTES TO SUBSTANCE ABUSE

INITIAL STAGES/ACQUISITION

• ALL ADDICTIVE SUBSTANCES ARE ACUTE PHYSICAL STRESSORS/NEUROTOXINS

• ACUTE STRESSORS TRIGGER AUGMENTED LEARNING (CLASSICAL CONDITIONING)

• STRESS IS ASOCIATED WITH DISREGULATION OF DOPAMINE FUNCTION

• INCREASED ALLOSTATIC LOAD LEADS TO DISRUPTION OF COGNITIVE AND EMOTIONAL STATES

LATER STAGES/MAINTENANCE

• CHRONIC HPA ELEVATION LEADS TO CHRONICALLY DE-REGULATED COGNITIVE, EMOTIONAL

PROCESSES (BRAIN EFFECT)

• CHRONIC ALLOSTATIC LOAD LEADS TO EMERGENT HEALTH PROBLEMS (BODY EFFECT)

• CLASSICALLY CONDITIONED CUES TRIGGER CRAVINGS AND RELAPSE

IMPLICATIONS FOR TREATMENT

1. WITHDRAWAL MANAGEMENT MUST INCLUDE SPECIFIC EMPHASIS ON

DECREASING ALLOSTATIC OVERLOAD AND ASSOCIATED

PHYSICAL/EMOTIONAL/COGNITIVE PROBLEMS

2. TREATMENT MUST CONSIDER THE LEARNING PROCESSES THAT

UNDERLIE ADDICTIVE BEHAVIOUR

3. SELF-MANAGEMENT STRATEGIES MUST INCLUDE BOTH SIMPLE AND

COMPLEX STRESS MANAGEMENT TECHNIQUES

Part 4. Treatment Strategies

THE CASE FOR ROUTINE MONITORING

OF STRESSORS AND STRESS LEVELS

• OVERACTIVE BODY AND BRAIN STRESS SYSTEMS ARE

ASSOCIATED WITH NEGATIVE CLINICAL OUTCOMES

• REGULAR MONITORING CAN ALERT CLINICIANS TO RISKS

INCLUDING ALLOSTATIC LOAD

• FOLLOW-UP WITH STRESS-MANAGEMENT TECHNIQUES CAN

REDUCE ALLOSTATIC LOAD AND ASSOCIATED HEALTH RISKS

MONITORING PART 1

IDENTIFYING STRESSORS AND PERCEIVED STRESS

1. PTSD/ACUTE TRAUMA DISORDER RISK

2. COMMON STRESSORS

3. PERCEIVED STRESS

4. WORKPLACE STRESS

MONITORING PART 2

USING BIOMARKERS/ ALLOSTATIC LOAD INDICES

Primary Mediators: Cortisol, Epinephrine, Norepinephrine, DHEAS

Secondary Outcomes: Systolic and Diastolic BP, Waist-Hip Ratio,

High-Density Lipoprotein and Total Cholesterol Ratio, Glycosylated

Haemoglobin

USING COMPOSITE INDICES AND

SUMMARY SCORES

A SUMMARY SCORE IS MORE PREDICTIVE OF HEALTH SCORES THAN IS A

SINGLE VALUE OR VARIABLE

THERE IS NO AGREEMENT ON WHICH BIOMARKERS SHOULD BE USED TO

CREATE COMPOSITE SCORES.

THERE IS NOT YET A STANDARD FOR EVALUATING RISK (SIMPLE COUNT

VS CUTOFF VS QUARTILE VS Z-SCORES ETC.)

FIVE COMPONENTS OF STRESS

MANAGEMENT

1. EDUCATION

2. IDENTIFICATION OF STRESSORS

3. PHYSIOLOGICAL STABILIZATION

4. SIMPLE SELF-REGULATION TECHNIQUES

5. LIFESTYLE MANAGEMENT

1. EDUCATION

1. OVERVIEW OF THE MODERN MODEL OF STRESS

2. DISTINGUISH BETWEEN STRESSORS AND THE STRESS RESPONSE

3. APPRECIATE THE SHORT AND LONG-TERM EFFECTS OF STRESS

4. UNDERSTAND DIFFERENT TYPES OF STRESS CONTROL

2. IDENTIFYING STRESSORS

PHYSICAL

MEDICAL

SOCIAL

ENVIRONMENTAL

INTERPERSONAL

OCCUPATIONAL

3. PHYSIOLOGICAL STABILIZATION

REDUCE ALLOSTATIC LOAD

1. TREATMENT OF EXISTING CONDITIONS

2. TREATMENT OF INFECTIONS

3. SLEEP AND PAIN MANAGEMENT

4. DIETARY MANAGEMENT

4. SIMPLE SELF-REGULATION TECHNIQUES

CONTROLLED BREATHING

SIMPLE STRETCHING/TENSION REDUCING EXERCISES

COGNITIVE RE-SETS

5. LIFESTYLE MANAGEMENT

BUILDING STRESS-BUSTING ROUTINES (IN THE MOMENT)

ADDING STRESS-REDUCING ACTIVITIES (THE BIG PICTURE)

MANAGING EXPOSURE TO STRESSORS (CONTROL YOUR LIFE)

DEALING WITH PHYSICAL CONSEQUENCES (WORK WITH YOUR MD)