HOW OVER-ACTIVATION OF THE BODY AND BRAIN STRESS SYSTEMS CAN PREDICTABLY LEAD TO MENTAL HEALTH AND SUBSTANCE ABUSE PROBLEMS STEPHEN G.

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1 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

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 WHO IDENTIFIES STRESS AS THE HEALTH CARE EPIDEMIC OF THE 21 ST 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

4 Part 1. The Evolving Model of Stress

5 Pioneers in the Study of Stress Walter Cannon ( ) Hans Selye ( ) Homeostasis Fight or Flight Response Stress Response (HPA) General Adaptation Syndrome

6 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

7 Selye s General Adaptation Syndrome

8 STRESSOR PFC-HC-AM-HP ANS HPA Axis SNS + PNS - CRH+AVP SAM (RAPID RESPONSE) EPI+NE Increased Resp. ACTH Cortisol HPA (ONGOING RESPONSE) Increased Cardio Corticosterone Inc. Energy Release Immune + Inflam. Regulation Dec. Energy Storage Growth Inhibition Reproduction Inhib. Repair Inhibition

9 Effects of Stress on the Body

10 Three Types or Levels of Stress and Their Differential Effects on Physical and Mental Health Augments Function Requires Compensation Leads to Pathology

11 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)

12 AUGMENTING THE SIMPLE MODEL OF STRESS FOUR ADDITIONS ALLOSTASIS NEUROENDOCRINOLOGY INDIVIDUAL DIFFERENCES IN SHORT AND LONG-TERM RESPONSES TO STRESSORS EPIGENETICS

13 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

14 FEATURES OF ALLOSTASIS CHANGING SET POINT COMPENSATED EQUILIBRIUM EXTENSIVE ANTICIPATION OF DEMAND ADJUSTMENT BASED ON HISTORY

15 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

16 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

17 Individual Variation in Response to Stressors: A Multifactorial Problem

18 EPIGENETICS, STRESS AND MENTAL HEALTH

19 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 longterm effects on the stress systems

20 Part 2: Stress and Mental Health

21 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

22 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

23 VARIABLES THAT DETERMINE OUTCOME INDIVIDUAL DIFFERENCES AND VULNERABILITIES INTENSITY OF THE STRESSOR DURATION OF EXPOSURE TO THE STRESSOR

24 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

25 A THREE FACTOR MODEL FOR ESTIMATING LIKELIHOOD OF MENTAL HEALTH PROBLEMS SUBSEQUENT TO EXPOSURE TO STRESSORS 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) Low Robustness High Robustness Low Intensity High Intensity Low Intensity High Intensity Brief Extended. Brief Extended. Brief Extended. Brief Extended. Low to Moderate Risk Moderate to High Risk Moderate to High Risk High Risk Low Risk Moderate Risk Moderate Risk High Risk Depression/Anxiety Trauma/PTSD Depression/Anxiety Trauma/PTSD

26 STRESS AND THE OCCURRENCE OF PTSD AND ACUTE TRAUMA DISORDER

27 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

28 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

29 STRESS AND THE OCCURRENCE OF DEPRESSION AND ANXIETY

30 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 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 Generalized Anxiety Increased Anxiety or Worry Irritability Muscle Tension Restlessness Fatigue Poor Concentration Problems with Cognition Sleep Disturbance

31 THE DASS YIELDS SEPARATE SCORES FOR DEPRESSION, ANXIETY AND STRESS

32 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

33 Part 3: Stress and Substance Abuse

34 THE ADDICTION CYCLE

35 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

36 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

37 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

38 Part 4. Treatment Strategies

39 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

40 MONITORING PART 1 IDENTIFYING STRESSORS AND PERCEIVED STRESS 1. PTSD/ACUTE TRAUMA DISORDER RISK 2. COMMON STRESSORS 3. PERCEIVED STRESS 4. WORKPLACE STRESS

42 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

43 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.)

44 FIVE COMPONENTS OF STRESS MANAGEMENT 1. EDUCATION 2. IDENTIFICATION OF STRESSORS 3. PHYSIOLOGICAL STABILIZATION 4. SIMPLE SELF-REGULATION TECHNIQUES 5. LIFESTYLE MANAGEMENT

45 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

46 2. IDENTIFYING STRESSORS PHYSICAL MEDICAL SOCIAL ENVIRONMENTAL INTERPERSONAL OCCUPATIONAL

47 3. PHYSIOLOGICAL STABILIZATION REDUCE ALLOSTATIC LOAD 1. TREATMENT OF EXISTING CONDITIONS 2. TREATMENT OF INFECTIONS 3. SLEEP AND PAIN MANAGEMENT 4. DIETARY MANAGEMENT

48 4. SIMPLE SELF-REGULATION TECHNIQUES CONTROLLED BREATHING SIMPLE STRETCHING/TENSION REDUCING EXERCISES COGNITIVE RE-SETS

49 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)

The physiological response of stress

Master Biologie-Santé TC4 Stress and vulnerability to depression - An allostatic perspective Cyril Rivat Université de Montpellier cyril.rivat@umontpellier.fr The physiological response of stress Stress