Medical Effects of Chronic Stress Jeffrey P Schaefer MSc MD FRCPC November 17, 2015

dr.schaeferville. com

Conflicts of Interest none

Objectives Participants will... –define stress and learn its ingredients –gain an understanding of stress physiology –consider clinical implications –consider remedies

Case 42 year old female –weight loss (20 kg / 9 months) –poor appetite, nausea, insomnia –no medication, no tobacco, no alcohol, married exam normal labs all normal imaging including pan CT, GI, normal colonoscopy endoscopy normal Diagnostic Procedure?

Case Resolution Q: “What happened in your life around the time you became unwell?” A: “My sister was diagnosed with lymphoma and my mother got deported from Canada.” Q: “Is it possible that these events caused you to lose your appetite? A: “I’ve never thought about that before... is that possible?”

Objectives Participants will... –define stress and learn its ingredients –gain an understanding of stress physiology –consider clinical implications –consider remedies

Stress...

Acute Stress Response Fight, Fright, Flight, Frolic

Hans Selye ( ) Stress “Non-specific response of the body to any demand for change”

decons truct acute stress

Stress Stimuli

Experience the Stimuli

Physiological Response Hormones Neurochemistry Immunochemistry Metabolism

Experience of the Physiological Response

Good Stress (absolute stress)

Eustress Gap between have and want is just beyond... Motivating!

Relative Stress Interpretation of the world

Hans Selye ( ) General Adaptation Response –Alarm –Failure to adapt –Exhaustion

Stress & Recovery

Allostatic Load

Recipe for Stress Novelty Unpredictability Threat to ego Loss of control

Objectives Participants will... –define stress and learn its ingredients –gain an understanding of stress physiology –consider clinical implications –consider remedies

Stress Hormones Corticosteroids –Cortisol Catecholamines –Adrenaline –Nor-adrenaline

Cortisol Regulation Brain –emotion, pain, memory Hypothalamus –autonomic function Pituitary –stimulating hormone Adrenal Gland –cortex

Happy Sad Disgust Mind Body Connection: neural and hormonal

Immediate Effects of Cortisol Response to Absolute Stress –increase vigilance –respond to emotion  don’t think –raise blood sugar –increase psychomotor activity –obtain food

Prolonged Effects of Cortisol increase appetite increase blood sugar increase fat stores redistribute fat salt retention  BP + reduce acid barrier menstrual cycle problems male impotence bone calcium loss muscle wasting insomnia irritability depressed mood memory loss* immune dysfunction

Catecholamines Adrenaline (Epinephrine) Nor-adrenaline (Nor-epinephrine)

Effects of Catecholamines increase heart rate increase cardiac force of contraction narrows blood vessels increase blood pressure dilates pupils dilates airways reduces flow of blood to GI tract reduces saliva production increases platelet adherence ‘stickiness’ increases sweat production

Stress also... stimulates –Vasopressin release  ACTH –Growth Hormone release (depletes in chronic) suppresses –insulin production –gonadotropins –suppresses TSH

Objectives Participants will... –define stress and learn its ingredients –gain an understanding of stress physiology –consider clinical implications –consider remedies

Acute Stress and MI Mortality in Widowers –40% increase within 6 mo of spouses death Myocardial Infarction Onset Study –incidence of AMI 14X among recent widows / widowers

Self-report AMI Trigger 412 reports from 849 AMI

Cardiovascular Disease: 3.1 ( ) Coronary Heart Disease: 3.5 ( ) Myocardial Infarction: 6.4 (1.8 – 22.3)

Psychobiological Framework

Non-Stressed Mice: 32 tumours Stressed Mice: 84 tumours Non-Stressed Mice: 32 tumours Stressed Mice: 84 tumours

RR Persistent Positive Depression = 1.34 (1.01 – 1.76)

Mice  8 months of stress

Sperm Concentration: – 38% Sperm Count:– 32% Semen Volume: – 15% Nov 2015 Sperm Concentration: – 38% Sperm Count:– 32% Semen Volume: – 15% Nov 2015

Chronic Stress & Immune Dysfunction Influenza Vaccination Difference between stressed and non- stressed group. –Lancet 1999

Wound Healing

Punch Biopsies 13 Care Givers vs 13 Controls Complete wound healing –Caregivers 48.7 vs 39.3 days (9 day diff) –Age and income did not effect outcome

Medically Unexplained Symptoms Physical symptoms that prompt the sufferer to seek health care but remain unexplained after an appropriate medical evaluation.

MUS Prevalence 30% of primary care visits 13.6 visits in the previous year Psychosomatic Med 2005;67:123-9

Highest Frequency Clinics GI 54% Neuro50% Rheum33% ENT27% GIM10%

Medically Unexplained Conditions Non-CardiacChest Pain Headache Syndromes Fibromyalgia Irritable BowelChronic Fatigue Infertility Dizziness

Do functional symptoms cluster in a way that support multiple conditions? –Cross sectional survey of patients with functional symptoms –Screened 2,300 patients  978 were judged functional

Median Number of Symptoms Men  4 Women  6 Men & Women  5

“Bodily Distress Disorder” Fink et al. Psychosom Med 2007 Chest Pain Group GI Symptoms Group Musculoskeletal Group < 3% of patients had symptoms confined to their predominant group 3 group model explained 36% of the variance

Chronic Fatigue Syndrome Fibromyalgia Irritable Bowel Syndrome Multiple Chem Sensitivity Syndrome Sick Building Syndrome Hypoglycemia Gulf War Syndrome Undocumented Labels Headache Syndromes Asthma Painful Conditions Various Bodily Distress Disorder

So now what?

Objectives Participants will... –define stress and learn its ingredients –gain an understanding of stress physiology –consider clinical implications –consider remedies

Recognize the Source of Stress Novelty Unpredictability Threat to Ego Sense of Loss of Control Have a Plan B

n=109 Chronic Pain Clinic Patients randomized: Mindfulness Meditation (8 weeks) Wait List 33 completed / 54 meditation 40 completed / 55 wait list

Unhappiness is… Patients Feel Unheard –physician centered approach 69% of MD’s interrupt at 18 sec into the interview Ann Int Med 1984:101 –physician patient incongruence longer the patient talks  more likely to prescribe Psychosomatic Med 2007;69:571-7 – Why reassurance fails? PLOS Medicine 2006

MUSDepressedControls P(Disease)15%10%5% 25

Goodwill Mother Theresa Effect –improved self-esteem

CMBM Approach symptoms are psychobiological –real & explainable & diagnosable management –cognitive reassurance is insufficient –uncovering a psychological trauma is insufficient –psychotropic medications are counterproductive –success lays in self-regulation

290 patients

Objectives Participants will... –define stress and learn its ingredients –gain an understanding of stress physiology –consider clinical implications –consider remedies