Stress Across Life: Biological Correlates

Biological Correlates of Stress among Adults

Prof. Hani Hamed Dessoki, M.D.Psychiatry

Prof. Psychiatry

Chairman of Psychiatry Department

Beni Suef University

Supervisor of Psychiatry Department

El-Fayoum University

APA member

Biological Psychology

Stress

HISTORYHISTORY

Selye (1937) pioneered the field “Stress research”

Nonspecific, stereotypic responses to adverse conditions.

General adaptation syndrome.

Christian (1950s)Christian (1950s)

Relationship between stressors & population density.

Association between increased population density and activation of the pituitary-adrenal axis .

Since then, growing awareness of influence of stress on physiology and behavior.

Stress is an enescapable factStress is an enescapable fact of lifeof life

What is STRESS ?

Stress is a state resulting from events (stimuli) of external or internal origin, real or imagined that tend to affect the homeostatic state.

Stress and Health

Overview of Terminology

Stress: A state of disharmony or a threat to homeostasis

Physiological changes increase alertness, focus, and energy

Perceived demands may exceed the perceived resources

Coping: The ability to maintain control, think rationally, and problem solve

Resilience: Resistant quality that permits a person to recovery quickly and thrive in spite of adversity

Stress

EustressManageable Stress can lead to growth and enhanced competence

DistressUncontrollable, prolonged, or overwhelming stress is destructive.

Acute StressImmediate response to a threat or challenge

Chronic StressOngoing exposure to stress, may seem unrelenting

PhysicalPhysical

Events having direct physical threat.

Cold, heat,infection,

toxic substance, etc.

Psychological

Failure to achive goals.

Dath of loved ones,Job demands,interpersonal problems,financial problems, etc.

Stressful situation Psychological Stress

Sub-Types

Social : Financial problems, dominance , hierarchy insult, loss of self esteem.

Occupational : Work place problems, insufficient pay, uneasy relationship with coworkers.

Life stressors: Parking place problems, running late, dealing Spouse/children, divorce, isolation.

Philosophical/Spiritual : Meaning and purpose of life, belief in higher power, loss of values.

Physical and Psychological stressors are often intertwined.

© 2012 John Wiley & Sons, Inc. All rights reserved.

Seven Major Sources of Stress

STRESS RESPONSE

GASTROINTESTINAL 

METABOLIC 

CARDIOVASCULAR   

REPRODUCTIVE GROWTH AND REPAIR

IMMUNE

Digestion is inhibited (Enzyme action inhibited)

STRESS RESPONSE

METABOLIC CARDIOVASCULAR GASTRO INTESTINAL GROWTH & REPAIR IMMUNE REPRODUCTIVE

Increased heart rate and blood pressure to speed delivery of glucose and oxygen to tissues that need it

Digestion is inhibited (Enzyme action inhibited)

Inhibition of growth hormone and other anabolic processes

Depletion of lymphocytes (suppression of immune response)

Inhibition of reproductive functions

Triglycerides, glycogen and proteins are degraded and converted in to carbohydrates to provide immediate energy.

How these changes are induced ?How these changes are induced ?

CNS : Activation of Sympathetic nervous system, catecholamines excite cells/tissues. (Sympatho-adrenal system)

Endocrine: CRH, ACTH, Glucocorticoids, Adrenalin, vassopressin, endorphins.

Stress

Brain areas

Preganglionic

Fibers

Adrenal Medulla

Adrenalin

PVN

CRH/AVP

Pituitary

ACTH

Adrenal cortex

Glucocorticoids

Peripheral sites

B-endorphin

Behavior

What is the role of -endorphin?

A natural pain killer.

Inhibits synaptic transmission to prevent pain perception.

In the absence of -endorphin stress response exaggerated.

Stages of the Stress ResponseGeneral Adaptation Syndrome of Hans Selye (1907-1982)

Alarm—when one feels threatenedActivation of the fight or flight reaction

Resistance—mobilization of resources to solve the problem

Continued stress causes adaptation

ExhaustionAdaptation fails and level of function decreases

Models for Understanding StressThe General Adaptation Model

Allostasis

Maintaining stress and adaptive responses over the long term implies high levels of activation of the homeostatic processes

This causes wear and tear, called 'allostatic load'.See Selye's General Adaptation Syndrome diagram showing the level of endocrine response mounted:

Resting responselevel

Stress Paradox

ExhaustionBody is at depleted state

Must rest in order to recover

If stress continues without recovery or exhaustion =illness

perpetuation of illness

death

Stress and the Immune System

Psychoneuroimmunology

Interdisciplinary field that studies the effects of psychological and other factors on the immune system

The biological response to stress changes the activity of the immune system, increasing the risk of:Cancer

Periodontal Disease

Common Cold

Bursitis

Colitis

Rheumatoid Arthritis

Alzheimer’s

© 2012 John Wiley & Sons, Inc. All rights reserved.

Stress and Cognitive Functioning

Cortisol Effects on the Brain

SHORT TERM: Cortisol also can prevent the retrieval of existing memories, as well as the laying down of new memories

LONG TERM: Prolonged stress can permanently damage the hippocampus, a key part of the brain involved in memory. Once damaged, it cannot provide proper feedback to the hypothalamus, so cortisol continues to be secreted and a vicious cycle can develop

© 2012 John Wiley & Sons, Inc. All rights reserved.

Stahl S M, Essential Psychopharmacology (2000)

BDNF gene

StressStress

Stress

BDNF

Stahl S M, Essential Psychopharmacology (2000)

Apoptosis

Coping With Stress

Direct copingIntentional efforts to change an uncomfortable situation

ConfrontationAcknowledging stress directly and initiating a solution

CompromiseChoosing a more realistic goal when an ideal goal cannot be met

WithdrawalAvoiding a situation when other options are not practical

Notional model of emotions that arise fromthe balance between level of challenge and a person’s coping ability

Confidence

Challenge

apathyboredom

relaxation

control

engagement,flow

arousal

apprehension,anxiety

worry

high

highlowlow

The Role of Epigenetic Modulationin Major Depression and Schizophrenia

Champagne et al. 2005; Copyright Elsevier (2005).

Externalenvironment

Maternal careMaternal care Social experiencesSocial experiences

Geneticbackground

Geneticbackground

EARLY EXPERIENCESEpigenetic modifications 1

AdultFertilization Pre-natal Postpartum Post-weaning

REVERSIBILITYEpigenetic modifications 2

Behavioralphenotype

Stress and Ageing

Psychological stress is linked to oxidative damage of DNA and other cellular components Experimental Evidence

Study of Blackburn & her colleagues

Selected 58, normal, healthy mothers

19 Controls : Problem free children

39 Stress group: Chronically ill child

Blood samples were drawn and 3 parameters of cellular ageing analyzed:

1. Telomere length : Women with perceived stress had shorter

telomeres, extent of shortening was equal to

10 years of additional aging

2. Telomerase activity :

About 50% less in stressed women

3. Oxidative stress : Higher in stressed women

A telomere

A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos (τέλος) 'end' and merοs (μέρος, root: μερ-) 'part.' Telomere regions deter the degradation of genes near the ends of chromosomes by allowing chromosome ends to shorten, which necessarily occurs during chromosome replication.Without telomeres, the genomes would progressively lose information and be truncated after cell division because the synthesis of Okazaki fragments requires RNA primers attaching ahead on the lagging strand. Over time, due to each cell division, the telomere ends become shorter.

Telomeres

.

The study showed only an association between depression and shorter telomeres, and didn't prove a cause-and-effect link. The researchers said they aren't entirely sure what the shorter telomeres might mean in depression.

On one hand, study author Josine Verhoeven said, it could be that having shorter telomeres somehow sets a person up for mental troubles. But it's more likely that depression causes damage that leaves traces even at the cellular level, she said.

Depression is known to disrupt many physical systems. It alters hormones, suppresses the immune function and changes how nerves work. People with a history of depression have greater risks for diseases of aging, such as heart disease, type 2 diabetes, dementia and cancer.

"Results like ours suggest that psychological distress, as experienced by depressed persons, has a large, detrimental impact on the wear and tear of a person's body, resulting in accelerated biological aging," said Verhoeven, a doctoral researcher at VU University Medical Center in Amsterdam.

study was published online Nov. 12 in the journal Molecular Psychiatry.

One expert said the study is significant in the number of people it involved.

"The strength of this report is its size," said Etienne Sibille, an associate professor of psychiatry at the University of Pittsburgh. He is studying how depression ages the brain.

Sibille said previous research on the same question had mixed results -- probably because the studies were too limited to pick up the effect, which is small and varies from person to person.

"It's a small effect, but it's real," he said.

The next question science needs to answer, Sibille said, is whether telomere shortening really matters and if reversing it could improve health. Other studies have shown that a healthier diet, exercise and measures to control stress may lengthen telomeres.

"It's just not known whether it has an impact on cell function," he said. "If that's the case, it has potential therapeutic importance."

More information

Head to the U.S. Centers for Disease Control and Prevention for more on healthy aging.

SOURCES: Josine Verhoeven, doctoral researcher, VU University Medical Center, Amsterdam, Netherlands; Etienne Sibille, Ph.D., associate professor, department of psychiatry, University of Pittsburgh; Nov. 12, 2013, Molecular Psychiatry, online

Measuring YOUR Life Changes!

© 2012 John Wiley & Sons, Inc. All rights reserved.

Stress ManagementStress Management

1. Proper diet, exercise & relaxation.

Avoid hurry, Worry & curry.

2. Yoga: Flexing & bending of body parts along with controlled breathing does not cause fatigue like aerobic exercise.

3. Pranayama: Regulated deep breathing, rich

oxygen supply - relieves of stress.

4. Meditation: Relaxation of body & mind : reduces

excitation.

5. Accept reality, accept you can not change.

6. Avoid personal confrontation.

7. Humor: Takes sting out of stress.

8.Laughter: Physical & emotional effects :

Muscular activity burns calories,

reduces stress hormone levels,

increases endorphins, boosts

immunity.

9. Music : Soothing effect.

10. Sports, Games, Hobby.

Summary

"Stress reactivity is better understood as the result of intertwined biological and psychological processes that ultimately ensure an organism's survival.“

"There is a cost to frequent physiological adjustments (allostatic load)“

“One of the most interesting findings emerging from the research ... is that in the absence of supportive care, stressors experienced during sensitive periods of development can ... leave permanent imprints in the neural substrate of emotional and cognitive processes. ... the nervous system of mammals carries their singular epigenetic history and expresses it in unique but predictable ways”.