Stress Coping to Optimize Brain Function and Prevent Stress-

related Chronic Diseases

IHS, February, 23-25th, 2017

Overview

Prevalence of stress, adversity and trauma and effects on chronic diseases.Stress and trauma effects on brain cells, structure, functioning and behaviors.Clinical presentations of stress-related diseases affecting stress biology, symptoms to poor health outcomes.Introduction to experiential strategies to reduce stress and regain control over stress and coping.Integrative interventions to harness the brain’s resilient coping to improve health outcomes.

Stress Levels in the US and Anxiety Disorders

Yearly APA surveys show between 50 – 58% of Americans report being stressed or very stressed, including 38% of children – since 2005. (APA.org)

Close to 43% report having had 2 or more adverse childhood experiences (substance abuse or mental illness in home, verbal, physical or sexual abuse, family member in prison, witnessing domestic violence). (CDC, 2009)

Almost half of US men and women (48%) have experienced psychological aggression by an intimate partner in their lifetime (NIPSV Survey, 2011).

Lifetime prevalence of any anxiety disorders is 28.8% (Kessler et al., 2005).

Stress and Chronic Disease

Stress and Cardiovascular Disease50% increase in CVD risk linked to high levels of work stress

Stress and CancerStress affects antiviral defenses, DNA repair and cellular aging.Stress contributes to the initiation, growth, and metastasis of some tumors.

Health care expenditures 50% greater for those under stress.

Stress is also related to upper respiratory tract infections, asthma, herpes, viral infections, reduced immune response to vaccines,

autoimmune diseases, and slow wound healing

Stress and Metabolic DiseaseStress disrupts metabolic homeostasis • visceral obesity•type 2 diabetes•metabolic syndrome

CDC Report, 2005

Pirraglia PA, Hampton JM, Rosen AB, Witt WP. (2011) Am J Managed Care. May;17(5):319-28.

Stress and Healthcare Expenditures

Brain Disorders Leading to Highest Global Disease Burden

Amyotrophic lateral sclerosis (ALS)

Dementia

Alzheimer’s Disease

Parkinson’s

Multiple Sclerosis

Depression

Anxiety Disorders

Schizophrenia

Binge Drinking and Alcoholism

Substance addictions

Behavioral Addictions:

Binge eating

Binge technology use

Prince et al., Lancet, 2007

The First Target of STRESS is the Brain!!

Alcohol/Substance Abuse

Loss of loved one

Widowed

FinancialProblems

Overburdened by work!

Children’s illnesses

Divorce

Physical illness Isolation; loneliness

Victim of violence

Mental illness

The First Target of STRESS is the Brain..

Attention/awarenessEmotionality Physical function

- sleep; eating etc

Memory

Mood, AnxietyBehaviors, Choices, Decisions

Relationships

Mental flexibility, reasoning, openness Creativity

Problem Solving

What is Stress?Any stimulus or event that is:– Challenging– Threatening – Overwhelming – Uncontrollable– Unpredictable

Mental, emotional or physical stimulus

Increases a physical and psychological response to return our mind and body to baseline.

How do we know we are stressed?

COGNITIVE: Thoughts, attitudes, beliefs judgements, decisions, perseveration

BEHAVIORAL:Urges, actions, habits, stress-related eating, choices/responses

PHYSICAL:Sensations, energy, fatigue, sleep, health symptoms

EMOTIONAL:Emotions, feelings, moods,

Domains of Stress Experience:

Cognitive SymptomsMemory problems

Inability to concentrate

Poor judgmentPessimistic approach or thoughts

Anxious or racing thoughtsConstant worrying

Emotional SymptomsMoodiness

Irritability or short temperAgitation, inability to relax

Feeling overwhelmedSense of loneliness & isolation

Depression or general unhappiness

Physical SymptomsAches and pains

Diarrhea or constipationNausea, dizziness

Chest pain, rapid heartbeat

Loss of sex driveFrequent colds

Behavioral SymptomsEating more or less

Sleeping too much or too littleIsolating oneself from othersProcrastinating or neglecting

responsibilitiesUsing alcohol, cigarettes, or drugsNervous habits (eg nail biting, pacing)

Stress Signs and Symptoms

Corisol;Epi, NE

Weakend selfcontrol network

PFC

DigestiveOrgans

Heart

Lung

ParasympatheticNervous System (Ach)

HYPNAS

DANE

Activated by Stress & habits

Reduced by Stress & habits

Stress, CRF,Adrenaline

SympatheticNervous System (NE)

NegativeFeedback

Immune System- Increased

Pro-inflammatorycytokines

Stress Networks Involved in Adaptive Coping and Survival

Adapted from Capuron et al., 2006 and Sinha, 2008; 2013

NE and GC – NFKappaB

and TLRs

Taking Stock of Stress in Your Life

What Stresses You?

Your Pressure Points?

STRESS IS CRUCIAL FOR ADAPTATION AND SURVIVAL – BUT MILD/MODERATE LEVELS!

hypothalamus

pituitary

amygdala

prefrontal cortex

adrenal cortex

cortisol

adrenal medulla

norepinephrineepinephrine

sympathetic nervous system

parasympathetic nervous system

• increased energy• focused attention• improved working

memory, cognitive ability

• enhanced performance

Henderson, et al., 2012; Lupien & McEwen, 1997

FRONTAL BRAIN INVOLVED IN REGULATING STRESS

Cognitive/socialplanning; problem solving; setting goals; shifting and directing

attention (flexibility), validating self, seeking emotional and family support.

Distraction, avoidance/suppression, procrastination, rumination

BiologicalAutonomic and stress hormone mobilization (fight or flight

response) and inflammatory and anti-inflammatory responses

Behavioral running from dangerous situations; exercise, regular eating of healthy meals, take a walk, regular sleep (R&R), etc

Behaviors at risk for becoming bad habits: smoking, alcohol, taking drugs, overeating high fat foods, gambling, etc.

Arnsten et al., Scientific American, 2012; Sinha, Annals of NY Academy of Sciences, 2008

Brain Regulation of Stress & Behavior

Sinha, ANYAS, 2008; Arnsten, Nat. Neuroscience, 2009;

Thoughtful, flexible control of mind, body and behavior

When Stress Piles Up in Life…

The Cumulative Adversity Interview (CAI) is a 20 minute structured interview that asks about events experienced in lifetime, how often and first and last age of experiencing that event:

• Major Life Events: e.g. abandonment, divorce/separation, loss of child, parents substance abuse, relationship difficulties.

• Life Traumas: loss of home, witnessing or being in an accident, and in violent situations, sexual, physical and emotional abuse, being shot, assaulted, tortured, being in combat, losing someone to violence.

•Recent Life Events (past year): Accidents, illnesses, loss of child, trouble with law, pregnancies/abortion/miscarriages, school drop-out, financial crisis, school or work failures, work and relationship problems, living problems.

•Chronic Stressors: sense of being overwhelmed with life, unable to manage life problems, difficulties with job, living, finances relationships, conflicts, loneliness, unfulfilled desires, problems with children, living, etc.

High chronic stress reduces brain tissue in prefrontal neurons/regions that regulate stress

Ansell et al. (2012) Biol Psychiatry

Stress

Control

Stress-related neuronal atrophy in animals

Cumulative Stress related to lower brain volume in a community cohort (p<.001)

Radley et al. (2006) Cerebral Cortex

PFC

Striatum

Insula

Lupien S et al., Nature Neuroscience, 1998

Cortisol Levels and Effects on Brain Memory Region (Hippocampus) and Memory Problems in

Human Aging

Older individuals with lowerdaily cortisol levels:

Decreasing / Moderate Cortisol Group Increasing / High Cortisol Group

Older individuals with higherdaily cortisol levels:

14% SMALLER!

Turning attention to awareness of breath

The Brain is Highly Dynamic!

Can we protect our brain cells?

Seated Awareness of breath!

• breathe into your belly

• breathe into your chest

• breathe into your shoulders- upper chest

Decreasing

Stress

How can we Strengthen Mental Flexibility and Executive Control?

Prefrontal Executive and Attention Networks

Short-term (“scratch-pad”) memory;

Attention and self-regulation

Planning and problem solving based on future goals

Adaptive reasoning,Mental flexibility

Self-control over desires and impulsesEmotion regulation

Sociability/understanding of others

Consequences of High Persistent Stress:

Forgetfulness, experience of mind goes blank

Decreased conc/focus; increased distractibility

Disorganized impulsive behavior based on immediate needs

Narrowed or rigid thinking ‘tunnel vision’, perseverative thinking

Increased craving and habits

Heightened emotionality

Social withdrawal

Mental Check-in with the body…

What is your level of energy or fatigue?Are you hungry? Are you full? Are you neither?Are you too warm or too cold?How do your clothes feel? Are they comfortable or constricting? If you notice discomfort, where do you notice it?Without moving or changing, notice your posture. How are your legs positioned? What is the position of your arms? Where are your hands placed? Are you sitting up straight or slumped? Are you leaning against the back of your chair? Are your shoulders rounded forward? How is your head carried relative to your shoulders?In general, how comfortable is it to be in your body right now? (pause)As you thought about this question, did you notice any judgments arising in your mind about your body, the way you are dressed or any other aspect of your appearance?

Taking Hold of the Mind -Mindfulness

Paying attention in the moment

non-judgementally.

In “being“ mode – observing thoughts, feelings, sensations, urges and actions

Observe/notice and ‘letting go’ – bringing attention back to the moment or current focus.

Training and practice is key to Mindfulness based therapies

Increasing attention through observing …sensations,

thoughts, feelings, urges/actions

DESIRE

PLEASURE

REINFORCEMENT

REWARD

COMPULSION

Binge addictive behaviors stimulate stress pathways!

Binge alcohol use: Cortisol increases

Binge eating:

Binge technology use:

Cortisol increases

???

Stress eats up brain fuel: Promotes high calorie snacking

* * * * *

Z= -6 Z= -2 Z= 2

prefrontal cortex

Caudate/puatmen

prefrontal cortex

putamen

InsulaInsula

Hyp

ACC

R L

Z= -6 Z= -2 Z= 2

Stress of mild hypoglycemia increases preference and wanting of Highly

Palatable (HP) FoodsHypoglycemia (Hypo) compared to euglycemia (Eu) increases wanting of HP foods and brain response in craving, appetite and food reward regions (shown in blue) and decreases activity in prefrontal self control regions (in red) (p<.05 FWE corrected)

Page, Seo, de Aguiar, Constable, Sherwin, Sinha, Journal of Clinical Investigation (JCI), 2011

Cumulative Stress and Adversity is Associated with Smoking and Alcohol Abuse

(community adults) Total Stress By Smoking Status

Nonsmoker Smoker

Mea

n To

tal S

tres

s Sc

ore

20

22

24

26

28

30

Total Stress By Alcohol Use

Regular Binge Heavy Dependent

Mea

n To

tal S

tres

s Sc

ore

20

22

24

26

28

30

32

N=588 X2 = 31.66, df=1, P < 0.0001 OR =1.196 (1.124-1.273)

N=588X2 =15.37, df=1, P < 0.0001 OR =1.113 (1.055-1.173)

Sinha & Jastreboff, Biological Psychiatry, 2013

Cumulative Stress and Adversity is Associated with Obesity and Hypertension

N=560X2 = 6.46, df=1, P = 0.0110OR =1.19 (1.04-1.33)

Total Stress By BMI

Normal Overweight Obese

Mea

n To

tal S

tres

s Sc

ore

18

20

22

24

26

28

Total StressBy Blood Pressure

Normal PreHTN HTN

Mea

n To

tal S

tres

s Sc

ore

20

22

24

26

28

30

N=588X2 = 25.47, df=1, P < 0.0001 OR =1.146 (1.087-1.208)

Sinha & Jastreboff, Biological Psychiatry, 2013

High Cumulative adversity effects on metabolic measures and heart rate variability

Lampert et al., Stress, 2016; Sinha & Jastreboff, Biological Psychiatry, 2013

Stress Level and Risk of Colds

0

1

2

3

4

Rel

ativ

e R

isk

of a

Col

d

Duration of Life Stressor (in months)

no stressor < 1 > 1, < 6 > 6, < 24 > 24

25

30

35

40

45

50

3-4 5-6 7-8

9-10 11-12

Psychological Stress Index

% w

ith C

olds

New England Journal of Medicine, 1991 Cohen et al., Health Psychology(1998)

Symptoms of Stress:

•Feeling angry, irritable or easily frustrated

• Feeling overwhelmed

• Change in eating habits

• Problems concentrating

• Feeling nervous or anxious

•Trouble sleeping

• Problems with memory

• Feeling burned out by work

• Feeling down and overwhelmed

• More tension, aches and pains

• Low energy and fatigue

Enriching life through our senses!

Awareness of Sounds

THE DOUBLE JEOPARDY!RESETTING THE STRESSED BRAIN

1. Bring back frontal brain activity and normalizing it

2. Calming down the emotional and reward centers of the brain

Can we reverse these negative effects of stress on the brain, body and addictive behaviors?

– MedicationsPrazosinGuanfacine

– (Intuniv)

Arnsten et al., Scientific American, 2012; Arnsten, Nature Neuroscience Reviews, 2009

Luders E et al. (2009), Neuroimage.

Larger GM volumes in meditators (co-varied for age)Views of the right orbito-frontal cortex (left panel; p<0.0001uncorr), right thalamus (middle panel; p<0.0003uncorr), and left inferior temporal gyrus (right panel; p<0.0003uncorr), where GM is larger in meditators compared to controls. The color intensity represents T-statistic values at the voxel level. The results are visualized on the mean image derived from the 44 T1-weighted scans of the subjects analyzed, and presented in neurological convention (right is right).

Larger frontal and hippocampal (memory) gray matter volume with

meditation

Behavioral Strategies to Decrease Stress ReactivityBreath and relaxation training

Yoga

Regular exercise

Mindfulness and meditation training

Building in stress relieving activities and positive activities (it’s like “ money in the stress bank” for later unexpected challenges)

Psychotherapies– Dialectical Behavior Therapy (DBT)– Cognitive Behavioral Therapy– Behavioral Coaching in stress management

STAYING COOL! Stress Buffering and Resilience Factors

Social and Emotional Support (validating environment – family, peer and professional support)Positive attitude and hopeEnriching environment– mental stimulation – education, puzzles, memory

games– positive activities – hobbies, humor– regular physical activity, exercise, yoga– reduced exposure to addictive habitsRight brain stimulation – music, art, storiesCommunicating experiences – writing stories

• Morning and Night Building Reserve: - at least 5 minutes of seated awareness of breath.

• Pause – Reset: Resync your breath, mind and body: walking meditation; quiet time with your breath; e.g. making tea, positive activities.

• High stress and arousal: Observe the moment non-judgementally, acceptance of thoughts, feelings and urges.

• Compassion: for yourself and others too

Building Resilience in the Day:

PAYMENT: Contracts with Organizations; Many Services are Covered by Insurance (confidentiality is assured)

Contact: 203-737-3398; Web: yalestress.org; Email: stressvisit.edu

Yale Stress Center

Where the Science of Stress and Practice Come together – using an integrative approach with an interdisciplinary team of specialists and translational scientists.

Comprehensive stress wellness to optimize functioning - for the work place, individuals and families.

visit yalestress.org or Rajita.Sinha@yale.edu