The Lifelong Effects of Early Adversity and Toxic Stress

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The Lifelong Effects of Early Adversity and Toxic
Stress

• Jim Bien, MD, FAAP
• IU Health Arnett

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CME Disclosure

• I have no actual or potential conflict of
  interest in relation to this program/presentation
  .

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Objectives

1. Understand the concept of Adverse Childhood
   Experiences (ACEs) and their cumulative impact on
   long-term health.
2. Be familiar with the characterization of stress
   responses as positive, tolerable, and toxic and
   understand the factors related to these
   descriptions.

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Objectives

1. Know that brain development is characterized by
   time periods where vulnerability to stress is
   particularly sensitive, and that the presence of
   a stable adult relationship is the most
   protective factor in helping to mitigate harm
   during these times.

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Objectives

1. Appreciate the amount of adult disease burden
   related to early life traumatic experiences
2. Consider the role for screening for ACEs in adult
   patients by adult medical practices.

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Agenda

• Review the sentinel 1998 ACE study by Vincent
  Felitti and Robert Anda, along with subsequent
  studies building on their work.
• Review development of the CNS and the physiology
  of the human stress response, in particular the
  concept of a toxic stress response
• Conclude with a consideration for the role of
  screening for ACEs in the medical care of adults.

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American Journal of Preventive Medicine
199814245-258
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Categories of ACEs from Felitti and Anda
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ACE Study Participant Demographics
Demographic Categories Demographic Categories Percent (N 17,337)
Gender Gender Gender
  Female 54
  Male 46
Race Race Race
  White 74.8
  Hispanic/Latino 11.2
  Asian/Pacific Islander 7.2
  African-American 4.6
  Other 1.9
Age (years) Age (years) Age (years)
  19-29 5.3
  30-39 9.8
  40-49 18.6
  50-59 19.9
  60 and over 46.4
Education Education Education
  Not High School Graduate 7.2
  High School Graduate 17.6
  Some College 35.9
  College Graduate or Higher 39.3
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ACE Studys Percent with ACEs
ACE Score Total
0 36.1
1 26.0
2 15.9
3 9.5
4 or more 12.5
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Prevalence of Individual ACEs
ACE Category Women ()(N 9,367) Men ()(N 7,970) Total ()(N 17,337)
 Emotional Abuse 13.1 7.6 10.6
 Physical Abuse 27.0 29.9 28.3
 Sexual Abuse 24.7 16.0 20.7
 Emotional Neglect 16.7 12.4 14.8
 Physical Neglect 9.2 10.7 9.9
 Mother Treated Violently 13.7 11.5 12.7
 Household Substance Abuse 29.5 23.8 26.9
 Household Mental Illness 23.3 14.8 19.4
 Parental Separation or Divorce 24.5 21.8 23.3
 Incarcerated Household Member 5.2 4.1 4.7
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Possible Risk Outcomes from ACEs
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ACEs and Odds Ratio Depression
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ACEs and OR Smoking
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ACEs and OR Alcoholic
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ACEs OR IV Drug Use
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ACEs and O.R. Ever Attempted Suicide
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ACEs Odds Ratio Promiscuity
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Additional Findings for those with 4 ACEs

• 2.2 times as likely to have Ischemic Heart
  Disease
• 1.9 times as likely to have any cancer diagnosis
• 2.4 times as likely to have had a stroke
• 3.9 times as likely to have chronic lung disease
• 1.6 times as likely to have diabetes

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ACEs Impact on Mortality

• In a follow-up study the original ACE researchers
  found
• Adults with 6 ACEs died nearly 20 years earlier
  than those without ACEs (60.6 yrs vs 79.1 yrs)
• Adults with 6 ACEs were
• 1.7 times more likely to die when aged 75 yrs,
• 2.4 times more likely to die when aged 65 yrs.
• (Am J Prev Med 200937(5)389-396)

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Child Abuse Neglect 35 (2011) 408-13
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ACEs and OR of Adol Pregnancy(Pediatrics Vol 113
No. 2 Feb 2004)
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Additional research has expanded on ACE Study
Findings

• 2015 Kerker et al
• poor early childhood mental health and
• chronic medical conditions, and
• social development
• 2013 Reavis et al
• adult criminal behavior
• 2015 Wing et al
• pediatric asthma

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ACEs Negatively Impact Lives

• The conclusion from this growing body of research
  is that certain early life experiences are major
  risk factors for the leading causes of illness
  and death as well as poor quality of life in the
  United States.
• Why?
• For that we need to look a bit at brain
  development and the stress response

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Review of Brain Development

• At birth, most neurons the brain will have are
  present, approx. 100 billion neurons
• Neuron connections stimulated by experience
• Tremendous overproduction in neuronal connections
  in first years of life (700/second)
• approx. 1000 trillion connections by age 3 yrs.
• Selective reduction of neurons and connections
  among neurons PRUNING
• Pathways that are nurtured are strengthened and
  sustained

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Synapse density over time
Source Corel, JL. The postnatal development of
the human cerebral cortex. Cambridge, MA Harvard
University Press 1975.
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Sequential Development of Functions
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Core Concepts of Brain Development

• Occurs prenatally through adulthood
• First basic neural circuits are built, and then
  more complex
• There are critical periods of brain development
  require stimulation, and periods of development
  where the brain is most sensitive to stimulation.
• The brain is optimally flexible and plastic early
  in life, but as it develops and refines its
  circuitry, it looses much of its flexibility.

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Core Concepts of Brain Development

• The interaction between genetics, the
  environment, and experience shapes brain
  architecture.
• Genetics provides the plan
• Environment enables expression of the potential
  of the genetic plan
• Experience is the interaction of the child with
  the environment
• The brain is designed to be responsive to our
  experiences experiences literally influence the
  formation of its circuitry.
• Serve and Return activities promote development.

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Neurobiology Amygdala

• Input from sensory, memory and attention centers
• Emotional memory system The brains alarm system

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Neurobiology Hippocampus

• Interface between cortex and lower brain areas.
• Major role in memory and learning.
• The brains file cabinet or search engine.

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Neurobiology Frontal Cortex

• Executive functions
• Impulse control
• Working memory
• Cognitive flexibility
• Attentional Control

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Stress Response The HPA Axis

• Stress activates
• Release of epinephrine and cortisol.
• Stimulates multiple areas of body and immune
  system.

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Positive Stress Response
1

• Brief increases in heart rate
• Mild elevations of stress hormones
• Examples
• Dropping off at Day Camp
• Losing a soccer game
• Overcoming fear of swimming
• Possible consequences Development of a sense of
  mastery that is critical for healthy development

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Tolerable Stress Response
2

• More prolonged activation of the stress response
  system
• Examples
• A summer away from home
• Death of a loved one
• Persistent discrimination
• Frightening accident
• Possible consequences
• Range from positive to harmful depending on
  relationships, the environment, prior
  experiences, and innate factors

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Toxic Stress Response
3

• Prolonged activation of stress response systems
• Examples
• Physical or emotional abuse
• Chronic neglect
• Exposure to violence
• Extreme poverty
• Possible consequences Lifelong impacts on brain
  architecture and other parts of the bodys
  stress response system that increase the risk of
  stress-related physical and mental illness
  later in life

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Toxic Stress definition

• The excessive or prolonged activation of the
  physiologic stress response systems in the
  absence of the buffering protection afforded by
  stable, responsive relationships.

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ACEs Trigger Toxic Stress Responses
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Toxic Stress Impacts Multiple Systems

• Neurologic
• HPA Dysregulation
• Reward Center Dysregulation
• Hippocampal neurotoxicity
• Neurotransmitter and receptor dysregulation
• Immunologic
• Increased inflammatory mediators
• Altered microbiome
• Too much cortisol suppresses immunity, increasing
  risk of infection
• Inflammatory response persists after it is no
  longer needed

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Toxic Stress Impacts Multiple Systems

• Endocrine
• Long-term changes in cortisol, adrenaline
• Epigenetic
• Differential gene expression of pro-inflammatory
  transcription factors and neurotransmitter
  receptors
• Changes in way DNA is read and expressed. Brain
  stress response is altered

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Bottom Line for Brain Development
When children experience stable nurturing
relationships, they foster the development of
healthy circuitry. When children experience
unstable, traumatic, abusive or neglectful
relationships, they disrupt the circuitry of the
brains architecture as its being built.
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What do some of the responses to trauma look like
throughout childhood?

• Impacts on Working Memory
• Difficulty acquiring developmental milestones
• School skill acquisition difficulty
• Confabulation to make up for deficits
• Impact on Inhibitory Control
• Tantrums, aggressiveness, poor attachment
• Peer difficulties, disruptive
• Impulsive actions threaten health and well-being
• Impact on Cognitive Flexibility
• Frustration intolerance
• Disorganization, inattention, distractible,
  learning problems
• Difficulty assuming more complex tasks work
  duties, driving

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What do some of the responses to trauma look like
throughout childhood?

• Impacts on Bodily Functions
• Sleep
• Difficulty falling asleep
• Difficulty staying asleep
• Nightmares
• Eating
• Rapid eating
• Lack of satiety
• Anorexia
• Toileting
• Encopresis, enuresis, regression of skills

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What do some of the responses to trauma look like
throughout childhood?

• Toxic stress leads to maladaptive responses of
  the stress response system
• May remain excessively anxious long after a real
  threat has passed,
• May feel threatened or anxious even when no real
  threat is present
• May misinterpret facial expressions as hostile or
  anger when they are actually neutral

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Maladaptive behaviors as a way to cope

• What may be viewed as a problem is actually a
  solution to bad experiences.
• Dismissing these as bad habits or self
  destructive behavior misses their functionality.
• Alcohol, Nicotine and other drug use
• Sexual promiscuity
• Overeating/eating disorders
• Delinquent behavior

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The theory of ACEs Lifelong Impact
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Influencing Pediatric Practice

• Adverse childhood experiences are the single
  greatest unaddressed public health threat facing
  our Nation today.
• Robert Block, MD, FAAP
• Past President, AAP

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Influencing Pediatric PracticePEDIATRICS Volume
129, Number 1, Jan 2012
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The Basic Science of Pediatrics
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EBD Framework for Pediatrics

• An EBD approach recognizes that it is not
  adversity alone that predicts poor outcomes. It
  is the absence or insufficiency of protective
  relationships that reinforce healthy adaptations
  to stress, which, in the presence of significant
  adversity, leads to disruptive physiologic
  responses (toxic stress) that produce biological
  memories that increase the risk of
  health-threatening behaviors and frank disease in
  life.

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AAP Policy Recommendations

1. Psychosocial problems should no longer be viewed
   as categorically different from the causes and
   consequences of other biologically based health
   impairments.
2. The scientific knowledge of ACEs and toxic stress
   should be fully incorporated into all levels of
   pediatric training.
3. Pediatricians should adopt a more proactive
   leadership role in educating families, child care
   professionals, teachers about toxic stress.

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AAP Policy Recommendations

• Pediatricians should be advocates for the
  development and implementation of evidence-based
  interventions that reduce sources of toxic stress
  and or mitigate their effects.
• Pediatric Medical Homes should
• Strengthen anticipatory guidance re development
• Actively screen for precipitants of toxic stress
• Participate in adaptations that expand their
  ability to support children at risk
• Identify or advocate for local resources that
  address risks for toxic stress.

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Positive Assn Between Parental ACE and Child
Adversity
JAMA Pediatrics August 2015 Vol 169, 8,786-787
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In light of this science,

• Should we be screening adults for traumatic
  childhood experiences?
• If we screen, what are we to make of the results?
  
• How does treatment become modified by the new
  knowledge?
• Impact on parents as it relates to the
  environments their children are experiencing
• Impact on management and care of their own health

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What About Adult Practice?

• Some practices are testing screening adults for
  ACEs
• Felitti at Kaiser Permanente
• Screening questionnaire filled out at home.
• Example questions
• Have you been sexually molested as a child or
  adolescent?
• Have you been physically abused as a child?
• Who in your family has been murdered?
• Who in your family has been alcoholic or a drug
  user?

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Adult Screening at Kaiser

• Felitti found patients willing to share these
  details. It becomes an enormous relief to find
  people are interested and willing to listen.
• Analysis of 100K patient evaluations over two
  years of comprehensive screening found in the
  following year
• 35 reduction in physician office visits
• 11 reduction in emergency department visits
• 3 reduction in hospitalizations

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Others concur with this approach.

• collecting information about exposures to ACEs
  offers an opportunity to develop a plan of care
  for patients that is better informed, provides
  more context in relation to the patients health
  histories, and strives to improve health outcomes
  and patient satisfaction.
• - Screening and Case Finding for Adverse
  Childhood Experiences Annie Lewis-OConnor, PhD,
  NP-BC, MPH Nadine Burke-Harris, MD, MPH and
  Susan McCormick-Hadley, PhD, MPH
• http//www.avahealth.org/aces_best_practices/scree
  ning-and-case-finding.html

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Screening Questioned as Option
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Select References

• Technical Report. The Lifelong Effects of Early
  Childhood Adversity and Toxic Stress. Pediatrics
  vol. 129 no. 1 e232-e246
• Relationship of childhood abuse and household
  dysfunction to many of the leading causes of
  death in adults. The Adverse Childhood
  Experiences (ACE) Study. Am J Prev Med. 1998
  May14(4)245-58
• http//developingchild.harvard.edu/
• http//www.centerforyouthwellness.org
• http//www.rwjf.org/en/library/collections/aces.ht
  ml
• http//www.acestoohigh.com