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Effect of Abuse and
Neglect on Brain
Development
Michael D De Bellis, MD, MPH
Marilyn Kaufhold, MD, FAAP
Learning Objectives
The participant will be able to:
• Define the term developmental traumatology.
• Summarize evidence that shows the effect of
early life stress on the biologic stress response
system in maltreated children.
• Compare and contrast brain development in
healthy versus maltreated children.
• List circumstances capable of attenuating or
accentuating the effects of maltreatment.
Developmental Traumatology
Systematic
investigation of
the
neurobiological
impact of chronic
interpersonal
violence on the
developing child
A new field that
draws from
• Developmental
psychopathology
• Developmental
neuroscience
• Stress and
trauma research
Goals of Developmental
Traumatology Research
Improved
understanding of
risk and resiliency
in maltreated
children
Improved
interventions for
maltreatment
victims and those
at risk
Review: The Normal Biological
Stress Response System
Mediated
by four
interacting
systems
• HPA: Hypothalamic-pituitaryadrenal axis
• LC/NA: locus coeruleus
noradrenergic neurotransmitter
system
• ANS: Autonomic nervous
system
• Immune system
Child abuse activates the biologic
stress response system
• Threatening external stimuli are processed through the
thalamus which
• Activates the amygdala fear detection circuit
• Amygdala transmits
signals to the basal
forebrain,
paraventricular nucleus
of the hypothalamus
and brainstem
HPA Axis
• Hypothalamus secretes
corticotrophin-releasing
hormone (CRH)
• CRH binds to receptors in the
anterior pituitary gland,
stimulating release of
adrenocorticotropic hormone
(ACTH)
•
ACTH binds to receptors in
the adrenal cortex
• Adrenal cortex secretes cortisol
Heulens (2011)
Cortisol binds to receptors
throughout the body to…
• Suppress the immune system
• Stimulate gluconeogenesis
• Regulate the stress response system:
• Attenuate stress response by
binding to receptors in the mPFC
• Promote stress response by binding
to amygdala receptors
• Inhibit release of CRH by the
hypothalamus
• Inhibit the release of ACTH by the
pituitary
Sternberg (2006)
HPA, LC/NA,
ANS
• CRH activates the LC/NA
• LC releases increased
amounts of norepineprine
• Elevated arousal,
vigilance, anxiety
• LC/NA activates the sympathetic nervous system
• Increases heart rate/BP/sweating/muscle tone
• Redistributes blood away from the skin, intestines,
and kidney to the heart, brain, and skeletal muscle
The Biological Stress Response
System in Maltreated Children
Research in child abuse victims shows:
• Baseline cortisol levels are higher in maltreated
children
• With PTSD as manifested by symptoms of
anxiety and depression
• In sexually abused girls
• With significant internalizing symptoms
• Plasma ACTH responses to cortisol are attenuated
• HPA axis hyper-responds
LC/NA, ANS and Immune System
in Maltreated Children Produce…
Elevated
heart rate
Immune
system
suppression
Impaired
growth
Metabolic
syndrome
Decreased
alpha 2 –
adrenergic
receptors
Elevated 24-hour
excretion of
catecholeamine
metabolites
Hypertension
Review: Healthy Brain
Development
Steady
increase in
intracranial
volume
until age 10
• Overproduction of neurons
in utero
• Increases in neuron size and
synapses during childhood
• Apoptosis: selective pruning
of many neurons
• Increase in myelination
during adolescence and
young adulthood
Brain Development in
Maltreated Children
Increased levels of catecholamines and cortisol
lead to adverse brain development through…
Accelerated loss of neurons (premature aging)
Delay in myelination
Abnormalities in normal pruning
Neurogenesis inhibition
Cerebral Cortex, Corpus Callosum
and Cerebellum
MRI Studies of healthy brains vs. those of maltreated
children show…
• Size reduction in portions of the corpus callosum
• Decrease in white, not grey, matter in the brain
(depending on area and age of child may see
decrease in both)
• Increased size of ventricles (males only)
• Decreased intracranial volume by 7%
• Decreased total brain volume by 8%
• Smaller cerebellar volume
Changes correlate with duration/severity of abuse
The Limbic System: Emotion
and Memory Changes
• Amygdala activates the stress
response – CA victims show…
• Exaggerated startle response
• Enhanced fear conditioning
• Hippocampus is responsible
for biological stress system,
especially contextual memory
– CA victims show…
• Impaired neural integrity
Morris, Charles G., Psychology: An Introduction, 8th Edition, © 1996. Reprinted
by permission of Pearson Education, Inc., Upper Saddle River, NJ.
Medial Prefrontal Cortex
(mPFC) Changes
• Child abuse victims show impaired functioning:
• Failure to extinguish fear conditioning
• Decreased activity in mPFC correlates with
emotional stimuli interfering with simple cognitive
tasks
• Problem solving
• Future planning
• Emotional behavioral control
• Inhibition of stress response
Tost (2012)
Cognitive Function of
Maltreated Children
Multiple studies document impaired functioning
•
•
•
•
Decreased intellectual measurement
Verbal deficiencies
Lower reading ability
Deficits in attention, abstract reasoning and
executive functioning
• Higher rates of impulsivity
Important to determine specific deficits to
design effective interventions
Intervention Addresses Child
Maltreatment Psychopathology
Psychopathology
results from exposure
that depends on:
Duration
Severity
Age-of-onset
Gender*
Genetics*
Social supports and
evidence-based
interventions
promote recovery
from effects of
maltreatment
(*specific needs)
Males Less Resilient than Females
De Bellis, MD, Keshavan, MS (2003): Sex differences in
brain maturation in Maltreatment-Related Pediatric
Posttraumatic Stress Disorder.
Genetic Component Increases
Vulnerability in Some
Two genes have
been studied
• Monoamine
oxidase gene
(MAOA)
• Serotonin
transporter gene
(5-HTT)
Children
homozygous for
short allele of either
gene, were more
vulnerable to mental
health problems
• But only when
exposed to child
abuse /neglect
• Depression less
severe if have
social support
Specific Interventions Offer a
Positive Outcome
Even for those children with a genetic
predisposition to be severely affected if
abused, social supports were able to
ameliorate the PTSD and depression
Two
studies:
• McGloin, Widom (2001): Resilience
among abused and neglected children
grown up
• Kaufman (2004): Social supports and
serotonin transporter gene moderate
depression in maltreated children
Questions?
Kaufman
2004
“We believe the life course
trajectory of maltreated children
can be improved through
ongoing research efforts that
span from neurobiology to social
policy, identifying mechanisms
responsible for the etiology of
depression and other stressrelated psychiatric disorders and
systematically testing
interventions to improve the
system of care for these
children.”
References
• Crozier, J., E. Van Voorhees, et al. (2011). Effects of Abuse
and Neglect on Brain Development. Child Abuse and
Neglect: Diagnosis, Treatment, and Evidence. C. Jenny. St.
Louis, Elsevier/Saunders: 516-525.
• De Bellis, M. D., M. S. Keshavan, et al. (1999). "A.E.
Bennett Research Award. Developmental traumatology. Part
II: Brain development." Biol Psychiatry 45(10): 1271-1284.
• De Bellis, M. (2001): “Developmental traumatology: the
psychobiological development of maltreated children and its
implications for research, treatment, and policy.“
Development and Psychopathology 13: 537-561.
• De Bellis, M. D. and M. S. Keshavan (2003). "Sex
differences in brain maturation in maltreatmentrelated pediatric posttraumatic stress disorder."
Neurosci Biobehav Rev 27(1-2): 103-117.
• Kaufman, J., B. Z. Yang, et al. (2004). "Social
supports and serotonin transporter gene moderate
depression in maltreated children." Proc Natl Acad
Sci U S A 101(49): 17316-17321.
• McGloin, J. M. and C. S. Widom (2001). "Resilience
among abused and neglected children grown up." Dev
Psychopathol 13(4): 1021-1038.
• Permissions for Use of Illustrations
• Slide 7: Heulens, I. and F. Kooy (2011). "Fragile X
syndrome: from gene discovery to therapy." Front Biosci
16: 1211-1232. DOI: 3785 [pii]
• Slice 8: Sternberg, E. M. (2006). "Neural regulation of
innate immunity: a coordinated nonspecific host
response to pathogens." Nat Rev Immunol 6(4): 318-328.
• Slide 15: Morris, Charles G., Psychology: An
Introduction, 8th Edition, © 1996. Reprinted by
permission of Pearson Education, Inc., Upper Saddle
River, NJ.
• Slide 16: Tost, H. and A. Meyer-Lindenberg (2010). "I
fear for you: a role for serotonin in moral behavior." Proc
Natl Acad Sci U S A 107(40): 17071-17072.