Transcript Slide 1

Exposure to
Teratogenic Agents
as a Risk Factor for
Psychopathology
Child and Adolescent
Psychopathology
General Points

Exposure might be inevitable because of
pharmacological intervention
• e.g., seizure, depression

Exposure can occur prior to knowledge of
pregnancy

Behavioral teratogens can cause changes in
function
• e.g., cognitive, affective, sensorimotor, social
(Cont’d)
 Environmental risk factors can moderate
teratological effects
• Family placement (biological, foster, adoptive)
• SES
• Global intelligence
Fetal Alcohol Spectrum Disorders (FASD)
3 presenting symptoms:
1) Pre- and postnatal growth deficiency
2) Dysmorphic facial features
3) CNS dysfunction
 incidence 1/1,000 per live births for FAS
 incidence 9.1/1,000 live births for dysmorphic
and non-dysmorphic cases
Symptoms
Of FASD:
Stereotypies
Sleeping problems
Tics
Hand/body rocking
Peer-relationship
difficulties
o Phobias
o Depression
o Bipolar DO
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*Psychiatric symptoms in children do not dissipate with time.
o Disruptive behavior disorders (associated with FASD):
• ADHD, ODD, CD
• Attention deficits are useful
markers of FASD
o Exposure amount and
home placement moderate
the
relationship between alcohol
exposure and delinquency
• biological and foster homes
=>  in delinquency
• adoptive homes
=>  in delinquency
*Possible mediational model:
FASD  attentional/impulse control problems 
conduct problems
o Mood
Disorders (associated with FASD):
 Mediational model #1 (O’Conner, 2001):
FASD  negative infant affect  depressive features at age 6
 Mediational model #2 (O’Conner & Paley, 2006):
FASD  quality of mother-child interaction 
depression
o
Mood Disorders (associated with FASD): (Cont’d)
 Moderational
model
(O’Conner & Kasari, 2000):
FASD + gender + maternal depression
+ (FASD × gender) + (FASD × maternal depression)  depression
1) Girls   depression
2) Maternal depression 
 depression
o
Social skills deficits (after controlling for IQ)
o
Many potential pathways suggest equifinality:
 Factors
that affect pathway selection:
 Timing (pregnancy stage, dosage,
pattern of exposure, maternal
characteristics, fetal genetic factors)
 Pattern of infant withdrawal
(not discussed in book)
Nicotine Exposure
 Conduct problems (controlling for genetic factors
and parental antisocial behavior)
 Antisocial behaviors
 ADHD (controlling for SES, parental IQ, parental ADHD)
 Moderational model:
DA transporter gene (DTG) + exposure + (DTG × exposure)
ADHD/ODD
 Higher rates of substance abuse and depression
Stimulant drugs
 Increased aggression in cocaine-exposed children
 Gender and comorbid alcohol exposure moderate their
relation
 Other risk factors more predictive of psychopathology than
cocaine exposure:
•
caregiver’s recent drug use
•
caregiver’s level of mental functioning
•
caregiver’s depressive symptoms
 Many potential pathways suggest equifinality:
•
Factors that affect pathway selection -- gender and gestational age
•
Disrupted balance between dopaminergically mediated and noradrenergically
mediated arousal-regulating systems  hyperarousal
Methylmercury and Lead
 Neurobehavioral deficits
 Prenatal and postnatal exposure (true for all drug
exposure)
 Delinquency and antisocial behavior (controlling
for birth weight, parental IQ, quality of home
environment, SES)
Clinical Implications

Take careful prenatal exposure histories

Different response pattern to treatments

Stable, nurturing home buffers effects of alcohol
exposure
 Symptoms
of closed head injuries:
Assessment of closed head injuries
Past:
o Sideline assessments of
concussive symptoms
Present :
o Comparison with baseline
administration of standardized
neuropsychological tests
1) Nontraumatic brain injuries
Causes:
Low birth weight
Prematurity
Prenatal teratological exposure
Exposure to maternal cortisol
Restricted blood flow through
umbilical artery
Nutritional differences
Insufficient oxygen supply
Equifinality and
multifinality of outcomes
Susceptibility
• Males
• ADHD (and greater severity)
• Low SES
• Poor parental supervision
(ADHD—> poor supervision—> brain
injury
injury)
*Archives of Disease in
Childhood, 2001
2) Traumatic brain injury (TBI)
① Focal--translational force
② Diffuse--rotational forces
applied along brain’s linear
applied in angular
axis
movement around brain’s
a. Small hemorrhages on overall
center of gravity
surface of the brain
b. Coup/contrecoup-rebound effect
on opposite side
a. Head strikes against broad
object, diffusing force across
the surface of the skull
b. Shearing strain on brain,
tearing axonal tissue
c. Most common form of
head injury, producing
concussions
③ Head injuries are classified as
mild, moderate, or severe using
Glasgow Coma Scale
③ Mild injuries accumulated over
time can be dangerous
⑤ Secondary injuries:
a. Edema--swelling
b. global tissue damage
Hypoxia--reduction in oxygen supply
o Toxic accumulation of calcium in cells
o Apoptosis--programming death of neighboring cells
o Accumulation of cell loss over weeks produces behavioral
deficits
o Common complication of preterm infants
o Factors related to hypoxia: developmental maturation of
neural tissue, duration and degree of hypoxic exposure, degree
of neuroprotective factors
o Sequence following hypoxia: cognition/behavior impairments,
motor incoordination
o Ischemia (reduced blood supply to cell) potentiates hypoxia
effects
o ADHD risk even in absence of marked neurological
dysfunction
Role of genes in brain injury
1) E4 allele confers vulnerability for development of
Alzheimer’s and TBI for adults but protection for
children
2) Mediational model of schizophrenia:
Genetic heightened sensitivity to hypoxic event 
hypoxia  schizophrenia
3) ADHD and schizophrenia: vulnerability of
dopaminergic system to hypoxic insult
4) Female brains less vulnerable to ischemia/
hypoxia-induced damage
5) Moderating variables: exacerbation of preexisting
pathology, reaction of child/family to loss of
function, PTSD formation
6) High family functioning protects against the effects of
brain injury (moderational model)
7) Ritalin less effective for hypoxia/TBI-induced ADHD
Fin