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Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology
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Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Jan 20, 2016

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Page 1: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Exposure to Teratogenic Agents

as a Risk Factor for Psychopathology

Child and Adolescent Psychopathology

Page 2: 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

Page 3: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Environmental risk factors can moderate teratological effects

• Family placement (biological, foster, adoptive)• SES• Global intelligence

(Cont’d)

Page 4: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

3 presenting symptoms:

1)Pre- and postnatal growth deficiency2)Dysmorphic facial features3)CNS dysfunction

incidence 9.1/1,000 live births for dysmorphic

and non-dysmorphic cases

incidence 1/1,000 per live births for FAS

Fetal Alcohol Spectrum Disorders (FASD)

Page 5: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Symptoms Of FASD:

o Stereotypies o Sleeping problems o Tics o Hand/body rocking o Peer-relationship difficulties o Phobias o Depression o Bipolar DO

*Psychiatric symptoms in children do not dissipate with time.

Page 6: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

• 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

o Disruptive behavior disorders (associated with FASD):

*Possible mediational model: FASD attentional/impulse control problems conduct problems

Page 7: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

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

Page 8: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Moderational model (O’Conner & Kasari, 2000):

FASD + gender + maternal depression + (FASD × gender) + (FASD × maternal depression)

depression

1)Girls depression

2) Maternal depression depression

o Mood Disorders (associated with FASD): (Cont’d)

Page 9: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Factors that affect pathway selection:

o Social skills deficits (after controlling for IQ)

o Many potential pathways suggest equifinality:

Pattern of infant withdrawal

(not discussed in book)

Timing (pregnancy stage, dosage, pattern of exposure, maternal characteristics, fetal genetic factors)

Page 10: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

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

Nicotine Exposure

Page 11: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

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

Stimulant drugs

Page 12: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

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)

Methylmercury and Lead

Page 13: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Take careful prenatal exposure histories

Different response pattern to treatments

Stable, nurturing home buffers effects of alcohol

exposure

Clinical Implications

Page 14: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

1)Cognitive: • confusion, poor concentration, inability to

follow directions or answer questions, amnesia, loss of consciousness

2)Medical: • headaches, nausea, vomiting

3)Sensory: • dizziness, poor coordination or loss of

balance, alterations in vision or hearing (seeing stars, ringing ears

4)Psychological: • irritability, changes in personality, emotions

inappropriate for context

Symptoms of closed head injuries:

Brain Injury as a Risk Factor for Psychopathology

Page 15: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Present : o Comparison with

baseline administration of standardized neuropsychological tests

Assessment of closed head injuries

Past: o Sideline

assessments of concussive symptoms

Page 16: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Low birth weightPrematurityPrenatal teratological exposureExposure to maternal cortisolRestricted blood flow through umbilical artery Nutritional differencesInsufficient oxygen supply

1) Nontraumatic brain injuries

Causes:

Equifinality and multifinality of outcomes

• Males• ADHD (and greater

severity)• Low SES• Poor parental

supervision(ADHD—> poor supervision—> brain

injury

injury)

Susceptibility

*Archives of Disease in Childhood, 2001

Page 17: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

a. Small hemorrhages on overall surface of the brainb. Coup/contrecoup-rebound effect on opposite side

① Focal--translational force applied along brain’s linear axis

2) Traumatic brain injury (TBI)

a. Head strikes against broad object, diffusing force across the surface of the skullb. Shearing strain on brain, tearing axonal tissuec. Most common form of head injury, producing concussions

② Diffuse--rotational forces applied in angular movement around brain’s center of gravity

Page 18: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

③ Head injuries are classified as mild, moderate, or severe using Glasgow Coma Scale

④ Mild injuries accumulated over time can be dangerous

a. Edema--swellingb. global tissue damage

⑤ Secondary injuries:

Page 19: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

oToxic accumulation of calcium in cellsoApoptosis--programming death of neighboring

cellsoAccumulation of cell loss over weeks produces

behavioral deficitsoCommon complication of preterm infants oFactors related to hypoxia: developmental

maturation of neural tissue, duration and degree of hypoxic

exposure, degree of neuroprotective factors

Hypoxia--reduction in oxygen supply

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

Page 20: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

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 insult4) Female brains less vulnerable to ischemia/

hypoxia-induced damage5) 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

Page 21: Exposure to Teratogenic Agents as a Risk Factor for Psychopathology Child and Adolescent Psychopathology.

Fin