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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

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Exposure to Teratogenic Agents as a Risk Factor for Psychopathology

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Exposure to teratogenic agents as a risk factor for psychopathology

Exposure to

Teratogenic Agents

as a Risk Factor for Psychopathology

Child and Adolescent Psychopathology


Exposure to teratogenic agents as a risk factor for 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


  • Exposure to teratogenic agents as a risk factor for psychopathology

    (Cont’d)

    • Environmental risk factors can moderate teratological effects

      • Family placement (biological, foster, adoptive)

      • SES

      • Global intelligence


    Exposure to teratogenic agents as a risk factor for psychopathology

    Fetal Alcohol Spectrum Disorders (FASD)

    • 3 presenting symptoms:

      • Pre- and postnatal growth deficiency

      • Dysmorphicfacial features

      • CNS dysfunction

    • incidence 1/1,000 per live births for FAS

    • incidence 9.1/1,000 live births for dysmorphic

    • and non-dysmorphic cases


    Exposure to teratogenic agents as a risk factor for psychopathology

    • Symptoms

    • Of FASD:

    • Stereotypies

    • Sleeping problems

    • Tics

    • Hand/body rocking

    • Peer-relationship

    • difficulties

    • Phobias

    • Depression

    • Bipolar DO

    *Psychiatric symptoms in children do not dissipate with time.


    Exposure to teratogenic agents as a risk factor for psychopathology

    • Disruptive behavior disorders (associated with FASD):

    • ADHD, ODD, CD

    • Attention deficits are useful markers of FASD

    • 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


    Exposure to teratogenic agents as a risk factor for psychopathology

    • 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


    Exposure to teratogenic agents as a risk factor for psychopathology

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

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

    FASD + gender + maternal depression

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

    • Girls  depression

    • 2) Maternal depression 

    • depression


    Exposure to teratogenic agents as a risk factor for psychopathology

    • Social skills deficits (after controlling for IQ)

    • 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)


    Exposure to teratogenic agents as a risk factor for psychopathology

    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


    Exposure to teratogenic agents as a risk factor for psychopathology

    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


  • Exposure to teratogenic agents as a risk factor for psychopathology

    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)


    Exposure to teratogenic agents as a risk factor for psychopathology

    Clinical Implications

    • Take careful prenatal exposure histories

    • Different response pattern to treatments

    • Stable, nurturing home buffers effects of alcohol

    • exposure


    Exposure to teratogenic agents as a risk factor for psychopathology

    Brain Injury as a Risk Factor for Psychopathology

    Symptoms of closed head injuries:

    • Cognitive:

      • confusion, poor concentration, inability to follow directions or answer questions, amnesia, loss of consciousness

    • Medical:

      • headaches, nausea, vomiting

    • Sensory:

      • dizziness, poor coordination or loss of balance, alterations in vision or hearing (seeing stars, ringing ears

    • Psychological:

      • irritability, changes in personality, emotions inappropriate for context


    Exposure to teratogenic agents as a risk factor for psychopathology

    Assessment of closed head injuries

    • Past:

    • Sideline assessments of concussive symptoms

    • Present :

    • Comparison with baseline administration of standardized neuropsychological tests


    Exposure to teratogenic agents as a risk factor for psychopathology

    1) Nontraumaticbrain injuries

    Causes:

    Susceptibility

    Low birth weight

    Prematurity

    Prenatal teratologicalexposure

    Exposure to maternal cortisol

    Restricted blood flow through umbilical artery

    Nutritional differences

    Insufficient oxygen supply

    • Males

    • ADHD (and greater severity)

    • Low SES

    • Poor parental supervision

    • (ADHD—> poor supervision—> brain injury

    • injury)

    Equifinality and multifinality of outcomes

    *Archives of Disease in Childhood, 2001


    Exposure to teratogenic agents as a risk factor for psychopathology

    2) Traumatic brain injury (TBI)

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

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

    a. Small hemorrhages on overall 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


    Exposure to teratogenic agents as a risk factor for psychopathology

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

    • Mild injuries accumulated over time can be dangerous

    • Secondary injuries:

    a. Edema--swelling

    b. global tissue damage


    Exposure to teratogenic agents as a risk factor for psychopathology

    Hypoxia--reduction in oxygen supply

    • Toxic accumulation of calcium in cells

    • Apoptosis--programming death of neighboring cells

    • Accumulation of cell loss over weeks produces behavioral

    • deficits

    • Common complication of preterm infants

    • Factors related to hypoxia: developmental maturation of

    • neural tissue, duration and degree of hypoxic exposure, degree of neuroprotective factors

    • Sequence following hypoxia: cognition/behavior impairments, motor incoordination

    • Ischemia (reduced blood supply to cell) potentiates hypoxia effects

    • ADHD risk even in absence of marked neurological dysfunction


    Exposure to teratogenic agents as a risk factor for psychopathology

    Role of genes in brain injury

    E4 allele confers vulnerability for development of Alzheimer’s and TBI for adults but protection for children

    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


    Exposure to teratogenic agents as a risk factor for psychopathology

    Fin


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