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

 Environmental risk factors can moderate teratological effects Family placement (biological, foster, adoptive) SES Global intelligence (Cont’d)

3 presenting symptoms: 1)Pre- and postnatal growth deficiency 2) Dysmorphic facial features 3) 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)

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.

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

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

 Moderational model ( O’Conner & Kasari, 2000): FASD + gender + maternal depression + (FASD × gender) + (FASD × maternal depression)  ddepression 1)Girls    depression 2) Maternal depression    depression o Mood Disorders (associated with FASD): (Cont’d)

 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)

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

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

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

Take careful prenatal exposure histories Different response pattern to treatments Stable, nurturing home buffers effects of alcohol exposure Clinical Implications

 Symptoms of closed head injuries:

Present : oCoC omparison with baseline administration of standardized neuropsychological tests Assessment of closed head injuries Past : oSoS ideline assessments of concussive symptoms

Low birth weight Prematurity Prenatal teratological exposure Exposure to maternal cortisol Restricted blood flow through umbilical artery Nutritional differences Insufficient 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

a. Small hemorrhages on overall surface of the brain b. 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 skull b. Shearing strain on brain, tearing axonal tissue c. Most common form of head injury, producing concussions ② Diffuse--rotational forces applied in angular movement around brain’s center of gravity

③ Head injuries are classified as mild, moderate, or severe using Glasgow Coma Scale ③ Mild injuries accumulated over time can be dangerous a. Edema--swelling b. global tissue damage ⑤ Secondary injuries:

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 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

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) M ediational model of schizophrenia : Genetic heightened sensitivity to hypoxic event  hypoxia  s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

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