Psych 311 - Psychophysical Development

OUTLINES

Chapter 4

Origin and Function of Embryonic Behavior

Rev. 1/19/03

 

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I.              Introduction

A.            Werboff and Gottlieb (1965)

1.             Behavioral teratology

2.             Adverse behavior

II.            Drugs

A.            Cross placenta by passive diffusion

B.            Levels greater in embryo due to immaturity of liver

C.            Covariants:

1.             Alcohol and cigarette use

2.             Cocaine abuse and reduction of food intake

3.             Obstetrical care and drug use

D.            Brazelton (1961)

1.             Infant displaying abnormal behaviors

2.             Demoralized mother to depression and ineffectual interaction

E.             Animal Subjects

1.             Allow control of drug exposure

2.             Cross-fostering

3.             Elimination of covariants

F.             Problems

1.             Selection of species

a.             Space

b.             Budget

2.             Mode of drug administration

3.             Dosage

III.           Alcohol

A.            Report of Lemoine, Harousseau, Bortegru and Menuet (1968)

1.             Describes similarities in growth retardation, facial features, and psychomotor disturbances among group of 127 children of alcoholic mothers.

2.             Similarities so marked that authors could diagnose maternal alcoholism by examining children.

B.            Jones, Smith, Ulleland, and Streissguth

1.             Reported a number of abnormalities of eleven offspring of alcoholic mothers ranging in ages of newborns to 48 months.

2.             Called FAS (Fetal Alcohol Syndrome) three categories.

a.             Growth retardation, dysmorphic characteristics, and Central Nervous System abnormalities.

b.             Growth retardation evidenced by low birth rate.

c.             Major dysmorphic features are craniofacial, low nasal bridge, drooping eyelids, epicanthic folds and thin upper lip

d.             Other abnormalities include hip dislocation and inability to extend elbow.

3.             CNS problems due to FAS include: microcephaly, seizures, hyperactivity, attentional deficits and learning/performance problems.

a.             IQ scores ranged 50-83

4.             To be diagnosed with FAS one must show symptoms of each of the 3 categories – those who do not meet that criteria have FAE (Fetal Alcohol Effects) which is more prevalent than FAS.

C.            Streissguth, Herman, and Smith (1978)

1.             20 offspring of alcoholic mothers (offspring-9 months to 20 years) base on the child’s disabilities

2.             Children given IQ tests and their caretakers were interviewed

3.             Scores ranged from 15-105 with an average of 65 (retardation)

D.            Shaywitz, Cohen, and Shaywitz (1980)

1.             Found that low IQ scores are not requisite for behavioral learning problems.

2.             Studied 15 children that had been referred to learning disorder clinic.

a.             All 15 displayed morphological anomalies associated with FAS.

b.             All exhibited failure in school environment.

c.             IQ scores ranged 80-113 with an average of 98.3.

E.             Findings

1.             Data shows that children of alcoholic mothers are at risk for a variety of physiological and behavioral abnormalities.

2.             Does only chronic exposure to alcohol produce FAS?

a.             Most women who drink while pregnant are not alcoholics.

3.             Study on 400 children where pregnant women kept records of alcohol consumption beginning 5th month, then given IQ tests when 4 years 3 months old.

a.             Found covariates, i.e. smoking, antibiotic exposure, race, etc. that related to test performance.

b.             Use of 1.5 ounces of alcohol (3 drinks) is associated with an average IQ decrement of 5 points (approximately).

F.             Streissgath, Sampson, and Barr (1989)

1.             Study on 1500 pregnant women regarding their alcohol, caffeine, cigarette and other drug use.

a.             Characterized as exhibiting light to moderate levels of alcohol consumption.

b.             Offspring assessed on days 1, 2, 8 and at 18 months, 4 and 7 years.  (See table 4.1) page 93.

c.             Even low to moderate alcohol consumption leads to behavior problems in children – so not only children of alcoholic mothers are affected.

G.            Abstinence

1.             Does abstinence for part or all of pregnancy prevent FAS?

a.             The answer is no.

b.             5 alcoholic women were sober between weeks 5 and 12 of gestation.

c.             8 women started as late as 22-25 weeks.

1)             Size at birth of offspring of later ‘sober group’ was depressed.

2)             Early ‘sober group’ did not have same effect.

3)             Both groups of offspring displayed abnormal patterns of brain electrical activity.

2.             Little, Streissguth, Barr and Herman repeated abstinence through the whole pregnancy did not prevent lowered birth weight.

a.             Shows that chronic prefertilization exposure to high levels of alcohol produce long term, maybe permanent effects on reproductive outcome.

b.             Autti-Ramo and Granstrom found a relation between degree of impairment and duration of heavy maternal alcohol consumption if not beyond first trimester – development was normal.

3.             Effects associated with alcohol exposure with humans have been produced experimentally in humans.

a.             Resemblance is striking.

H.            Prenatal alcohol exposure in humans found similar to experiments with animals, including primates with comparable dosages.

1.             Sulik, Johnston, and Webb (1981)

a.             Inject pregnant mice with low alcohol dosage twice

1)             Day 7 and 19 of gestation

2)             Resembled children with FAS at birth

3)             Concluded alcohol has a major effect on mice at equivalent to third month of human gestation

4)             Many women not aware of pregnancy at third month

5)             Therefore binge drinking could be as detrimental as heavy drinking during pregnancy

2.             Rockwood and Reilly (1986)

a.             Report rats prenatally exposed to alcohol exert less pressure on nipple when suckling, spend less time suckling, and display altered suckling pattern to non exposed rats

b.             Alcohol exposed rats take longer to acquire a response that brings them to the mother

c.             Take longer to commence suckling

I.              Sensorimotor maturation

1.             Molina, Hoffman, and Spear (1987)

a.             Prenatally alcohol exposed rats retarded on three endices

1)             Delay returning to a prone position from supine position

2)             Delay in auditory maturation

3)             Delay in horizontal screen test

b.             Prenatal alcohol exposure led to increased activity levels

c.             Required more trials to master passive-avoidance task

d.             Deficits in reversal learning and spontaneous alternation

2.             Gianoulakis (1990) Morris Swim Maze

a.             Rat must learn location of submerged platform

b.             Then must lift itself from the water

c.             Alcohol exposed rats displayed longer latencies to perform

d.             Also swam longer distances to locate platform

e.             Rats searched for platform when removed in places it had not been located

J.             Development of Sexually Dimorphic Behavior

1.             McGivern, Clancy, Hill and Noble (1984)

a.             Examined saccharin preferences and maze learning

1)             Females normally consume more saccharin than Males

2)             Males normally require fewer trials in a maze than Females

b.             Rats exposed to alcohol were sexually dimorphic

1)             Males ingested increased saccharin, Females better at mazes

2)             Also increased play behavior in Females, usually more common in males

3)             Prenatal alcohol exposure reverses typical male-female differences

4)             Also decreased males mounting receptive females

2.             McGivern, Raum, Salido, and Redel (1988)

a.             Suggest alcohol alters early hormonal milieu

1)             Assess testosterone levels in alcohol exposed and control rats

2)             Normal embryos increase testosterone, day 18

3)             Alcohol exposed embryos do not

K.            Alcohol alters brain development prenatally

1.             18 day old mouse embryos given alcohol between days 11-17 experience decrease in cells/gram of cerebrum and cerebral protein

2.             Alcohol decreases ability of cerebral cells to grow back

3.             Disrupts cellular organization of hippocampus

4.             Sexually dimorphic nucleus of preoptic area smaller

L.             Utero alcohol exposure alters morphological and behavioral development

1.             Hoyseth and Jones (1989)

a.             What does Alcohol do to the embryo?

1)             Interferes with placental transfers of nutrients

a)             Leads to impairment of growth and morphological deformations

2)             Produce abnormal muscle tissue; inhibits cellular migration

3)             Oxygen depravation leads to teratogenic effects on behavior

4)             Increase embryonic prostaglandin level leads to decreased rate of cellular division

5)             Effects hypothalamic-pituitary-adrenal axis

a)             Altered levels of adrenocorticotropic and growth hormone

b)            Disrupts release of anti-diuretic hormone

2.             Smotherman, Woodruff, Robinson, and Del Real (1986)

a.             Rat fetuses of mothers given alcohol exhibited 51% less spontaneous activity than controls

3.             Little et al. (1980)

a.             Abstinence did NOT prevent decreased birth weight

b.             Produces long term effects on reproduction

IV.           Cocaine

A.            The effects of cocaine on a developing organism.

1.             No longitudinal studies of the behavioral development of prenatally cocaine exposed children.

2.             Cocaine crosses the placenta.

a.             Less than a minute after maternal administration it can be detected in embryonic serum.

b.             The drug and its metabolite benzoylecgonine are found in the embryonic circulatory system and brain tissue at levels related to maternal dosage.

3.             Effects of cocaine on pregnancy reported by Acker, Sachs, Tracey and Wise.

a.             Abruptio placentae occurred in two patients after using cocaine.

1)             One neonate was stillborn

2)             The other was severely depressed

4.             Bingol reported some skull defects and unspecified major congenital malfunctions.

5.             MacGregor studied women who used cocaine during pregnancy along with a control group.

a.             The study population had a higher incidence of pre-term delivery, lower birth rate and were small for their gestational age.

6.             Chasnoff, Burns, Schnall and Burns administered the Brazelton Neonatal Behavioral Assessment Scale (NBAS) to three day old infants.

a.             Infants born to cocaine using mothers scored higher on tremulousness, irritability and state lability than the controls.

7.             Cohen, Anday and Leitehr reported hyperreactivity of cocaine exposed infants to sensory stimulation more than a week after birth.

8.             Neuspiel, Hamel, Hochberg, Greene and Campbell concluded the greatest risk was social environment.

9.             Doberczak, Shanzy, Sonie and Kandall recorded the EEG’s of 38 neonates exposed to cocaine during embryonic development.

a.             During the first week 17 children exhibited abnormalities characterized by cerebral irritation.

B.            The administration of cocaine to pregnant animals affects pregnancy outcome

C.            Data from Nonhumans

1.             Fantel and MacPhail

a.             reported decreased weights of cocaine exposed rat and mouse embryos in comparison to non-exposed embryos.

b.             non-exposed mothers were fed food in amount consumed by cocaine treated adults (pair-fed control group)

c.             maternal drug treatment led to elevated rates of uterine resorption

2.             Church, Dintcheff, and Gossner

a.             abruptio placentae

3.             Machalils, Gautae, and Mann

a.             found skeletal defects

b.             eye defects

4.             Woods, Plessinger, and Clark on prenatal cocaine

a.             decrease in uterine blood flow – reducing oxygen flow to the fetus (Hypoxia may be the cause of some abnormalities)

D.            Affects on different life functions and development

1.             Metabolics

a.             Don-Edwards et al, exposed rats on days 8- 22 via stomach intubation – dosage did not affect brain/body size

b.             of 45 brain structures, 2 cortical and 14 subcortical had a decrease in metabolic activities

c.             postnatal cocaine exposure on days 1-10 had no affect on males and increased metabolism in females

E.             Sleep Patterns

1.             Burchfield et al attached electrodes to fetal sheep (monitoring of electrical activities of cortex, eye movements, and neck activity)

a.             after intravenous infusion of cocaine the % of REM time declined significantly

b.             REM is hypothesized to foster cerebral maturation

F.             Sexual Differentiation (Males)

1.             Male rats born of mothers exposed to cocaine days 15- 20 of gestation exhibit less scent marking on days 60 and 80 of life

a.             deficits in copulatory behavior

1)             took almost 5 times as long to mount a sexually receptive female as did controls

2)             exposed subjects ejaculated after fewer intromissions

G.            Cocaine –exposed rats vs. pair-fed controls

1.             Spear et al. found that cocaine does not have an effect on body weight at birth and weaning

H.            Electric shock

1.             Painful stimulus administered to exposed and unexposed rats

a.             2 responses are normal

1)             wall climbing

2)             movement

b.             tests given in cage on days 8, 10, 12, 14, 16

c.             cocaine rats exhibited more movement and less wall climbing

1)             cocaine rats did not differ in overall sensitivity to electric shock

I.              Hutchings et al

1.             Cocaine’s affect on locomotor activity

a.             on days 20 and 23, cocaine rats were more active than pair-fed control groups

V.            Diethylstilbestrol

A.            Diethylstilbestrol (DES) is a compound with estrogen properties – prescribed to suppress lactation, alleviate menopausal symptoms, treat severe pain, prevent conception, and control carcinoma of the prostate and breast in humans and to promote weight gain in cattle.

B.            DES was banned in the U.S. because of its carcinogenic action on female offspring.

C.            Herbst, Ulfelder, Poskanzer (1971)

1.             First to show the relation between prenatal DES exposure and adenocarcinoma of the vagina.

2.             Exposure to DES is also responsible for vaginal adenosis, menstrual irregularities, hirsutism, pregnancy problems, increased risk of premature delivery and prenatal death.

D.            Behavioral Abnormalities have also been reported due to DES exposure, by acting on the embryonic brain.

E.             Vessay, Fairweather, Norman- Smith, Buckley

1.             DES was given to mothers being treated for toxemia during 1st pregnancy.

2.             Treatment commenced in the 12th week.

3.             Average amount taken was 11.5 grams.

4.             The children were between 25 and 30 when investigation resumed.

a.             There was no difference between the exposed and unexposed men.

b.             Although, the DES exposed (14%) exhibited psychiatric disorders including depression, anxiety, and anorexia.

5.             Vessay, Vessay, Fairweather, Norman- Smith, and Buckley concluded that utero exposure to DES adversely affects psychological well-being.

F.             Hines, Shipley

1.             Gestational exposure to DES affects cerebral lateralization, which is greater in men then women.

2.             Tested were 25 daughters (14-29 yrs old) of mother treated with DES.

3.             The exposed and unexposed differed in dichotic learning the exposed were much more able to identify sounds entering the right ear (left hemisphere).

G.            Ehrnardt, Meyer- Bahlburg

1.             Assessed the sexuality of women exposed to DES.

2.             30 women (ages from 17-30) all whom had vaginal adenosis, were compared to non- hormone exposed sample.

3.             The control women had a history of abnormal papanicolaow smears.

4.             The DES exposed women did not differ from controls on the age os attainment of various indices of psychosexual development- however, a difference did emerge on measure of sexual orientation.

5.             Exposed women exhibited higher levels of bisexual or homosexual responsiveness on various items relating to masturbation fantasies, sexual attractions and sexual relations/ sexual responsiveness.

6.             DES women reported low sex drives and low frequency of sexual thoughts.

H.            Masculinization of sexual behavior can be produced by early exposed to estrogen as well as androgen.

1.             It was suggested that estrogen might be the active agent in the masculinization process.

2.             DES may masculinize and/ or defeminize human females.

VI.           Phenobarbital

A.            Barbiturates, in particular Phenobarbital, have been prescribed to pregnant women to

1.             Treat insomnia, morning sickness and epileptic seizures

2.             Reduce stress associated with labor and delivery

3.             Reduce serum levels of bilirubin in the embryo

B.            Adversive consequences of prenatal barbiturate exposure in humans

1.             Congenital heart disease and abnormalities are reported 2-3 times greater in off spring of epileptics who took barbiturates

2.             Bazelton (1961)

a.             High-dose barbiturates (150 mg) exposed group took longer to exhibit responsive feedings than low-dose group

3.             Exposure just prior to delivery appears to reduce the amount of time infants spend looking at visual stimuli

a.             Causes abnormalities of brain electrical activities

C.            Adversive consequences seen in non-human subjects

1.             Barbiturates produce alterations of behavior and nervous system

2.             Prenatal exposure retards acquisition of active and passive avoidance responding and reduces operant responding on fixed ratio schedule of reinforcement

3.             Leads to reproductive dysfunction

a.             Gupta and Yaffe (1981)

1)             Administered Phenobarbital to pregnant rats

a)             Measured sexual maturation of female offspring

2)             Speculated that Phenobarbital may act on the hypothalamus to inhibit release of gonadotrophins

b.             Causes a delay in testicular descent and infertility

1)             Testosterone deficit probably accounts for the significant diminution of male, but not female, sexual behavior following Phenobarbital treatment

D.            Data from humans and animals demonstrate that early exposure to barbiturates leads to wide-ranging alterations in behavior

1.             Also influences development of CNS morphology and biochemistry

2.             2 areas of brain are affected

a.             Hippocampus and cerebellum

1)             Exposure causes reduction in number of cerebellar Purkinje cells and hippocamppal pyramidal cells which normally develop prenatally

3.             Decreased hypothalamic levels of norepinephrine and dopamine as well as altercations in the dopamine receptor binding, are found in rats exposed in utero

VII.          X-irradition

A.            Affects motor activity, emotionality/arousal, and conditioning/learning

B.            Otake & Schull

a.             Found period of maximum susceptibility was between weeks 8 and 15 post-conception

C.            Motor Activity

1.             Furchtgott & Echols

a.             27 day old rats on metal rods

b.             Increased distance between rods

c.             More radiation they were exposed to the shorter the maximum distance between rods

2.             Werboff & Goodmen (1961)

a.             Found that prenatually irradiated rats have less motor control strength, less ability to climb up inverted planes, and they are slower in developing upright posture

3.             Sikov, Resta, Lofstrom, & Meyer (1962)

a.             Found hypersensitivity to stimuli, and also a major defect in locomotion activity in rats

b.             In male rats at time of puberty they developed priapism; chronic penile tumescence

D.            Emotionality/Arousal

1.             Rats show higher levels of active and passive behavior.  They also don’t want to leave their home settings.

2.             Show a decline in open-field activity

E.             Conditioning/ Learning

1.             Commit more errors in complex maze tests if exposed

F.             Exposure

1.             Ader & Deltchman (1972)

a.             Irradiated mothers spend less time with their young.  Their offspring are also less emotional, weigh less, and are more sensitive to further irradiation

2.             Rakic (1986)

a.             Suggested that irradiation also interferes with neuronal migration

VIII.        Rubella

A.            Viral disease that is transmitted from the female to the embryo by way of the placenta

1. Relations between maternal rubella and congenital heart disease

2.             Congenital defects more likely when disease is contracted with in the first two months of pregnancy

B.            Rubella virus produces malformations directly by causing cell death and inhibiting mitosis

1.             Causes vascular damage

2.             Associated with mental retardation

3.             Rubella virus is a behavioral teratogen

C.            Post epidemic study by Desmond and co-workers

1.             Examine 100 rubella children

2.             Children showed neurologically abnormalities

a.             Motor deficits

b.             Autistic

D.            Chess and associates studied 243 children enrolled in the Rubella Birth Defect Evaluation Project

1.             Children were 2.5-4.0 years of age

a.             Approximately 80 percent had rubella associated physical deficits such as visual auditory and etc.

2.             The greater the number of deficits the higher the probity that child would suffer a psychiatric disorder

a.             Mood problems

b.             Sleep and eating problems

c.             Odd habits and rituals

d.             High rate of autism

3.             Intellectual development assessed with standard intelligence tests

a.             2-3 percent of children in general population as compared to 23 percent or rubella children classified as retarded

b.             Children’s cognitive abilities go down as the number of physical defects rise

4.             Some children recovered from autism others were later diagnosed so Chess concluded that autism runs its course similar to that of a viral infection such as rubella

a.             Recovery chronically improvement worsening and delayed effect can all occur