university of saskatchewan department of psychology an investigation of the long-term...
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University of Saskatchewan Department of Psychology
An Investigation of the Long-term
Neuropsychological Outcome of Prenatal Teratogenic Exposure : Fetal Alcohol Syndrome and Maternal PKU Syndrome.
Jo Nanson, Ph. D. and
Susan R. Brock, Ph. D.
Introduction
Alcohol Most commonly used human prenatal teratogen Research to date
prospective & retrospective studies animal models neuroanatomical studies
Introduction
Fetal Alcohol Syndrome - FAS History of maternal alcoholism during pregnancy Central nervous system deficits Facial dysmorphology Pre- and post-natal growth retardation
Introduction
Phenylalanine A large neutral amino acid in food PKU - autosomal, recessive metabolic disorder
affected individuals unable to metabolize phenylalanine resulting in build up in the bloodstream.
Fetal-maternal plasma gradient for phenylalanine exists across the placenta
Introduction
Maternal PKU Syndrome - MPKUS History of untreated maternal PKU during
pregnancy Effects on the development of young children have
been broadly described Clinical reports have documented CNS deficits,
microcephaly, intrauterine growth retardation, and congenital anomalies
Empirical data is lacking
Introduction
Theoretical QuestionsWhat is the long-term neuropsychological outcome
of prenatal teratogenic exposure in terms of memory and attention functioning.
Are there unique patterns of prenatal teratogenic exposure that are specific to individual teratogens.
Method
Design Childhood dx of FAS Childhood dx of MPKUS Chronological age and IQ matched Controls
Method
Participants - Prenatal Teratogen Groups 17 adults with FAS
9 male, 8 female 12 Native, 5 Caucasian
12 adults with MPKUS 5 male, 7 female 12 Caucasian
Method
Participants - Control Group 84 adults administered the WAIS-R 17 CA + IQ matches for FAS participants
10 male, 7 female 4 Native, 13 Caucasian
12 CA + IQ matches for MPKUS participants 5 male, 7 female 12 Caucasian
Measures
Mirsky’s four factor model of Attention Focus ability to select target information from an
array for enhanced processing. Sustain ability to maintain focus and alertness
over time. Shift ability to change attentive focus in a
flexible and adaptive manner. Encode ability to sequentially register, recall, and
mentally manipulate numeric information.
Measures
Memory Battery The WMS-R, RAVLT, and Rey Complex Figure
were selected based on their ability to broadly assess the following areas: Ability to learn Immediate & delayed verbal memory Recognition Immediate & delayed visual memory
FAS Hypothesis
Hypothesis I Based on the literature to date, it was expected that
adults with FAS would demonstrate poorer performance than the CA- plus IQ-matched Control group in terms of capacity to focus, sustain, shift, and encode attention as defined by Mirsky et al.'s model of attention.
Attention Results
Hypothesis I Focus FAS more commission errors Sustain FAS more commission errors, less
omission errors, and no differences in mean reaction time
Shift FAS less correct responses and less perseverative responses
Encode FAS poorer arithmetic scores
FAS Hypothesis
Hypothesis II Based on the literature to date, it was expected that
adults with FAS would demonstrate poorer performance than the CA- plus IQ-matched Control group in terms of verbal memory, including the ability to learn new information, and immediate, delayed, and recognition memory ability.
Memory Results
Hypothesis II FAS flatter learning curve FAS more difficulty with immediate & delayed
recall of word lists, & delayed recall of paragraphs & word pairs
FAS more intrusion errors
Exploratory Question I
AttentionHow do adults with MPKUS differ from a CA- plus
IQ-matched Control group in terms of capacity to focus, sustain, shift and encode attention as defined by Mirsky et al.'s model of attention.
Results
Attention Focus No differences Sustain MPKUS more omission errors on
auditory CPT test Shift Controls more set losses on WCST Encode no differences
Exploratory Question II
Verbal Memory How do adults with MPKUS differ from a CA- plus
IQ-matched Control group in terms of verbal memory, including ability to learn new information, immediate and delayed recall, and recognition memory ability.
Results
Verbal Memory MPKUS poorer recognition skill
Exploratory Question III
Visual MemoryHow do adults with FAS or MPKUS differ from a
CA- plus IQ-matched Control group in terms of visual memory, including immediate and delayed recall.
Results
Visual Memory No differences
Conclusions
FAS When CA and IQ-matched Controls are employed the
pattern of attention and verbal memory deficits seen in adults with FAS is similar to previous research documenting the pattern of deficits in children with FAS.
Adult individuals with FAS appear to have deficits in acquisition of new material, immediate and delayed recall of verbal material and deficits in response inhibition.
Recommendations
FASCurrent data suggests that the following may be helpful: Pharmacological interventions and cognitive strategies
designed to reduce impulsivity and increase reflectivity. Educational and vocational planning that incorporates a high
degree of structure and repetition and utilizes both verbal and nonverbal instruction and cueing.
Research paradigms that attempt to further elucidate the basis of the attention and memory deficits identified in individuals with FAS, at behavioral, psychosocial, neuroanatomical and neurochemical levels.
Conclusions
MPKUS It is difficult to draw firm conclusions regarding
the MPKUS data due to the small sample size, and the bimodal distribution of IQ in the sample.
Further research is needed utilizing a larger sample, and a battery of tests more sensitive to differences in ability at the low end of the IQ range.
FAS & MPKUS
Theoretical QuestionAre the relative effects of prenatal exposure to
alcohol or phenylalanine different.
Method
Participants FAS and MPKUS participants whose Full Scale IQ
were within 5 IQ points were paired resulting in 10 matches - unable to match on age
7 FAS and 1 MPKUS participant eliminated from further analyses
10 Control participants selected based on an IQ match within 5 points of one of the 10 prenatal teratogen pairs
Results - 10 triplets matched within 5 points on IQ
Exploratory Question I
AttentionDo adults with FAS differ significantly from adults
with MPKUS in terms of capacity to focus, sustain, shift and encode attention as defined by Mirsky et al.'s model of attention.
Results
Attention Controls more correct responses FAS more omission and commission errors
than MPKUS & Controls MPKUS more omission and commission errors
than Controls
Exploratory Question II
MemoryDo adults with FAS differ significantly from adults
with MPKUS in terms of verbal and visual memory, including the ability to learn new information, immediate and delayed recall, and recognition memory ability.
Results
Memory Controls immediate & delayed recall superior to
FAS & MPKUS FAS more intrusion errors than MPKUS &
Controls FAS lost information over delay
Conclusions
Randomized Block Analyses Failed to reveal some of the differences found in
the FAS paired analyses Groups differed in intrusion errors, immediate
recall of visual material, omission and commission errors, and recognition ability.
MPKUS appears more similar that different from their IQ matched controls.
General Conclusions
Attention & Memory FAS appear more affected in terms of memory &
attention relative to MPKUS & Controls. Lack of consistency with previous research in
terms of the pattern of attention and memory deficits identified is likely due to the use of IQ matched controls in the present study.
The large within group variance may have masked differences between the groups.
Recommendations
Future Research Replication of findings with larger samples and
more sensitive measures is needed Comparison of the attention & memory findings
with measures of social and emotional development