University of Saskatchewan Department of Psychology

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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.

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Introduction

• Alcohol
• Most commonly used human prenatal teratogen
• Research to date
• prospective retrospective studies
• animal models
• neuroanatomical studies

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Introduction

• Fetal Alcohol Syndrome - FAS
• History of maternal alcoholism during pregnancy
• Central nervous system deficits
• Facial dysmorphology
• Pre- and post-natal growth retardation

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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

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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

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Introduction

• Theoretical Questions
• What 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.

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Method

• Design
• Childhood dx of FAS
• Childhood dx of MPKUS
• Chronological age and IQ matched Controls

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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

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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

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Measures

• Mirskys 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.

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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

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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.

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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

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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.

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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

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Exploratory Question I

• Attention
• How 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.

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Results

• Attention
• Focus ? No differences
• Sustain ? MPKUS more omission errors on auditory
  CPT test
• Shift ? Controls more set losses on WCST
• Encode ? no differences

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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.

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Results

• Verbal Memory
• MPKUS ? poorer recognition skill

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Exploratory Question III

• Visual Memory
• How 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.

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Results

• Visual Memory
• No differences

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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.

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Recommendations

• FAS
• Current 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.

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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.

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FAS MPKUS

• Theoretical Question
• Are the relative effects of prenatal exposure to
  alcohol or phenylalanine different.

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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

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Exploratory Question I

• Attention
• Do 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.

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Results

• Attention
• Controls ? more correct responses
• FAS ? more omission and commission errors than
  MPKUS Controls
• MPKUS ? more omission and commission errors than
  Controls

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Exploratory Question II

• Memory
• Do 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.

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Results

• Memory
• Controls ? immediate delayed recall superior to
  FAS MPKUS
• FAS ? more intrusion errors than MPKUS Controls
• FAS ? lost information over delay

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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.

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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.

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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