Cognitive Effects in Adolescents Exposed Prenatally to Marihuana or Cigarettes

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Cognitive Effects in Adolescents Exposed
Prenatally to Marihuana or Cigarettes

• American Psychiatric Association
• New York, 2004

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• Prenatal Marihuana Exposure and Its Putative
  Impact Upon Executive Functioning in Offspring
• A 25 Year Prospective Study

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The Ottawa Prenatal Prospective Study
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Two General Areas

• General Cognition and Executive Function
• Visuoperception

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Summary of Cigarette Findings0-4 years of age

• Newborn - ? auditory responsiveness
  habituation ?tremors motoric
  reflexes
• 1 year - ? MDI (96 vrs 110) verbal cluster.
• 2 years - ? MDI (106 vrs 119) Reynell
  Expressive Comprehensive. Significance lost
  when confounds controlled.
• 3 years - ? GCI language after confounds
  controlled.
• 4 years - ? GCI language after confounds
  controlled

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Prenatal Marihuana Summary Up To
Preschool

• Course of pregnancy, fetal and postnatal growth
  and behavior are relatively unaffected during
  neonatal and toddler stages
• Starting at approximately 3 years of age
  converging findings suggest that overall IQ is
  not affected but abstract/visual reasoning
  subscales on IQ tests are negatively impacted as
  are facets of attention.
• Together, this suggests an impact on aspects of
  Executive Function - this will be elaborated in a
  moment.

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Effects of Prenatal Exposure to Marihuana
(and Cigarettes) on Cognitive Tasks in 9 to 12
Year-Old Offspring
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Differential Consequences of the Drugs

• General Intelligence versus Aspects of Executive
  Function

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Executive Functioning which is largely under the
control of Prefrontal LobesInvolves

• Planning for the future/decision making
• Self monitoring/error correction/flexibility/budge
  ting of time
• Working Memory- Integration of past and new
  information
• Control over dominant responses
• Attention allowing control of interference
• The Prefrontal lobes allow us to respond
  -not simply react

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Paradox of Executive System Assessment

• Trying to assess ability to set goals, plan
  organize behavior in pursuit of those goals, and
  flexibly solve problems in the context of an
  unstructured real world
• YET
• using a test situation in which
• highly structured tasks are presented in a highly
  controlled environment

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The evaluator and evaluation context can become
the prosthetic frontal lobes for the subject.
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Poor Executive Function

• A dysregulation of goal directed behaviour
• not attributable to a more basic deficit in
  perception, memory, or language comprehension
• Occurs across tasks varying in content surface
  characteristics
• Despite understanding goal of task, prefrontal
  dysfunction results in impaired performance
  (intrusions of task irrelevant behaviour,
  perseveration, lack of initiative etc.)

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Tasks Used To AssessGeneral Intellectual
Abilities

• WISC-III -all 13 Subtests Composite Scores
• Information Similarities Arithmetic
  Vocabulary Comprehension Digit Span
• Picture Completion Coding Block Design Object
  Assembly Symbol Search Mazes
• Verbal IQ Performance IQ Full Scale IQ
• Verbal Comprehension Perceptual Organization
  Freedom from Distractibility Processing Speed

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Executive Function Tasks

• Working memory
• Fluency Test
  Auditory Working Memory
• Motor Sequencing Speeded Response
• Tactual Performance Task
• Visual Analysis Hypothesis Testing
• Category Test

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Executive Function Tasks (continued)

• Inhibition of Prepotent Response
• Gordon Delay Task (DRL schedule)
• Sustained Attention
• Gordon Vigilance Task

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Discriminant Function Analysis

• Cigarettes
• Primary predictors
• 1/ WISC full-scale IQ
• 2/ Verbal IQ
• 3/ Freedom from Distractibility Index
• 4/ Verbal Comprehension. Index

• Marihuana
• Primary Predictors
• 1/ Category Test
• 2/ Responses on Delay Task
• 3/ WISC Block Design
• 4/ WISC Picture Completion
• 5/ Efficiency Ratio on Delay Task

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Overview of Cognitive Outcomes in 9-12 Year-Olds

• Cigarettes
• IQ impacted
• Many individual WISC tests significant dose
  response effects
• Verbal domain particularly impacted
• No effect on non-verbal Executive Function tasks

• Marihuana
• IQ not impacted
• No individual WISC tests significantly impacted
• DFA Composite score suggests aspect of E. F.
  impacted - Visual Analysis (Block Design, Picture
  Completion Category Test) Impulsivity

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Welsh (1991) E.F. factors identified in
normative sample

• Hypothesis (Visual) Testing Impulse Control
• Fluid Speeded Response
• Planning

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Two Types of Intelligence

• Fluid Intelligence may be highly related to
  Prefrontal lobe Function

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Conclusions

• There is a disassociation between consequences of
  in utero exposure to cigarettes and marihuana.
• Cigarettes impact on overall IQ and
  auditory/verbal domain.
• Marihuana impacts upon a more subtle, top-down,
  integrative process that involves aspects of
  Executive Functioning.

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Facets of Attention are Affected 13-16 year old
Offspring Prenatally Exposed to Marihuana
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Attention Measures Used in Present Report(part
of a large OPPS battery given to the 13-16 year
olds)

• Continuous Performance Task (CPT) - omissions,
  commission, reaction time, change in reaction
  time as test proceeds.
• Wisconsin Card Sort (WCST)- errors, number of
  stimuli.
• Stroop - interference score.
• Arithmetic subtest from WISC.
• Sentence Memory Test.
• Seashore Rhythm Test.
• Knox Cube Test.

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Mirskys 1996 Five Factor Model of Attention
Based on 14 Test Scores

• Focus/execute allocation of attentional
  resources while screening out irrelevant stimuli.
• Shift/flexibility ability to move attention
  across stimuli
• Arouse/exert maintenance of attention over time
• Encode/retain (working memory) mentally holding
  information while utilizing or manipulating it.
• Stability consistency of attention over time

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Restricted Five Factor Solution Conducted on OPPS
Sample Based on 11 Attention VariablesCompared
to Mirskys model -Extracted Variance
Individual Factors are very similar

• Shift/flexibility (like Mirsky - similar tests
  loaded - e.g. Wisconsin Card Sort)
• Encode/Retain (like Mirsky -similar test-WISC
  Arithmetic plus, in present work, Seashore, Knox
  and Sentence Memory loaded)
• Impulsivity (similar to Mirskys arouse/exert
  - CPT variables loaded in both)
• Stability (like Mirsky -CPT variables loaded in
  both)
• Focus/Execute (like Mirsky - Stroop variable
  loaded in both)

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Association of Maternal Smoking Components of
Attention

• Encode/Retain plt.05 after control for
  confounds.
• Impulsivity associated only in the youngest ten
  percent of the sample (13 yrs. 1 month or less)
  at plt.05 after control for confounds.

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Interpretation of Cigarette Findings(Impulsivity)

• Developmentally, inhibitory control (impulsivity)
  stabilizes at approximately 12 yrs of age.
• Consistent with extant literature with younger
  children prenatally exposed to cigarettes,
  tobacco impacts on this domain but, is only seen
  among the youngest children in the present work.
• Beyond 13 yrs, the developmental delay associated
  with in utero exposure has been overcome.

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Interpretation of Cigarette FindingsEncode/Retain

• Developmentally, unlike impulsivity, working
  memory (encode/retain) continues to undergo
  developmental changes until at least 15 years of
  age.
• Thus the impact of prenatal tobacco exposure
  manifests itself across all ages in the present
  work.

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Association of Maternal Marihuana Use
Components of Attention

• Stability has loadings both from CPT reaction
  times that became less consistent as test
  proceeded and increased omission errors. plt.01
  after control of confounds.

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Interpretation of Marihuana FindingsStability

• Findings with respect to omission errors are
  consistent with earlier reports from the OPPS (at
  6 years of age)
• Combination of response variability omission
  errors are a sensitive indicant of performance on
  sustained attention that continues to develop
  throughout adolescence.
• The OPPS marihuana/stability association did not
  interact with age

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Summary

• Results obtained from the 13-16 year old OPPS
  sample are strikingly similar to the five factor
  model proposed by Mirsky.
• Prenatal exposure to cigarettes or marihuana have
  differential consequences upon some of these
  components of attention
• cigarettes impact upon the ability to
  temporarily hold information while processing
  incoming data and, among the younger children, is
  negatively associated with impulse control
• marihuana is associated with sustained
  attentional focus over time

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Visuoperceptual Performance of 9-12 Year Olds
Prenatally Exposed to Marihuana
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Visuoperceptual Tasks

• Fundamental skills (based on the Test of Visual
  Perceptual Skills - TVPS with 7 subtests)
• e.g. visual discrimination
• It has a Summary Score - Perceptual
  Quotient

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Visuoperceptual Tasks

• Visuoperceptual Problem Solving ( based on 4
  tests of the WISC)
• These tests involve the fundamental
  visuoperceptual skills coupled with
  integrative analytical abilities
• e.g. block design
• It has a summary score - Perceptual Index

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Non-perceptual Control Tasks

• I.Q. (WISC)
• Visuomotor (Beery)
• Memory ( digit span)
• Attention (Freedom form Distractibility -
  WISC)

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Results in Cigarette Offspring

• TVPS (fundamental)
• Perceptual Quotient (Summary Score)
• V. Discrimination
• V. Memory
• V. Spatial Relations
• V. Form Constancy
• V. Sequential Memory
• V. Figure-ground
• V. Closure

• Complex Visual-Perceptual
• Perceptual Index Summary Score
• Picture Completion
• Picture Arrangement
• Block Design
• Object Assembly
  sig. before control sig.
  after prenatal P.Q. controls
  

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Results in Marihuana Offspring

• TVPS (fundamental)
• Perceptual Quotient (Summary Score)
• V. Discrimination
• V. Memory
• V. Spatial Relations
• V. Form Constancy
• V. Sequential Memory
• V. Figure-ground
• V. Closure

• Complex Visual-Perceptual
• Perceptual Index Summary Score
• Picture Completion
• Picture Arrangement
• Block Design
• Object Assembly sig. before
  control sig. after prenatal P.Q.
  controls

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The significant association between prenatal
marihuana use and the Perceptual Index (summary
score representing complex visuoperceptual
performance) remainswhen the Perceptual Quotient
(the summary score representing fundamental
visuoperceptual skills) is used as a covariate
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This would suggest that (unlike prenatal
cigarettes)prenatal marihuana affects a
top-down, integrative analytical
visuoperceptual functions as opposed to a basic
visuoperceptual function.
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Patients with frontal lesions do not analyse
the (block design) diagram and they make no
attempt to convert units of impression into
units of construction. They manipulate the
cubes impulsively in accordance with direct
impressions. They do not actively work in order
to complete the test and they do not evaluate
their mistakes.

• Luria - The Working Brain, 1973

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• These marihuana results are consistent with
• 1/ Earlier cognitive observations in which the
  Category Test was the best discriminator of
  prenatal marihuana exposure - it has a high
  factor loading with Picture Completion Block
  Design
• 2/Frontal Lobe patients
• 3/Aspects of Executive Function being impacted by
  prenatal marihuana exposure

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Cognitive Functioning in 13-16 year olds
prenatally exposed to Cigarettes or Marihuana-
Differential Effects
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Background Prenatal Cigarettes

• Lower general cognitive performance in preschool
  school age -dose dependent
• Verbal/auditory processing in a wide range of
  tasks impacted from infancy onward

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Background Prenatal Marihuana

• Not associated with poorer overall cognitive
  performance
• Poorer abstract/visual reasoning first noted at 3
  and 4 yrs of age
• Sustained attention negatively impacted and
  longer latencies on visual search paradigms
• top-down impact- facets of executive function

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Tasks

• General Cognition
• WISC
• Achievement WRAT (reading, spelling
  orally presented, arithmetic)
• Peabody Spelling visual recognition
• Memory
• Auditory (sentence memory)
• Visual (Knox cube)

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Tasks (continued)

• Aspects of Executive Function
• Working Memory Latencies
• Missing numbers (auditory)
• Abstract Designs (visual)
• Perseveration
• WCST
• Response Inhibition
• Stroop

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Significant Cigarette Results

• Before Adjustment
• WRAT Reading
• WRAT Arithmetic
• WISC IQ
• Sentence Memory
• Knox Cube

• After Adjustment
• WISC IQ
• Sentence Memory

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Significant Marihuana Results

• Before Adjustment
• Peabody Spelling
• Abstract Design Latency

• After Adjustment
• Peabody Spelling
• Abstract Design Latency

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Interpretation of Cigarette Findings

• IQ deficits consistent with earlier findings
• Vulnerability of verbal memory also consistent
  with findings at younger ages
• Why achievement tests not significantly related
  while IQ is after statistical adjustment?
• Possibly reflecting formal learning versus
  application of learning in new and different
  situations. Parental Education was major
  confounder

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Interpretation of Marihuana Findings

• Like in this other cohorts at younger ages, IQ
  not related - contrast to prenatal cigarettes.
• Consistent with other reports, complex visual
  behaviour impacted (Peabody spelling versus WRAT
  spelling longer latency but not increased
  errors on abstract design)
• Longer latencies (but not increased errors) also
  noted in visual search tasks in other cohorts.
  Possibly, the longer latencies reflect slower
  processing speed.

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Summary

• Present findings are consistent with and extend
  observations made in this cohort when 9-12 years
  of age and earlier.
• Differential impact of prenatal cigarettes versus
  prenatal marihuana
• Cigarettes impact on overall intelligence and
  verbal aspect of memory
• Marihuana does not impact upon overall
  intelligence but does on tasks requiring visual
  analysis.

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QUESTIONS