Cognitive Effects in Adolescents Exposed Prenatally to Marihuana or Cigarettes

1. Cognitive Effects in Adolescents Exposed Prenatally to Marihuana or Cigarettes American Psychiatric Association New York, 2004

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

3. The Ottawa Prenatal Prospective Study

5. Two General Areas • General Cognition and Executive Function • Visuoperception

6. 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

7. 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.

8. Effects of Prenatal Exposure to Marihuana (and Cigarettes) on Cognitive Tasks in 9 to 12 Year-Old Offspring

9. Differential Consequences of the Drugs General Intelligence versus Aspects of Executive Function

10. Executive Functioning which is largely under the control of Prefrontal LobesInvolves • Planning for the future/decision making • Self monitoring/error correction/flexibility/budgeting 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

11. 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

12. The evaluator and evaluation context can become the prosthetic frontal lobes for the subject.

13. 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.)

14. 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

15. Executive Function Tasks • Working memory • Fluency Test Auditory Working Memory • Motor Sequencing & Speeded Response • Tactual Performance Task • Visual Analysis & Hypothesis Testing • Category Test

16. Executive Function Tasks (continued) • Inhibition of Prepotent Response • Gordon Delay Task (DRL schedule) • Sustained Attention • Gordon Vigilance Task

17. 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 Discriminant Function Analysis

18. 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 Overview of Cognitive Outcomes in 9-12 Year-Olds

19. Welsh (1991) E.F. factors identified in normative sample • Hypothesis (Visual) Testing & Impulse Control; • Fluid & Speeded Response; • Planning

20. 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.

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

22. 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

23. 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

24. Non-perceptual Control Tasks • I.Q. (WISC) • Visuomotor (Beery) • Memory ( digit span) • Attention (Freedom form Distractibility - WISC)

25. 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

26. 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 Results in Marihuana Offspring

27. This would suggest that (unlike prenatal cigarettes)prenatal marihuana affects a ‘top-down’, integrative & analytical visuoperceptual functions as opposed to a basic visuoperceptual function.

28. “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

29. 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

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

31. 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

32. 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

33. Tasks General Cognition WISC AchievementWRAT (reading, spelling [orally presented], arithmetic) Peabody Spelling [visual recognition] Memory Auditory (sentence memory) Visual (Knox cube)

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

35. Before Adjustment WRAT Reading WRAT Arithmetic WISC IQ Sentence Memory Knox Cube After Adjustment WISC IQ Sentence Memory Significant Cigarette Results

36. Before Adjustment Peabody Spelling Abstract Design Latency After Adjustment Peabody Spelling Abstract Design Latency Significant Marihuana Results

37. 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

38. 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.

39. 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.

41. QUESTIONS