cognitive effects in adolescents exposed prenatally to marihuana or cigarettes american psychiatric...

Cognitive Effects in Adolescents Exposed Prenatally to Marihuana or

Cigarettes

Cognitive Effects in Adolescents Exposed Prenatally to Marihuana or

Cigarettes

American Psychiatric AssociationAmerican Psychiatric Association

New York, 2004New York, 2004

Prenatal Marihuana Exposure and Its Prenatal Marihuana Exposure and Its Putative Impact Upon Executive Putative Impact Upon Executive

Functioning in Offspring – Functioning in Offspring –

A 25 Year Prospective StudyA 25 Year Prospective Study

The Ottawa Prenatal Prospective Study

The Ottawa Prenatal Prospective Study

Two General AreasTwo General Areas

General Cognition and Executive FunctionGeneral Cognition and Executive Function

VisuoperceptionVisuoperception

Summary of Cigarette Findings0-4 years of age

NewbornNewborn - - auditory responsiveness & habituation; auditory responsiveness & habituation;

tremors & motoric reflexestremors & motoric reflexes 1 year 1 year - - MDI (96 vrs 110) & verbal clusterMDI (96 vrs 110) & verbal cluster.. 2 years 2 years - - MDI (106 vrs 119) & Reynell Expressive & MDI (106 vrs 119) & Reynell Expressive &

Comprehensive. Significance lost when confounds controlled.Comprehensive. Significance lost when confounds controlled. 3 years 3 years - - GCI & language after confounds controlled. GCI & language after confounds controlled.

4 years 4 years - - GCI & language after confounds controlled GCI & language after confounds controlled

Prenatal Marihuana Summary Up To Preschool

Course of pregnancy, fetal and postnatal growth and Course of pregnancy, fetal and postnatal growth and behavior are relatively unaffected during neonatal and behavior are relatively unaffected during neonatal and toddler stagestoddler stages

Starting at approximately 3 years of age converging Starting at approximately 3 years of age converging findings suggest that overall IQ is not affected but findings suggest that overall IQ is not affected but abstract/visual reasoning subscales on IQ tests are abstract/visual reasoning subscales on IQ tests are negatively impacted as are facets of attention.negatively impacted as are facets of attention.

Together, this suggests an impact on aspects of Together, this suggests an impact on aspects of Executive Function - this will be elaborated in a Executive Function - this will be elaborated in a moment.moment.

Effects of Prenatal Exposure to Marihuana (and Cigarettes) on

Cognitive Tasks in 9 to 12 Year-Old Offspring

Differential Consequences Differential Consequences of the Drugsof the Drugs

General Intelligence versus Aspects of Executive

Function

Executive Functioning which is largely under the control of Prefrontal Lobes

Involves Planning for the future/decision makingPlanning for the future/decision making Self monitoring/error correction/flexibility/budgeting of Self monitoring/error correction/flexibility/budgeting of

timetime Working Memory- Integration of past and new Working Memory- Integration of past and new

informationinformation Control over dominant responsesControl over dominant responses Attention allowing control of interferenceAttention allowing control of interference The Prefrontal lobes allow us to respond The Prefrontal lobes allow us to respond

-not simply react-not simply react

Paradox of Executive System Assessment

Paradox of Executive System Assessment

Trying to assess ability to set goals, plan & Trying to assess ability to set goals, plan & organize behavior in pursuit of those goals, organize behavior in pursuit of those goals, and flexibly solve problems in the context of and flexibly solve problems in the context of

an unstructured real worldan unstructured real world

YETYET

using a test situation in whichusing a test situation in which

highly structured tasks are presented in a highly highly structured tasks are presented in a highly controlled environmentcontrolled environment

The evaluator and evaluation context can become the

prosthetic frontal lobes for the subject.

The evaluator and evaluation context can become the

prosthetic frontal lobes for the subject.

Poor Executive Function A dysregulation of goal directed behaviour A dysregulation of goal directed behaviour not attributable to a more basic deficit in not attributable to a more basic deficit in

perception, memory, or language comprehensionperception, memory, or language comprehension Occurs across tasks varying in content & surface Occurs across tasks varying in content & surface

characteristicscharacteristics Despite understanding goal of task, prefrontal Despite understanding goal of task, prefrontal

dysfunction results in impaired performance dysfunction results in impaired performance (intrusions of task irrelevant behaviour, (intrusions of task irrelevant behaviour, perseveration, lack of initiative etc.)perseveration, lack of initiative etc.)

Tasks Used To AssessGeneral Intellectual Abilities

WISC-III -all 13 Subtests & Composite Scores :WISC-III -all 13 Subtests & Composite Scores : Information; Similarities; Arithmetic; Vocabulary; Information; Similarities; Arithmetic; Vocabulary;

Comprehension; Digit SpanComprehension; Digit Span Picture Completion; Coding; Block Design; Object Picture Completion; Coding; Block Design; Object

Assembly; Symbol Search; MazesAssembly; Symbol Search; Mazes Verbal IQ; Performance IQ; Full Scale IQVerbal IQ; Performance IQ; Full Scale IQ Verbal Comprehension; Perceptual Organization; Verbal Comprehension; Perceptual Organization;

Freedom from Distractibility; Processing SpeedFreedom from Distractibility; Processing Speed

Executive Function Tasks Working memoryWorking memory Fluency Test Fluency Test

Auditory Working MemoryAuditory Working Memory Motor Sequencing & Speeded ResponseMotor Sequencing & Speeded Response Tactual Performance Task Tactual Performance Task Visual Analysis & Hypothesis TestingVisual Analysis & Hypothesis Testing Category TestCategory Test

Executive Function Tasks (continued) Inhibition of Prepotent ResponseInhibition of Prepotent Response Gordon Delay Task (DRL schedule)Gordon Delay Task (DRL schedule) Sustained AttentionSustained Attention Gordon Vigilance TaskGordon Vigilance Task

Discriminant Function Analysis Cigarettes Primary predictorsPrimary predictors 1/ WISC full-scale IQ1/ WISC full-scale IQ 2/ Verbal IQ2/ Verbal IQ 3/ Freedom from 3/ Freedom from

Distractibility IndexDistractibility Index 4/ Verbal 4/ Verbal

Comprehension. IndexComprehension. Index

Marihuana Primary PredictorsPrimary Predictors 1/ Category Test1/ Category Test 2/ Responses on Delay Task2/ Responses on Delay Task 3/ WISC Block Design3/ WISC Block Design 4/ WISC Picture Completion4/ WISC Picture Completion 5/ Efficiency Ratio on Delay 5/ Efficiency Ratio on Delay

TaskTask

Overview of Cognitive Outcomes in Overview of Cognitive Outcomes in 9-12 Year-Olds9-12 Year-Olds

Overview of Cognitive Outcomes in Overview of Cognitive Outcomes in 9-12 Year-Olds9-12 Year-Olds

CigarettesCigarettes IQ impactedIQ impacted Many individual WISC Many individual WISC

tests significant dose tests significant dose response effectsresponse effects

Verbal domain Verbal domain particularly impactedparticularly impacted

No effect on non-verbal No effect on non-verbal Executive Function tasksExecutive Function tasks

MarihuanaMarihuana IQ not impactedIQ not impacted No individual WISC tests No individual WISC tests

significantly impactedsignificantly impacted DFA Composite score suggests DFA Composite score suggests

aspect of E. F. impacted - aspect of E. F. impacted - Visual Analysis (Block Visual Analysis (Block Design, Picture Completion & Design, Picture Completion & Category Test) + ImpulsivityCategory Test) + Impulsivity

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

Hypothesis (Visual) Testing & Impulse Control;

Fluid & Speeded Response; Planning

ConclusionsConclusionsConclusionsConclusions There is a disassociation between There is a disassociation between

consequences of in utero exposure to consequences of in utero exposure to cigarettes and marihuana.cigarettes and marihuana.

Cigarettes impact on overall IQ and Cigarettes impact on overall IQ and auditory/verbal domain.auditory/verbal domain.

Marihuana impacts upon a more subtle, Marihuana impacts upon a more subtle, ‘top-down’, integrative process that ‘top-down’, integrative process that involves aspects of Executive Functioning.involves aspects of Executive Functioning.

Visuoperceptual Performance of 9-12 Year Olds Prenatally

Exposed to Marihuana

Visuoperceptual Tasks

Fundamental skills Fundamental skills (based on the Test of (based on the Test of Visual Perceptual Skills - [TVPS] with 7 Visual Perceptual Skills - [TVPS] with 7 subtests)subtests)

e.g. visual discriminatione.g. visual discrimination It has a Summary Score - It has a Summary Score - Perceptual Perceptual

QuotientQuotient

Visuoperceptual Tasks

Visuoperceptual Problem Solving ( based on Visuoperceptual Problem Solving ( based on 4 tests of the WISC)4 tests of the WISC)

These tests involve the fundamental These tests involve the fundamental visuoperceptual skills coupled with visuoperceptual skills coupled with integrative & analytical abilitiesintegrative & analytical abilities

e.g. block designe.g. block design It has a summary score - It has a summary score - Perceptual Perceptual

IndexIndex

Non-perceptual Control Tasks

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

WISC)WISC)

Results in Cigarette OffspringResults in Cigarette Offspring

TVPS (fundamentalTVPS (fundamental)) Perceptual QuotientPerceptual Quotient** **

(Summary Score)(Summary Score) V. Discrimination**V. Discrimination** V. Memory*V. Memory* V. Spatial Relations**V. Spatial Relations** V. Form Constancy**V. Form Constancy** V. Sequential Memory**V. Sequential Memory** V. Figure-groundV. Figure-ground V. Closure*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

TVPS (fundamentalTVPS (fundamental)) Perceptual Quotient Perceptual Quotient

(Summary Score)(Summary Score) V. DiscriminationV. Discrimination V. MemoryV. Memory V. Spatial RelationsV. Spatial Relations V. Form ConstancyV. Form Constancy V. Sequential MemoryV. Sequential Memory V. Figure-groundV. Figure-ground V. ClosureV. 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

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

“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, Luria - The Working Brain, 19731973

These marihuana results are consistent withThese marihuana results are consistent with 1/ Earlier cognitive observations in which the 1/ Earlier cognitive observations in which the

Category Test was the best discriminator of Category Test was the best discriminator of prenatal marihuana exposure - it has a high prenatal marihuana exposure - it has a high factor loading with Picture Completion & factor loading with Picture Completion & Block DesignBlock Design

2/Frontal Lobe patients2/Frontal Lobe patients 3/Aspects of Executive Function being 3/Aspects of Executive Function being

impacted by prenatal marihuana exposureimpacted by prenatal marihuana exposure

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

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

Background Prenatal Cigarettes

Background Prenatal Cigarettes

Lower general cognitive performance in Lower general cognitive performance in preschool & school age -dose dependentpreschool & school age -dose dependent

Verbal/auditory processing in a wide range Verbal/auditory processing in a wide range of tasks impacted from infancy onwardof tasks impacted from infancy onward

Background

Prenatal Marihuana

Background

Prenatal Marihuana Not associated with poorer overall cognitive Not associated with poorer overall cognitive

performanceperformance Poorer abstract/visual reasoning first noted Poorer abstract/visual reasoning first noted

at 3 and 4 yrs of ageat 3 and 4 yrs of age Sustained attention negatively impacted and Sustained attention negatively impacted and

longer latencies on visual search paradigmslonger latencies on visual search paradigms ‘‘top-down’ impact- facets of executive top-down’ impact- facets of executive

function function

TasksTasksGeneral CognitionGeneral Cognition

WISC WISC

AchievementAchievementWRAT (reading, spelling [orally presented], arithmetic)WRAT (reading, spelling [orally presented], arithmetic)

Peabody Spelling [visual recognition]Peabody Spelling [visual recognition]

MemoryMemoryAuditory (sentence memory)Auditory (sentence memory)

Visual (Knox cube)Visual (Knox cube)

Tasks (continued)Tasks (continued)

Aspects of Executive FunctionAspects of Executive FunctionWorking Memory & LatenciesWorking Memory & Latencies

Missing numbers (auditory)Missing numbers (auditory)Abstract Designs (visual)Abstract Designs (visual)

PerseverationPerseverationWCST WCST

Response InhibitionResponse InhibitionStroopStroop

Significant Cigarette Results Significant Cigarette Results

Before AdjustmentBefore Adjustment WRAT ReadingWRAT Reading WRAT ArithmeticWRAT Arithmetic WISC IQWISC IQ Sentence MemorySentence Memory Knox CubeKnox Cube

After AdjustmentAfter Adjustment

WISC IQWISC IQ Sentence MemorySentence Memory

Significant Marihuana Results Significant Marihuana Results

Before AdjustmentBefore Adjustment Peabody SpellingPeabody Spelling Abstract Design LatencyAbstract Design Latency

After AdjustmentAfter Adjustment Peabody SpellingPeabody Spelling Abstract Design LatencyAbstract Design Latency

Interpretation of Cigarette FindingsInterpretation of Cigarette Findings IQ deficits consistent with earlier findingsIQ deficits consistent with earlier findings Vulnerability of verbal memory also Vulnerability of verbal memory also

consistent with findings at younger agesconsistent with findings at younger ages Why achievement tests not significantly Why achievement tests not significantly

related while IQ is after statistical related while IQ is after statistical adjustment?adjustment?

Possibly reflecting formal learning versus application Possibly reflecting formal learning versus application of learning in new and different situations. Parental of learning in new and different situations. Parental Education was major confounder Education was major confounder

Interpretation of Marihuana FindingsInterpretation of Marihuana Findings

Like in this & other cohorts at younger ages, IQ not related Like in this & other cohorts at younger ages, IQ not related - contrast to prenatal cigarettes.- contrast to prenatal cigarettes.

Consistent with other reports, complex visual behaviour Consistent with other reports, complex visual behaviour impacted (Peabody spelling versus WRAT spelling; longer impacted (Peabody spelling versus WRAT spelling; longer latency [but not increased errors] on abstract design)latency [but not increased errors] on abstract design)

Longer latencies (but not increased errors) also noted in Longer latencies (but not increased errors) also noted in visual search tasks in other cohorts. Possibly, the longer visual search tasks in other cohorts. Possibly, the longer latencies reflect slower processing speed.latencies reflect slower processing speed.

SummarySummary

Present findings are consistent with and extend Present findings are consistent with and extend observations made in this cohort when 9-12 years of age observations made in this cohort when 9-12 years of age and earlier.and earlier.

Differential impact of prenatal cigarettes versus prenatal Differential impact of prenatal cigarettes versus prenatal marihuanamarihuana

Cigarettes impact on overall intelligence and verbal aspect Cigarettes impact on overall intelligence and verbal aspect of memoryof memory

Marihuana does not impact upon overall intelligence but Marihuana does not impact upon overall intelligence but does on tasks requiring visual analysis.does on tasks requiring visual analysis.

QUESTIONSQUESTIONS