Cognitive dysfunction and the inherited predisposition to alcoholism

Journal of Studieson Alcohol, Vol 53, No 2, 1992 Cognitive Dysfunctionand the Inherited Predisposition to Alcoholism* JORDANB PETERSON, PH.D.,PETERR FINN, PH.D., •' ANDROBERTO PIHL, PH.D Departmentof Psychology, McGill University,1205DocteurPenfieldAvenue,Montreal,QuebecH3A lB1, Canada ABSTRACT A batteryof neuropsychological testswasadministered to 22 nonalcoholic sons of male alcoholics (SOMAs) from families with extensive histories of male alcoholism and to 22 nonalcoholic controlswith no historyof familialalcoholism.In eachgroup11 subjects were tested while soberand 11 were testedwhile alcoholintoxicated.Analysesof the resultsof this batterysuggested (1) that SOMAs may be characterized by comparative decrements in those cognitivefunctionsassociated with the organization of novelinformation,dependent in theoryuponthe prefrontalcortex;and (2) that alcoholdetrimentallyaffectsdelayedmemory,associated with the temporalcortex, equallyacrossgroups.Of theseSOMAs 20 had previously participatedin one of two studiesthat demonstratedtheir cardiovascularhyper-reactivity to threat/stressand their increased sensitivityto the reactivity-dampening effectsof alcoholintoxication Correlationalanalysesof the resultsof the presentand previousstudies demonstrated the existenceof a highly significantrelationship between cognitive impairment, cardiovascularhyper-reactivityand susceptibilityto the reactivity-dampening effectsof alcohol.(J Stud Alcohol 53: 154-160, 1992) Granit (1977) reviewedgeneralneuropsychological infor- A VARIETY of studies have demonstrated that the mation suggesting(1) that the prefrontalcortex provides sonsof male alcoholics (SOMAs) are at heightened geneticrisk for the development of alcoholism.None of thesestudiesare abovereproachmethodologicatly (Lester, 1988;Murray et at., 1983;Searles, 1988), but takencollectivelythey suggest that SOMAs are threeto ninetimes morelikely to becomealcoholicthanare the sonsof nonalcoholics(Cloningeret al., 1988; Goodwin, 1985) The precisenatureof this increased risk remainsunknown,but in recentyearsa numberof markersthat appearin association with it have been tentatively identified (Begleiter and Porjesz, 1988) These markershave been described critically,in detail, by Pihl et al (1990) A number of studies have demonstrated that SOMAs performmorepoorly than controlson testsof linguistic ability, abstractionand problem solving(Drejer et al., 1985;Gabrielli and Mednick, 1983;Whipple et at., 1988) Additionalevidenceexistssuggesting that SOMAs hyperreact psychophysiologically to threat and novelty (Finn and Pihl, 1987, 1988; Finn et al., 1990) Tarter et al (1985, 1988) have drawn a parallel betweenthe cognitive and behavioralstylesof SOMAs and of thosewith minor prefrontal corticaltrauma.Gray(1982, 1987),Luria(1980), Vinogradova(1975), Nauta (1974), Sokolov(1969) and Received:September20, 1989 Revision:February27, 1990 *This research wassupported in partby the MedicalResearch Council of Canada *PeterR Finnis withtheDepartment of Psychology, IndianaUniversity, Bloomington,Ind 154 the physiologicalsubstratefor the cognitivefunctionsassociatedwith abstractclassificationand planning;(2) that the prefrontal cortex serves to inhibit or modulate the functionof varioussubcorticalstructures,includingthose governingthreat or novelty response;(3) that the hippocampus and hypothalamusare critically involved in this threatresponse;and (4) that alcoholintoxicationmight interfere with hippocampalfunction Petersonand Pihl (1990), integratingthese sourcesof information, have hypothesizedthat SOMAs have difficulty in abstractlyclassifyingand/orin modulatingtheir reactionto threateningor novel information,perhapsbecause of mild decrementsin prefrontalfunction They suggestalcohol consumptionmight amelioratethe negative subjectiveconsequences of this difficulty associated with increasedphysiological reactivity by interferingwith the function of the novelty/threat response system Three primary hypotheseswere derived from this theory, for the purposesof the presentstudy.It was predicted that (1) soberSOMAs would perform more poorly than controlson cognitivetestsof classificationand planning, generally associatedwith prefrontalfunction; (2) alcohol intoxicationwould interferewith the performanceof both groupson those neuropsychological tests that putatively assesstransferof informationinto long-termmemory,associatedwith the hippocampus; (3) decrements in prefrontal functionamongSOMAs would be correlatedwith their cardiovascular hyper-reactivityto threat.Thesehypotheses PETERSON were to be tested in three parts The first part involved assessment of the neuropsychological function of stringently selectedsober SOMAs and controls, in order to help determineif and in what mannertheir cognitiveabilities differed The secondpart involved a similar assessment, conductedupon intoxicatedSOMAs and controls, in order to help determine primarily what neuropsychological functionsalcoholintoxicationimpairsper se and, further, to investigatewhether SOMAs and controlsdiffer in their susceptibilityto alcohol'seffect on cognition The third part of the study involvedinvestigationof the relationshipbetween the cognitive functioningof these SOMAs and their previously reported (Finn and Pihl, 1987, 1988) cardiovascularreactivity, and sensitivity to dampening(Finn and Pihl, 1987, 1988) of that reactivity by alcoholconsumption ET AL 155 In the secondgroup were 22 men recruitedby newspaper advertisementas paid controls.Healthy nonalcoholic moderate social drinkers (between and 15 drinks/week) with between 13 and 14 yearsof educationwere selected for participation Control subjectshad no identifiable alcoholism(MAST and DSM-III criteria) in the past two generationsof their pedigree Control subjects familiar with psychologicalexperimentationor who had psychotic relativeswere excludedfrom participation.An augmented group of thesesubjectsalso servedas controlsin the concurrentlyrun Petersonet al (1990) study All subjectswere askedto refrain from the consumption of alcohol for 24 hours and from food for hours before the experimentalsession.Subjectswere paid $5 per hour for their participation Design and procedure: Method Parts and Subjects Two groupsof 22 (N = 44) nonalcoholicmen participated in this study All subjectsscored5 or less on the Michigan Alcoholism Screening Test (MAST) (Selzer, 1971) and none could be characterizedas alcohol dependent or abusingby the criteria set forth in the DSM-III (American Psychiatric Association, 1980) Subjects youngerthan 18 and older than 30 yearsof age were excluded from participation Those who completed the study had a mean age, equivalentacrossgroups,of approximately24 years.All subjectswereraisedby their biologicalparents;all were white In the first of thesetwo groupswere SOMAs who had at minimum, in additionto their father, a paternalgrandfather and brother or paternal uncle who were alcoholic accordingto diagnosesmadeat a major Montreal psychiatric institution, where families of alcoholics are screened, interviewed, referred for counselingand recruited as potential subjectsfor a numberof interdisciplinaryresearch efforts At this institution, extensivefamily histories are taken from as many family membersas possible Diagnoses for the interviewed members are based on the MAST and DSM-III criteria Unavailablefamily members are diagnosedaccordingto the Family History Research Diagnostic Criteria (FH-RDC) (Endicott et al., 1975) Subjectsare selectedaccordingto these stringentcriteria in order to increasethe likelihood that they truly are at increasedgenetic risk for the inheritanceof alcoholism This increased risk is reflected in the fact that 76% of the first- and second-degreemale relatives of subjects selected in this fashion are alcoholic (Finn and Pihl, 1987) SOMAs had an averageof 13.4 years of educationand drank between5 and 15 drinks a week Mean age of onset of paternalalcoholismwas 20 years Probandswith alcoholic mothers,with motherswho drank during pregnancy or with psychoticrelativeswere excluded Upon arrival at the laboratory subjectswere familiarized with the experimentalprocedureand were requiredto sign an informed consentform Each subjectwas then randomly assignedto receive either 1.32 ml/kg of 95% pharmaceutical alcoholmixed5:1 in orangejuice or to receive an equivalentamountof juice by body weight and 0.132 ml/kg pharmaceuticalalcohol, to provide "active placebo" (Rossand Pihl, 1989) controlfor subjectand experimenterexpectancy.All subjectswere then submitted to a battery of neuropsychological tests.An independentgroupsdesignwith randomgroup assignmentwas chosen specificallyto control for the effect of practice on the neuropsychological test battery It shouldbe noted additionallythat, althoughexpectancy and dose generallyconfoundthe effectsof a drug (Marlatt and Rohsenow,1980), previousexperiencewith the testbattery usedin this study,within the confinesof a multiple-dosebalanced-placebodesign, indicated that it was insensitiveto the effectsof expectancyand sensitive to the pharmacologicaleffects of a 1.32 ml/kg dose of 95% pure pharmaceuticalalcohol(Petersonet al., 1990) Each subjectwas given three drinks and was asked to finish them within 20 minutes.After a 15-minutewaiting period,eachsubjectwasgiventhe first of threesubjective intoxicationscalesand the first of threebreathalyzertests The former were completedprivately to control for the effectsof experimenterdemand.Subjectswere then taken to a separatetesting area where they were administered the followingtestsin randomorderby threeexperimenters blind to the subject'srisk statusand assignedcondition Thesetestswere chosenfor heuristicpurposes,and were classifiedaccordingly,becausethe cognitiveabilitiesthey test havebeenexperimentallyassociatedwith the function of relatively specific cortical areas It should be noted, however,that there is no simple one-to-onerelationship 156 JOURNAL OF STUDIES ON ALCOHOL betweencortical locale and cognitivefunction Nonetheless, sincethe neuropsychological approachallows in part for analysisof cognitivefunctioningper se, and, further, providesfor the possibilityof clarifyingthe natureof the relationshipbetweencognitionandcorticalfunctioning,its utility outweighsthe inherentrisk of oversimplification Testsof cognitivefunctionoftenassociated with the prefrontal cortex PorteusMaze (extensionseries) Subjectsare required to completea seriesof mazesrankedaccordingto difficulty Individualswith lesionsof the frontallobesdemonstrate impairmentsin their ability to correctlycomplete this test (Crown, 1952; Malmo, 1948; Mettler, 1952) which was designedto measureplanningand foresight (Porteus, 1959) Rey-OsterreithComplexFigure: Copy Subjectsare requiredto copy a complexspatialfigure from an original Individuals with prefrontal damage copy this figure (Lezak, 1976) and complex figures in general (Luria, 1980)poorly•althoughparietaldamagemay alsoproduce performance deficits(Lezak, 1976)of a more severesort ThurstoneWordFluency.Subjectsarerequiredto write as manywordsbeginningwith "S" as possiblein minutes Individuals with left frontaldamageconsistently demonstrateimpairments in word fluency(Benton,1968;Ramier and Hecaen, 1970) which measuresthe ability to generate wordsaccordingto an abstractconceptualcategory Self-OrderedPointing(SOP): 12 representational drawings Subjectsmustpoint to a differentone of 12 pictures of familiar objects,presentedin 12 differentarrays.Individualswith frontal damageconsistentlymanifestdeficits in performance on this task, which requiresthe ability to organizeinformationconceptually.Individualswith temporal damagealso manifestdeficitsthat vary with the severity of their lesion(Petridesand Milner, 1982), although temporallydamagedindividualsalso tend to sufferfrom severememory loss WisconsinCard Sort Test (WCST) Subjectsare presentedsequentially with 64 cards,andare requiredto categorize them according to feedback provided by an investigator Individualssufferingfrom dorso-lateralfrontal lesionsperformpoorly on this test, which is sensitive to perseveration (Grant and Berg, 1948;Milner, 1964) Testsof memoryoftenassociatedwith the temporalcortex WechslerLogical Memory: Immediate and 25-minute delay Subjectsare requiredto repeat two stories, in sequence, once immediately after presentationand once (unknownto them a priori) 25 minuteslater, after completion of a numberof other tasks.Individualswith temporal (particularly hippocampal)damage perform poorly on thesetests,especiallyafter a delay (Milner, 1975) / MARCH 1992 WechslerPaired Associates:Difficult and easy pairs Subjectsare orally presentedthree times with 10 word pairs and are requiredto rememberthe secondword in each pair Six pairs are easy and four difficult to associate Individualswith left temporal(particularlyhippocampal) damagehave difficulty in completingthis test, and thereis additionalevidencethat organicbrain damageparticularlyimpairsrecallof the difficult pairs(Walsh, 1978) Rey-Osterreith Figure: Reproductionfrom memory Subjectsare requiredto redrawthe figure they copied25 minutesearlier, with no a priori knowledgethat they are to so, after completingseveralother tasks Patients with right temporal (particularly hippocampal)damage havedifficulty in completingthis task (Milner, 1975) Testsof cognitivefunction often associatedwith the parietal-occipitalcortex Albert's Test of Visual Neglect Subjectsare given a pencil and a sheetof paper with a numberof short lines printed on it and are asked to bisect each line with anothershortline Subjectswho sufferfrom parietaldamage performparticularlypoorly on this test (Albert, 1973) Apraxia questionnaire.Subjectsare requiredto originate and/or duplicate a number of simple motor operations This questionnaireprovides a general measureof ideomotor,ideationaland buccofacialapraxia, which has been operationallydefined by exclusionas a disorderof skilled movementnot causedby weakness,deafferentiation, abnormaltone or posture,movementdisorder,intellectual deterioration, poor comprehensionor lack of cooperation(Heilman and Valenstein,1985) Miscellaneous tests The Information subtest of the Revised Wechsler Adult IntelligenceScale (WAIS-R) provided a measureof accumulated verbal knowledge The Digit Symbol WAIS-R subtest was included because it is sensitive to variations in motivation(Lezak, 1976) and as a measureof performance IQ A Reaction Time Test, with three subtestsof increasing complexity,wasincludedto assess motorspeed Testswere completedwithin 1.5 hours.Subjectswere given a breath-analyzertest and a subjectiveintoxication scalehalf-way throughand at the end of the test session, debriefed and, upon regaining sobriety (BAC < 04), werepaid $25 and allowedto leave Part Twenty of the 22 SOMAs who volunteered for the presentstudy had previouslyparticipatedin one of two projectsthat demonstrated their augmentedcardiovascular hyper-reactivityto threat/stress and their increasedsensi- PETERSON tivity to the reactivity-dampening effectsof alcohol,in comparisonto matchedcontrols(Finn and Pihl, 1987, 1988) Participantsin these studieswere subjectedto a number of successiveelectric shocks (1.85 mA for 0.25 seconds),whoseonsetwas signaledby a 10-secondcountdown, once while sober and once under the influence of either 1.00 or 1.32 ml of 95% pure pharmaceuticalalco- hol per kg of body weight, in counterbalanced order.In these studies, sober SOMAs from families with extensive male familial alcoholism reacted to the shock procedure with significantincreasesin heart rate (HR) and significantdecreases in digital bloodvolumeamplitude(DBVA) (cardiovascularreactivity) in comparisonto controls, whereaswhenthesesubjectswere alcohol-intoxicated this characteristiccardiovascularhyper-reactivitywas essentially eliminated(cardiovascular reactivitydampening) The theory presentedby Petersonand Pihl (1990) and discussedearlier predictsthat deficits in the cognitive functionsassociatedwith the prefrontalcortex shouldbe accompaniedby increasedcardiovascularreactivity to threat and that alcohol intoxication should eliminate that reactivity.Exploratorycorrelationalanalysescomparing prefrontalfunction,cardiovascular reactivityandalcoholinducedreductionof reactivitywere thereforecompleted Results Parts and The natureof the relationshipbetweenrisk, alcoholintoxication and neuropsychological performancewas ex- ploredstatisticallyby (SOMA/Control)x (Alcohol/ No-Alcohol) analysesof variance (^NOV^), employed separatelyfor each measure.Posthoc testsof simple ET AL 157 main effects were employed in the single case of the Thurstone Word Fluency Test, where interaction effects reachedsignificance Subjectsof each risk statusmaintainedequivalentmean blood alcoholconcentrationsof approximately 10 for the durationof the test periodand ratedthemselves as equally intoxicatedon all three scalesof subjectiveintoxication No subjectsin either groupor conditionmadeany errors while carrying out the tasks associatedwith Albert's Test of Visual Neglect or the apraxia questionnaire.Nevertheless, the analysesdemonstratedtwo primary effects(Table 1) One can be attributed to risk status, the other to the consequences of intoxication With regards solely to risk status:SOMAs manifested comparative decrements in performance on the ReyOsterreith (copy) (F = 5.2, 1/40 df, p < 05), SelfOrderedPointing(F = 11.3, 1/40 dr, p < 001), Difficult PairedAssociates(F = 5.87, 1/40 df, p < 05) andInformation tests(F = 4.8, 1/40 dr, p < 05) With regardssolely to intoxication:Alcohol consumptionimpairedthe performanceof individualsin both risk categories,on the Porteus Maze (F = 4.1, 1/40 df, p < 05), Rey-Osterreith (copy) (F = 5.2, 1/40 dr, p < 05), WisconsinCard Sort (F = 4.1, 1/40 df, p < 05), Easy Paired Associates (F = 5.3, 1/40 dr, p < 05), Difficult Paired Associates (F = 8.2, 1/40 df, p < 01), Delayed Rey-OsterreithFigure (F = 24.7, 1/40 dr, p < 001) and Delayed Logical Memory (F = 15.6, 1.40 dr, p < 001) tests Additionally, SOMAs and controlswere differentiallyaffectedby alcohol while completing the Thurstone Word Fluency Test (F = 5.5, 1/40 df, p < 05), in that the controls were significantly impaired (F = 6.3, 1/40 dr, p < 05) while the SOMAs were not TABLE1 Testsof cognitivefunctionmean(-+ SD) scores Sons of alcoholics No Alcohol Testsassociated with the prefrontalcortex PorteusMaze Age Rey-OsterreithCopy ThurstoneFluency Self-OrderedPointing Wisconsin Card Sort 13.9 -+ '31.7 -+ 3.4 4.6 *38.4 -+ 13.1 *5.4 -+ 1.4 20.4 -+ 9.5 Controls Alcohol No Alcohol Alcohol '12.7-+ 3.1 **26.9 -+ 6.2 '42.1 -+ 10.7 14.9-+ 1.3 32.7 -+ 3.3 *50.0 -+ 9.3 '13.0-+ 1.8 '31.9 -+ 2.4 *39.0 -+ 8.2 *5.8 +- 3.8 *23.7 -+ 6.7 3.3-+ 1.9 14.9 -+ 7.7 3.2-+ 1.4 *22.9 -+ 11.4 Testsassociatedwith the temporalcortex LogicalMemory LogicalMemoryDelay 9.4 -+ 2.8 8.9 -+ 3.2 PairedAssociate(E) PairedAssociate(D) 17.0 +- 1.5 '7.1 -+ 1.5 Rey-Osterreith Delay 20.2 -+ 6.6 Miscellaneous 8.0 +- 3.1 10.6-+ *4.7 '15.4-+ **4.7 -+ '13.0-+ 2.4 2.0 3.3 5.9 9.4 -+ 3.1 17.0-+ 1.5 8.9 -+ 2.1 22.1 _+ 5.8 3.6 8.9-+ 2.7 *6.6 '16.1 +*6.7 -+ '12.4-+ 2.9 2.2 3.2 3.8 *20.7 -+ 4.3 22.8 _+ 3.3 23.4 -+ 2.2 54.4 -+ 37.7 -+ 6.4 5.8 59.3 -+ 7.4 34.8 -+ 6.7 60.0 -+ 33.5 -+ 8.0 5.7 tests Information *20.5 -+ 4.7 Digit Symbol 59.9 +- 9.6 Reaction Time 34.7 -+ 5.8 Riskeffect:*p < 05.Drugeffect:*p < 05 Interaction: *p < 05 Note:Scoresfor the Self-Ordered Pointingarereportedastotalerrorsin threetrialsof 12 Scoresfor the WisconsinCard Sort are reportedastotalerrors in 64 trials 158 T^B[E JOURNAL Correlation OF STUDIES ON ALCOHOL / MARCH 1992 matrix Pearsoncorrelation coefficients (N = 20) HR Increase HR Dampen DBVA Decrease DBVA Dampen Self-OrderedPointing WisconsinCard Sort HR 86 83 73 57 Increase 0001 0001 0002 0082 0007 HR 79 Dampen 0001 73 0003 77 0001 54 0137 DBVA 88 52 69 Decrease 0001 0192 0010 DBVA 42 54 Dampen 0673 69 0140 Self-Ordered 53 Pointing 0169 Part formercase(lst canonicalcorrelationr = 0.75; R2= 0.57; Wilks' lambdaF = 4.2, 4/32 df; p < 008) and in In order to examinethe relationshipbetweenprefrontal function/planningand cardiac hyper-reactivity/alcohol dampening,scoreson the five testsassociated with the prefrontalcortex (PorteusMaze, Rey-Osterreith(copy), Self-OrderedPointing,WisconsinCard Sort andThurstone Word Fluency) were included in a Pearson productmoment correlation matrix along with two indices of soberstress/threat reactivity(HR increaseand DBVA decrease) and two indices of alcohol-intoxication-induced stress/threatreactivity dampening(HR increasereduction the latter(lst canonical correlation r = 0.81;R2 = 0.65; and DBVA decrease reduction) A number of correlation completionof the Self-OrderedPointingTestrequiresthe generationof a workablestrategyfor memoryand intact memoryitself (Petridesand Milner, 1982) Althoughtemporal damage,and subsequent memoryloss,can interfere per se with performanceon this test, testsmost sensitive to temporaldamage(delayedrecall) did not distinguish SOMAs from controls.This suggeststhat comparative lack of organizationaccountsfor their poorer performance.Accuratecopyingof the Rey-Osterreithfigure requiresintact spatialperception,a putative functionof the parietal cortex (Luria, 1980) and the ability to organize complexnovel nonverbalvisual informationinto logical subgroups (Lezak, 1976;Luria, 1980) Althoughbothparietal and frontal damagecan interferewith performance on this test (Lezak, 1976), the fact that SOMAs performedwell on the testsfor apraxiaandneglect,but comparativelypoorlyon otherfrontaltests,suggests that lack of organization,ratherthan impairmentin spatialperception, accountedfor their minor, but statisticallysignifi- coefficientsin this matrix approximatedor exceededthe alpha 0.0025, determinedby Bonferronicorrectionfor matrix size (alpha(0.05) dividedby the numberof correlations of interest (20)) These correlationsare presented in Table It is of interest to note that the correlation betweenWCST performanceand HR increaseimproves when only those who completedthe WCST sober (n = 11) are considered(r = 0.75, p < 009) and falls for those who took the test drunk (r = 0.49, p < 18) This is an importantconsiderationfrom the methodological viewpoint,becausealcoholdetrimentallyaffectedWCST scoresfor both groups.It is also interestingto note that HR reactivity (increase)is highly correlatedwith HR (r = 0.86, p < 0001) and DBVA (r = 0.73, p < 0002) dampening,andthat DBVA reactivity(decrease)is highly correlated with DBVA (r = 0.88, p < 0001) and HR (r = 0.79, p < 0001) dampening Two separatecanonicalcorrelationanalyseswere also conductedto further aid in exploringthe natureof the relationshipbetweenneuropsychological performanceand cardiovascularreactivity and to provisionallydetermine how much of the variance in the latter could be accounted for by the former.The first of theseanalysesexaminedthe relationshipbetween the neuropsychological variables SOP and WCST and HR and DBVA reactivity;the second examinedthe relationshipbetweenSOP/WCST and HR/ DBVA dampening.Significantcorrelations emergedin the Wilks' lambdaF = 6.4, 4/32 df; p < 0004) Discussion Parts and SoberSOMAs could be distinguished from controlsby their performanceon four cognitive tasks: the SelfOrderedPointing, Rey-Osterreith(copy), Difficult Paired Associates and WAIS-R Information tests Successful cant, performancedecrement The developmentof a mnemonicdeviceor anothersim- ilar strategyfor aidingmemoryalsoseemscrucialto successon the Difficult PairedAssociates subtest,althoughit obviouslyalsoinvolvesrecallper se The easywordpairs are matchedaccordingto inherentassociation (e.g., babycries), and one word servesas a cue for the otherduring memorytrials No inherentlymeaningfulassociations exist for the difficultpairs(e.g., crush-dark)andmustthere- PETERSON fore be invented.The fact that SOMAs performedat par with regardsto the easy pairs, but comparativelypoorly on the difficult pairs, suggests onceagainthat SOMAs are characterizedby decrementsin the ability to organizeor categorizeinformation.Althoughnoneof theseindividual tests can be considered conclusive in isolation, the overall pattern of results suggeststhat sober SOMAs may be characterizedby deficitsin the ability to organizeand categorize novel information This ability has been most commonlyassociatedwith the functionof the prefrontal cortex (Luria, 1980) The deficit in accumulated knowl- edge, demonstratedby the Information subtest of the WAIS-R, is a possibleconsequence of this primary dysfunction, which may well have existed in some form since birth Three testsof those cognitive abilities associatedwith the prefrontalcortexprovedmildly sensitiveto the debilitating effectsof alcoholintoxication(PorteusMaze, ReyOsterreithcopy and WisconsinCard Sort Test) However, tho•e cognitiveabilitiesassociated with the functionsof the temporalcortex particularly of the hippocampus-were even more severelyaffected Subjectswho had consumedalcoholwere impairedin their recall of word pairs (Easy and Difficult Paired Associates),in delayedrecall for a narrative(DelayedLogical Memory) and for nonverbal information (Delayed Rey-OsterreithFigure) This pattern of results, equal for both groups, is in keeping with that suggested/reported by Gray (1982) Direct evidence supportingthe contention that alcohol interferes with hippocampalfunctionhasalsorecentlybeenreported (Lovinger et al., 1989) The singleinteractioneffect detectedby the Thurstone Word FluencyTest is interestingand suggests perhapsthat SOMAs are less sensitive to the detrimental effects of al- cohol on word fluency than are controls.It is not unreasonable to supposethat those who are predisposedto abuse alcohol benefit maximally from its positive attributesand suffer minimally from its drawbacks,at least in the short term Part ET AL This means that those who made the most errors dur- ing the SOP weremostsusceptible to the HR reactivitydampeningeffect of alcohol This general line of reasoning is supported by the results of the canonical correlationanalysis.Althoughthis analysisshouldbe consideredexploratorybecauseof the small samplesize involved, it adds credenceto the notion that poorer cognitiveperformanceand increasedcardiovascularreactivity/alcoholdampening are significantly relatedin multigenerationalSOMAs With respectto the relationshipbetweengeneralcardiovascularreactivityand cardiovascular reactivitydampening, soberHR increasewashighlycorrelatedwith alcohol dampeningof that increaseand, similarly,soberDBVA decreasewashighlycorrelatedwith alcoholdampening of that decrease.SoberHR increasewas also highly correlated with DBVA dampeningand, likewise, soberDBVA decreasewas highlycorrelatedwith HR dampening.This combinationof resultssuggeststhat alcohol intoxication essentiallyeliminatesreactivitywithin the confinesof the presentparadigm Conclusion This studyprovidestentativesupportfor the hypothesis that soberSOMAs from familieswith extensivemultigenerationalmale alcoholismare characterized by comparative decrementsin the ability to classifyor to attribute meaningto novelinformation.This ability hasbeenclassically associatedwith prefrontalcortical function This studyalsodemonstrates the existenceof a significantrelationshipbetweencertainaspectsof this cognitivedeficit and the cardiovascularhyper-reactivityand alcoholreactivity-dampening characteristicof such SOMAs and that suchreactivityand dampeningare integrallyrelated In addition, demonstration that alcohol intoxication se- verely impairs the transfer of information from shortterm storage into permanentmemory in SOMAs and controlslendsadditionalcredenceto Gray's (1982, 1987) reportthat alcoholintoxicationparticularlyimpairshippocampalfunction Two particularly interestingpatterns of correlations emergedwith regardsto the theoreticalrelationshipbetween cognitiveperformanceand cardiovascularreactivity: scoreson the WisconsinCard Sort Test (WCST) were highly correlatedwith soberHR increaseand DBVA decrease to signalled shock This means that those who made the most errors during the WCST were most reactive to the signalled shock Scoreson the Self-Ordered PointingTest (SOP) were correlatedsimilarly with sober HR increase and DBVA decrease, although not as strongly.Performanceon both tests was also correlated with alcohol-induced HR and DBVA reactivitydampening, most significantlyfor SOP and HR dampening 159 References ALBERX,M.L A simpletest of visualneglect.NEURA 23: 658-665, 1973 AMERICAN PSYCHIATRIC ASSOCIATION TASK FORCE ON NOMENCLATURE ANDSTATISTICS Diagnosticand StatisticalManual of Mental Disorder, (DSM-III), Washington,D.C., 1980 BEGLEITER, H ANDPORJESZ, B Neurophysiological dysfunctionin alcoholism.In: ROSE,R.M AND BAR•E•'•',J.E (Eds.) Alcoholism: Originsand Outcomes,New York: RavenPress,Pubs., 1988, pp 157-174 BEN•'ON, A.L Differential behavioural effects in frontal lobe disease Neuropsychologia 6: 53-60, 1968 160 JOURNAL OF STUDIES ON ALCOHOL CLONINGER,C.R., SIGVARDSSON, S AND BOHMAN,M Childhoodper- sonalitypredictsalcoholabusein youngadults.Alcsmclin exp Res 12: 494-505, 1988 CROWN,S An experimentalstudyof psychological changesfollowing prefrontallobotomy.J gen Psychol.47: 3-41, 1952 DREJER,K., THEILGAARD,A., TEASDALE,T.W., SCHULSINGER, F AND GOODWIN,W A prospectivestudyof youngmen at high risk for alcoholism:Neuropsychological assessment Alcsmclin exp Res.9: 498-502, 1985 ENDICOTT,J., ANDREASEN, N ANDSPITZER,R.L Family History ResearchDiagnosticCriteria, New York: New York State Psychiatric Institute, Biometrics Research, 1975 FINN, P.R ANDPIHL, R.O Men at high risk for alcoholism:The effect of alcohol on cardiovascularresponseto unavoidableshock J abnorm Psychol.96: 230-236, 1987 FINN, P.R ANDPIHL, R.O Risk for alcoholism:A comparisonbetween two differentgroupsof sonsof alcoholicson cardiovascular reactivity and sensitivityto alcohol.Alcsm clin exp Res 12: 742-747, 1988 FINN, P.R., ZEITOUNI, N.C ANDPIHL, R.O Effects of alcoholon psychophysiological hyperreactivityto nonaversiveand aversivestimuli in men at high risk for alcoholism.J abnorm.Psychol.99: 79-85, 1990 GABRIELLI,W.F., JR AND MEDNICK,S.A Intellectualperformancein children of alcoholics.J nerv merit Dis 171: 444-447, 1983 GOODWIN, D.W Alcoholism and genetics: The sins of the fathers Arch gert Psychiat.42: 937-947, 1985 GRANrr,R The PurposiveBrain, Cambridge,Mass.:MIT Press,1977 GRANT, D.A AND BERG,E.A A behaviouralanalysisof degreeof reinforcementand ease of shifting to new responsesin a Weigl-type card-sortingproblem.J exp Psychol.38: 404-411, 1948 GRAY, J.A The Neuropsychologyof Anxiety: An Enquiry into the Functionsof the Septo-Hippocampal System, New York: Oxford Univ Press, Inc., 1982 GRAY,J.A The Psychologyof Fear and Stress,2d Edition, New York: CambridgeUniv Press, 1987 HElLMAN,K.M ANDVALENSTEiN,E (Eds.) Clinical Neuropsychology, 2d Edition, New York: Oxford Univ Press, 1985 LESTER,D Genetictheory:An assessment of the heritabilityof alcoholism In: CHAVDRON,C.D AND WILKINSON, D.A (Eds.) Theories on Alcoholism,Toronto:Addiction ResearchFoundation,1988, pp 1-28 / MARCH 1992 METTLER, F.A Psychosurgical Problems, Philadelphia: Blakiston, 1952 MILNER, B Some effects of frontal Iobectomy in man In: WARREN, J.M AND AKERT, K (Eds.) The Frontal Granular Cortex and Behaviour, New York: McGraw-Hill Book Co., 1964, pp 313-334 MILNER,B Psychological aspectsof focalepilepsyand its neurosurgical management.In: PURPURA,D.P., PENRY,J.K AND WALTER, R.D (Eds.) Advancesin Neurology, Vol 8, New York: Raven Press, Pubs., 1975, pp 299-321 MURRAY, R.M., CLIFFORD, C.A AND GURLING, H.M.D Twin and adoptionstudies:How good is the evidencefor a geneticrole? In: GALANTER,M (Ed.) RecentDevelopmentsin Alcoholism,Vol 1, New York: PlenumPress, 1983, pp 25-48 NAUTA, W.J.n The problem of the frontal lobe: A reinterpretation Psychiat.Res 8: 167-175, 1974 PETERSON, J.B AND PIHL, R.O Informationprocessing,neuropsychological function, and the inherited predispositionto alcoholism Neuropsych.Rev 1: 343-369, 1990 PETERSON,J.B., ROTHFLEISCH,J., ZELAZO, P.D AND PIHL, R.O Acute alcoholintoxicationand cognitivefunctioning.J Stud Alcohol $1: 114-122, 1990 PETRIDES, M AND MILNER, B Deficits on subject-ordered tasksafter frontal- and temporal-lobelesionsin man Neuropsychologia 20: 249-262, 1982 PORTEUS, S.D The Maze Test and Clinical Psychology,Palo Alto, Calif.: Pacific Books, Pubs., 1959 RAMIER,A.-M ANDHECAEN,n R61erespectifdes atteintesfrontales et de la lat•ralization l•sionelle dans les d•ficits de la "fluence ver- bale." Rev Neurol., Paris 123: 17-22, 1970 Ross, D.F AND PIHL, R.O Modificationof the balanced-placebo design for use at high blood alcohollevels Addict Behav 14: 91-97, 1989 SEARLES, J.S The role of geneticsin the pathogenesis of alcoholism.J abnorm Psychol.97: 153-167, 1988 SELZER,M The Michigan AlcoholismScreeningTest: The questfor a new diagnosticinstrument.Amer J Psychiat.127: 1653-1658,1971 SOKOLOV,E.N The modeling propertiesof the nervoussystem In: COLE,M ANDMALTZMAN,I (Eds.) A Handbookof Contemporary Soviet Psychology,New York: Basic Books, Inc., 1969, pp 671-704 LEZAK,M.D Neuropsychological Assessment, New York: Oxford Univ TARTER,R.E., ALTERMAN,A.I AND EDWARDS, K.L Vulnerabilityto alcoholismin men: A behavior-genetic perspective.J Stud Alcohol Press, Inc., 1976 LOVINGER, D.M., WHITE, G.W AND WEIGHT, F.F Ethanol inhibits TARTER, R.E., NMDA-activatedion currentin hippocampalneurons.Science243: 1721-1724, 1989 LURIA, A.R Higher Cortical Functionsin Man (Haigh, B., transl.), New York: Basic Books, Inc., 1980 MALMO,R.B Psychological aspectsof frontalgyrectomyand frontal lobotomyin mentalpatients.Res Publ Assoc.Res nerv ment Dis 27: 537-564, 1948 MARLATT,G.A AND ROHSENOW, D.J Cognitive processesin alcohol use:Expectancyand the balancedplacebodesign.In: MELLO, N.K (Ed.) Advancesin SubstanceAbuse: Behaviouraland Biological Research, Vol l, Greenwich, Conn.: JAI Press, Inc., 1980, pp 159-189 46: 329-356, 1985 ALTERMAN, A.I AND EDWARDS, K.L Neuro- behaviouraltheory of alcoholismetiology In: CHAUDRON,C.D AND WILKINSON, D.A (Eds.) Theories on Alcoholism, Toronto: Addiction ResearchFoundation,1988, pp 73-102 VINOGRADOVA, O.S Functionalorganizationof the limbic systemin the processof registrationof information: Facts and hypotheses.In: ISAACSON, R.L ANDPRIBRAM, K.H (Eds.) The Hippocampus, Vol 2, New York: PlenumPress,1975, pp 3-69 WALSH, K.W Neuropsychology:A Clinical Approach, New York: Churchill-Livingstone, Inc., 1978 WHIPPLE,S.C., PARKER, E.S ANDNOBLE,E.P An atypicalneurocognitive profile in alcoholicfathersand their sons.J Stud Alcohol49: 240-244, 1988  ... functionsalcoholintoxicationimpairsper se and, further, to investigatewhether SOMAs and controlsdiffer in their susceptibilityto alcohol'seffect on cognition The third part of the study involvedinvestigationof... involvedinvestigationof the relationshipbetween the cognitive functioningof these SOMAs and their previously reported (Finn and Pihl, 1987, 1988) cardiovascularreactivity, and sensitivity to dampening(Finn and Pihl,... were white In the first of thesetwo groupswere SOMAs who had at minimum, in additionto their father, a paternalgrandfather and brother or paternal uncle who were alcoholic accordingto diagnosesmadeat