ALDH2 genotype-associated differences in the acute effects of alcohol on P300, psychomotor...

ALDH2 genotype-associated differences in the acuteeffects of alcohol on P300, psychomotor performance,and subjective response in healthy young Korean men: adouble-blind placebo-controlled crossover study

Hee-Young Shin1, Il-Seon Shin2 and Jin-Sang Yoon 1,2*

1Clinical Trial Center, Chonnam National University Hospital, Kwangju, Korea2Department of Psychiatry, Chonnam National University Medical School, Kwangju, Korea

Background This study investigated the acute effects of alcohol on neurophysiological and psychomotor functions and thesubjective response in healthy young Korean men according to the mitochondrial aldehyde dehydrogenase (ALDH2)genotype.Method A total of 24 males, half with ALDH2�1/�1 (active form) and the rest with ALDH2�1/�2 (inactive form), wereselected through genotyping. In a double-blind placebo-controlled crossover design, each subject consumed either a 0.5 g/kgdose of alcohol or a placebo on two separate occasions, 1 week apart. The blood alcohol concentrations (BACs), P300 ofevent-related potential, psychomotor performance, and perceived feelings were assessed.Results Although the BACs were similar between the two groups, the effects of alcohol on P300 were greater overall insubjects with ALDH2�1/�2 than in subjects with ALDH2�1/�1. Psychomotor performance was more impaired after alcoholingestion in subjects with ALDH2�1/�2 than in subjects with ALDH2�1/�1. The subjective response after alcohol ingestionwas more negative in subjects with ALDH2�1/�2, compared to subjects with ALDH2�1/�1.Conclusions These results suggest that the ALDH2 polymorphism is an important factor in determining the effects ofalcohol on various psychobehavioral functions. Copyright # 2006 John Wiley & Sons, Ltd.

key words—alcohol; ALDH2; p300; psychomotor performance; subjective response

INTRODUCTION

Mitochondrial aldehyde dehydrogenase (ALDH2) isresponsible for metabolizing acetaldehyde, the firstbreakdown product of alcohol. The ALDH2 gene hasALDH2�1 and ALDH2�2 alleles, and genotypingshows three genotypes: ALDH2�1/�1, ALDH2�1/�2,and ALDH2�2/�2 (Crabb et al., 1989; Goedde et al.,1989; Wall and Ehlers, 1995). The deficient pheno-type of ALDH2 has been shown to correspond to the

ALDH2�1/�2 and ALDH2�2/�2 genotypes and isfound in approximately 30–50% of Asians (Hsuet al., 1987; Thomasson et al., 1991). This enzymedeficiency, which results in increased blood acet-aldehyde levels, seems to be responsible for the facialflushing and physiological distress experienced bymany Asians after the intake of a small amount ofalcohol (Wolff, 1972; Goedde et al., 1979, 1983;Mizoi et al., 1979, 1983). Furthermore, it has beensuggested that this adverse physiological reaction maybe an important factor in protecting against alcoholabuse, as may be seen in the low incidence ofalcoholism in Asians (Agarwal and Goedde, 1990;Yoshida, 1993; Kim et al., 2004).Data on the differences in alcohol-induced central

nervous system (CNS) effects between individualswith the active ALDH2 genotype and those with theinactive ALDH2 genotype are very rare in terms of

human psychopharmacologyHum Psychopharmacol Clin Exp 2006; 21: 159–166.

Published online 24 March 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hup.755

*Correspondence to: Professor J.-S. Yoon, Department of Psychia-try, Chonnam National University Medical School, 5 Hak-dongDong-ku, Kwangju 501-746, Korea. Tel: þ82-62-220-6142; Fax:þ82-62-225-2351.E-mail: [email protected]

Contract/grant sponsor: Ministry of Health & Welfare, Republic ofKorea; contract/grant number: A0S0174.

Copyright # 2006 John Wiley & Sons, Ltd.

Received 19 October 2005

Accepted 4 January 2006

objective measurements. In order to compare the acuteeffects of alcohol on the CNS between ALDH2�1/�1and ALDH2�1/�2 groups, the P300 components ofevent-related potential (ERP) (Wall and Ehlers, 1995)and electroencephalographic (EEG) activities(Nishimura et al., 2001) were investigated. Bothstudies found some significant differences in neuro-physiological substrates between the groups afteralcohol ingestion; nonetheless, psychomotor functionwas not evaluated. To determine the effects of alcoholon psychomotor function in different ALDH2 varia-tions, Yoon and Yoon (1996) administered a battery ofpsychomotor tests. Unfortunately, the genotyping intheir study was conducted using an ethanol patch test,which is an indirect and unsatisfactory method(Yokoyama et al., 1997; Takeshita et al., 2001),and it appears that the genotypes of the selectedsubjects were not accurate.No previous study has examined the effects of alcohol

on various psychobehavioral parameters according toALDH2 genotype. This study investigated the acuteeffects of alcohol on P300, psychomotor performance,and the subjective response in healthy young Koreanmen according to ALDH2 genotype.

METHODS

Subjects

Subjects were healthy young men who volunteered forthe study. At screening, all subjects were evaluated byclinical interview, physical examination, and psychia-tric assessment, using questionnaires for drinkinghistory and habits, a Korean version of the MinnesotaMultiphasic Personality Inventory (MMPI) (Kimet al., 1989), the State-Trait Anxiety Inventory (STAI)(Spielberger et al., 1970), and the circadian rhythmquestionnaire (Korean version of the morningness–eveningness questionnaire) (Yoon et al., 1997).Eligible subjects were required to be male, aged19–25 years; to have the intermediate type of circadianrhythm; to be within the normal range on the MMPIprofile; and to be within the normal range on the STAI.Subjects were excluded from the study if they wereknown to have a physical or mental disorder; to havetaken any medications that might interfere with theirdaily life in the last month; to be very sensitive toalcohol or to have a history of alcohol or other drugabuse; to have a family history of alcohol dependenceor abuse in their first-degree relatives; or to have theALDH2�2/�2 genotype, since they could not tolerate a0.5 g/kg dose of alcohol.

Through the screening process and genotypingusing the amplification created restriction site (ACRS)method with minor modifications (Harada and Zhang,1993), 24 subjects (12 with ALDH2�1/�1 and 12 withALDH2�1/�2) participated in the study. This studywas approved by Chonnam National UniversityHospital Review Board. The purpose and details ofthe study were explained to all subjects, and informedconsent was obtained.

Procedure

In a double-blind, placebo-controlled crossoverdesign, each subject had either a 0.5 g/kg dose ofalcohol, given as a mixture of 40% (80 proof) vodkaand orange juice, or a placebo (orange juice) on twoseparate occasions (on average, 1 week apart). Eachsubject drank the test or placebo beverage in randomsequence at the two time points. Each beverage wasmade to a volume of 300ml and consumed over15 min at 58C from an opaque bottle, through a stopperpacked with vodka soaked cotton wool, to provideolfactory masking. Prior to testing, subjects werefamiliarized with the procedures. The timeline foreach evaluation session is shown in Table 1. Smokingwas not allowed from 30 min prior to preparing for theP300 of ERP to the end of the assessment. The bloodalcohol concentration (BAC) was measured using abreath analyzer Alco-Sensor IV (Intoximeters, St.Louis, MO, USA) at baseline, and 30 and 60 min afterdrinking.

P300 of event-related potential

The P300 is a measure of neurophysiological function,reflecting cognitive processing (Polich and Kok,1995). The P300 was measured by topographic brainimaging (Brain Atlas version 2.35 Model 688; Bio-Logic Systems Corp., Mundelein, IL, USA). P300amplitude and latency were elicited using an oddball

Table 1. The timeline for each evaluation session

Time (h) Activities or assessments

17:30 Arrive at laboratory and screening for recent alcoholconsumption by breath measurement of the bloodalcohol concentration (BAC)

18:00 Dinner19:00 Preparation for event-related potential (ERP)19:30 Baseline assessments: ERP and psychomotor tests20:15 Alcohol (0.5 g/kg) or placebo intake over 15 min21:00 BAC & ERP21:30 BAC, psychomotor tests, & questionnaire

for subjective response

Copyright # 2006 John Wiley & Sons, Ltd. Hum Psychopharmacol Clin Exp 2006; 21: 159–166.

160 h. y. shin ET AL.

procedure by auditory stimuli (Wall and Ehlers,1995). Two tones of auditory stimuli were used:standard tone (1000Hz, 70 dB) and rare (target) tone(2000Hz, 70 dB). The ratio of standard tone to raretone was four. Subjects were instructed to count therare tone each time they detected it. ERPs measured 50times were averaged, and the P300 was determined bythe greatest positive potential between 250 and500msec. Electrodes were placed at central (Cz),frontal (Fz), and parietal (Pz) regions, whereamplitude and latency were measured. The base-line-to-peak amplitude (in mV) was identified, and theP300 latency (in msec) was defined as the time to thepeak amplitude after stimulus presentation.

Psychomotor performance

Critical flicker fusion threshold (CFFT ). The CFFT isa means of measuring the ability to distinguish units ofsensory data and is taken as an index of the state ofarousal of the CNS (Hindmarch, 1982; Hindmarchet al., 1990, 1991). Subjects were required todiscriminate flicker from fusion in a set of four lightemitting diodes held in foveal fixation at 1m.Individual thresholds were determined by the psy-chophysical method of limits on three ascending andthree descending scales.

Choice reaction time (CRT). The CRT is a measureof sensorimotor reaction to a critical stimulus(Hindmarch et al., 1988). From a central startingposition, subjects were required to extinguish one ofsix equidistant red lights illuminated at random bytouching the appropriate response button next to thelight. The test provides three measures: RecognitionReaction Time (RRT) (time to notice the stimulus),Motor Reaction Time (MRT) (time to respond bypressing the appropriate button), and Total ReactionTime (TRT).

Digit symbol substitution test (DSST ). The DSSTmeasures general cognitive efficiency and visuo-motor coordination. In the present study, the subset ofthe Korean–Wechsler Adult Intelligence Scale (Yumet al., 1992) was applied for the DSST. The number ofcorrect substitutions in 90 sec was the responsemeasure taken.

Subjective response

A questionnaire for subjective response was adminis-tered, consisting of 12 items relating to psychophysio-logical condition: facial warmness, facial flushing,

chest palpitation, dizziness, headache, nausea/vomiting, sleepiness, gastric discomfort, dry mouth,general weakness, drunken feeling, and psychomotorincoordination. It was designed for this study withreference to the Michigan Alcohol Screening Test(Selzer, 1971) and other studies (Wolff, 1972; Mizoiet al., 1983; Schuckit, 1984; Ohmori et al., 1986;Pollock et al., 1986). Subjects were instructed to recordthe magnitude of the change in their behavioral stateexperienced following beverage intake. The score foreach item ranged from 0 (not at all) to 6 (extremelysevere).

Statistical analysis

The characteristics and BACs of subjects in theALDH2�1/�1 and ALDH2�1/�2 groups were com-pared using a t-test. In the analyses of the variables onthe P300 and psychomotor performance, three-wayrepeated measures ANOVAwas fitted with factors fortime (pretreatment and posttreatment) and drug(placebo and alcohol) as within-subject factors andfor group (ALDH2�1/�1 and ALDH2�1/�2 genotype)as the between-subject factor. For the subjectiveresponse, two-way repeated measures ANOVA wasfitted with factors for drug (placebo and alcohol) as thewithin-subject factor and for group (ALDH2�1/�1 andALDH2�1/�2 genotype) as the between-subject factor.A p-value of less than 0.05 was used to indicatestatistical significance, and statistical analysis wasdone using SPSS 12.0 (SPSS Inc., Chicago, IL, USA).

RESULTS

There were no significant differences between theALDH2�1/�1 and ALDH2�1/�2 groups for age, traitanxiety, circadian rhythm, or drinking history andhabits (see Table 2). The BACs 30 and 60 minafter the consumption of alcohol were equivalent forthe ALDH2�1/�1 (0.039� 0.010 g/dl; 0.034�0.008 g/dl) and ALDH2�1/�2 (0.042� 0.009 g/dl;0.035� 0.006 g/dl) groups (p¼ 0.40; p¼ 0.64).Data on P300 and psychomotor performance are

presented graphically in Figure 1 and 2, respectively.The results of repeated measures ANOVAs for P300and psychomotor performance are shown in Table 3.The effects of alcohol on the P300 latency in Fz, Cz,and Pz, and the P300 amplitude in Fz weresignificantly greater in subjects with ALDH2�1/�2than in subjects with ALDH2�1/�1. Psychomotorperformance on CFFT, MRT, TRT, and DSST wassignificantly more impaired after alcohol ingestion insubjects with ALDH2�1/�2 than in subjects withALDH2�1/�1.


aldh2 genotype-associated differences in effects of alcohol 161

With respect to the subjective response, alcoholhad a more negative effect overall in subjects withALDH2�1/�2, compared to subjects with ALDH2�1/�

1. There were significant effects of group and group�drug interaction on all items (all p< 0.05; data notshown).

DISCUSSION

The results support that ALDH2 polymorphism is animportant factor in determining the alcohol effects onvarious psychobehavioral functions. To interpret theresults of the study and compare them with those ofother studies, the following characteristics of thepresent study should be considered. First, this studyprovided various aspects of the acute effects ofalcohol, including its effects on neurophysiologicaland psychomotor functions, as well as the subjectiveresponse; previous studies had focused on aspects ofthe responses to alcohol that were relatively limited.Second, the 0.5 g/kg dose of alcohol used in this studywas chosen to avoid the ethical problems that mighthave occurred if higher doses of alcohol had beenapplied. This level of alcohol would commonly beconsumed in social drinking. Third, this study wasperformed in the evening, when social drinkingusually occurs; previous studies had been undertakenin the daytime. It was reported that although the BACin the daytime did not differ from that in the evening,alcohol impaired the psychological response more in

the evening than it did in the daytime due to thecircadian rhythm (Lawrence et al., 1983).

Drinking history and habits were similar for theALDH2�1/�1 and ALDH2�1/�2 groups. This lack ofdifference between the two groups might have beendue to the strict exclusion criteria, which ruled outsubjects with alcohol-related disorders and those whowere very sensitive to alcohol. However, it is morelikely because the study participants had a relativelyshort drinking history, in that they were only in theirlate teens or early 20s.

There was no significant difference between theALDH2�1/�1 and ALDH2�1/�2 groups with respect toBAC, as previous studies have reported (Kim et al.,1985; Adachi et al., 1991). Since the ALDH2 enzymeis involved in metabolizing acetaldehyde to acetate, itis thought that the activity of ALDH2 can affect theconcentration of acetaldehyde, but probably not BAC.

Generally P300 latency is increased and the P300amplitude is decreased after the acute ingestion ofalcohol (Campbell and Lowick, 1987; Michel andBattig, 1989). Wall and Ehlers (1995) reported thatalcohol had a greater effect compared to the placeboon P300 in subjects with ALDH2�1/�2 than in subjectswith ALDH2�1/�1, despite equivalent BACs. Ourstudy found that the effects of alcohol on P300 latencyin Fz, Cz, and Pz, and the P300 amplitude in Fz weregreater in subjects with ALDH2�1/�2 than in subjectswith ALDH2�1/�1.

It is generally agreed that relatively high doses ofalcohol (i.e., above 0.8 g/kg) suppress CNS functionand impair psychomotor performance (Hindmarchet al., 1991). With small to moderate doses (0.1–0.8 g/kg), however, the variation in the results makesgeneralization more difficult. For example, Palva et al.(1979) reported that psychomotor performance wasimproved after 0.5 and 0.8 g/kg of alcohol ingestion,whereas Fagan et al. (1987) determined that 0.2, 0.4,and 0.8 g/kg of alcohol had no effect on psychomotorperformance. These variations in the effects of smallto moderate doses could result from many factors:development of tolerance, variable sensitivity toethanol, intra- and inter-individual differences inabsorption, metabolism, and drinking habits, taskfamiliarities/complexities, and experimental design.In this regard, the ALDH2 genotype can be animportant determinant, considering that alcohol-related physiological responses and patterns of alcoholuse differ according to ALDH2 genotype.

However, very few studies have evaluated theeffects of alcohol on psychomotor performance insubjects with different ALDH2 genotypes. Yoon andYoon (1996) attempted to evaluate the effects of

Table 2. Characteristics of the subjectsa

Characteristics ALDH2�1/�1(n¼ 12)

ALDH2�1/�2(n¼ 12)

Age, years 21.8 (2.0) 22.7 (2.3)Trait anxiety, scoresb 40.6 (6.2) 40.5 (6.1)Circadian rhythm questionnaire,scoresc

35.3 (3.8) 36.9 (3.3)

Drinking history and habitsAge of beginning, years 18.3 (1.3) 18.2 (1.5)Frequency per month 7.3 (4.3) 5.8 (3.6)

Average amount per drinking session,bottled

Beer 2.2 (1.2) 1.5 (0.6)Soju 1.0 (0.8) 0.7 (0.4)

aValues are the mean (standard deviation).bAssessed using Spielberg’s Trait Anxiety Scale.cAssessed using the Korean version of the morningness-eveningnessquestionnaire.dThe volume of a bottle was 500ml for beer and 300ml for soju.Soju is a Korean alcoholic drink similar to vodka; it contains 25%alcohol per volume.There were no significant differences between the ALDH2�1/�1 andALDH2�1/�2 groups for all variables.



various doses of alcohol on psychomotor performancein the ALDH2�1/�1 and ALDH2�1/�2 groups. Theyfound various effects, depending on the genotype andthe dose of alcohol: a relatively high dose (1.0 g/kg)caused deterioration in psychomotor performance inboth groups and it was more severe in subjects withALDH2�1/�2. Conversely, a moderate dose (0.5 g/kg)improved psychomotor performance in subjects withALDH2�1/�1, while it impaired performance insubjects with ALDH2�1/�2.

Our study classified the subjects into two groupsusing appropriate genotyping, and found that psycho-motor function was slightly improved after a 0.5 g/kg

dose of alcohol ingestion in subjects withALDH2�1/�1, whereas it was impaired in subjectswith ALDH2�1/�2. This indicates that a moderate doseof alcohol (0.5 g/kg) might have opposite effects,depending on the ALDH2 genotype. Furthermore, onesocial implication is that individuals withALDH2�1/�2 with a BAC within the legal limit couldbe impaired in terms of driving and operatingmachinery.The subjective response after drinking was more

negative in subjects with ALDH2�1/�2, compared tosubjects with ALDH2�1/�1. Regarding the reasonwhy the subjective response and a number of

Figure 1. P300 latency (msec) and amplitude (mV) before and after the intake of placebo or 0.5 g/kg alcohol in subjects with ALDH2�1/�1and ALDH2�1/�2. Fz, frontal lead; Cz, central; Pz, parietal.



Figure

2.

Psychomotorperform

ance

before

andaftertheintakeofplaceboor0.5g/kgalcoholin

subjectswithALDH2� 1/�1andALDH2� 1/�2.CFFT,criticalfli cker

fusionthreshold;

DSST,digitsymbolsubstitutiontest;CRT,choicereactiontime;

RRT,recognitionreactiontime;

MRT,motorreact iontime;

TRT,totalreactiontime



different psychophysiological responses of subjectswith ALDH2�1/�2 are more sensitive to the samedose of alcohol than those of subjects withALDH2�1/�1, it has been maintained that subjectswith ALDH2�1/�2 have a higher acetaldehydeconcentration in their blood (Agarwal and Goedde,1990; Higuchi et al., 1992; Chao, 1995). In thisstudy, although the BACs of both groups wereequivalent, there were significant differences withrespect to various objective and subjectiveresponses. Therefore, future studies should measurethe blood acetaldehyde concentration while evalu-ating various aspects of the acute effects of alcoholon psychobehavioral functions, including a range ofcognitive domains, such as attention, memory,learning, and executive function.

Since subjects with ALDH2�1/�2 have moreunfavorable psychobehavioral effects after alcoholingestion than subjects with ALDH2�1/�1, it isexpected that they will lower their levels of habitualdrinking over time and be less likely to developalcohol-related diseases. Therefore, these resultssuggest that the genetic polymorphism of ALDH2may affect drinking patterns and that it may be apredictive factor for alcohol overuse or abuse.

REFERENCES

Adachi J, Mizoi Y, Fukunaga T, Ogawa Y, Ueno Y, Imamichi H.1991. Degrees of alcohol intoxication in 117 hospitalized cases. JStud Alcohol 52: 448–453.

Agarwal DP, Goedde HW. 1990. Alcohol metabolism, alcoholintolerance, and alcoholism. Springer–Verlag: Berlin.

Campbell KB, Lowick BM. 1987. Ethanol and event-related poten-tials: the influence of distractor stimuli. Alcohol 4: 257–263.

Chao HM. 1995. Alcohol and the mystique of flushing (comment).Alcohol Clin Exp Res 19: 104–109.

Crabb DW, Edenberg HJ, Bosron WF, Li TK. 1989. Genotypes foraldehyde dehydrogenase deficiency and alcohol sensitivity: theinactive ALDH2 allele is dominant. J Clin Invest 83: 314–316.

Fagan D, Tiplady B, Scott DB. 1987. Effects of ethanol on psy-chomotor performance. Br J Anaesth 59: 961–965.

Goedde HW, Agarwal DP, Harada S. 1979. Racial differences inalcohol sensitivity: a new hypothesis. Hum Genet 51: 331–334.

Goedde HW, Agarwal DP, Harada S, et al. 1983. Population geneticstudies on aldehyde dehydrogenase isozyme deficiency and alco-hol sensitivity. Am J Hum Genet 35: 769–772.

Goedde HW, Singh S, Agarwal DP, Fritze G, Paik YK. 1989.Genotyping of mitochondrial aldehyde dehydrogenase usingoligonucleotide in South Korean blood samples: comparison withphenotyping in hair roots. Hum Genet 81: 305–307.

Harada S, Zhang S. 1993. New strategy for detection of ALDH2mutant. Alcohol 28(S1A): 11–13.

Higuchi S, Muramatsu T, Shogemori K, et al. 1992. The relationshipbetween low Km aldehyde dehydrogenase phenotype and drink-ing behavior in Japanese. J Stud Alcohol 53: 170–175.

Hindmarch I. 1982. Critical flicker fusion frequency (CFF): theeffects of psychotropic compounds. Pharmacopsychiatrica15(Suppl. 1): 44–48.

Hindmarch I, Aufdembrinke B, Ott H. 1988. Psychopharmacologyand reaction time. John Wiley & Sons, Ltd.: New York.

Hindmarch I, Shillingford J, Shillingford C. 1990. The effects ofsertraline on psychomotor performance in elderly volunteers. JClin Psychiatry 51(Suppl. B): 34–36.

Hindmarch I, Kerr JS, Sherwood N. 1991. The effects of alcohol andother drugs on psychomotor performance and cognitive function.Alcohol 26: 71–79.

Hsu LC, Bendel RE, Yoshida A. 1987. Direct detection of usual andatypical alleles on the human aldehyde dehydrogenases-2(ALDH2) locus. Am J Hum Genet 41: 996–1001.

Kim HJ, Park JS, Lee WJ, Choo YE. 1985. Blood ethanol curveanalysis and characteristics of circulatory function in men whoshow facial flushing after drinking. J Korean Med Assoc 28:1009–1024.

KimYH, Kim JH, Kim JS, et al. 1989.Manual for Korean version ofMinnesota Multiphasic Personality Inventory. Korea Guidance:Seoul.

Table 3. Results of repeated measures ANOVAs for P300 and psychomotor performance

P300 Psychomotor performance

Latency Amplitude

CFFT

CRT

DSSTFz Cz Pz Fz Cz Pz RRT MRT TRT

Time 17.78c 67.52c 821.03c 25.57c 119.93c 92.28c 0.44 26.24c 0.49 38.33c 11.81b

Drug 140.18c 7.14a 168.43c 5.37a 4.29 5.66a 0.01 12.50b 8.92b 1.90 8.36b

Group 0.82 1.30 54.55c 0.16 0.01 0.00 0.01 12.50b 8.92b 1.90 8.36b

Time�Drug 179.44c 34.84c 834.43c 2.47 11.30b 8.61b 0.31 4.47c 0.33 3.36 0.60Time�Group 4.86a 18.79 1466.96c 0.98 0.27 1.40 15.42b 1.86 12.75b 25.72c 21.37c

Drug�Group 27.06c 1.57 205.97c 3.32 3.67 4.32a 1.28 3.31 0.15 3.62 0.51Time�Drug�Group 57.65c 17.05c 995.25c 4.46a 1.30 1.44 10.73b 2.30 6.42b 14.06b 7.73b

Data are F values. Fz, frontal lead; Cz, central; Pz, parietal; CFFT, critical flicker fusion threshold; CRT, choice reaction time; RRT,recognition reaction time; MRT, motor reaction time; TRT, total reaction time; DSST, digit symbol substitution test.ap< 0.05; bp< 0.01; cp< 0.001.



Kim JM, Stewart R, Shin IS, Jung JS, Yoon JS. 2004. Assessment ofassociation between mitochondrial aldehyde dehydrogenasepolymorphism and Alzheimer’s disease in an older Korean popu-lation. Neurobiol Aging 25: 295–301.

Lawrence NW, Herbert M, Jeffcoate WJ. 1983. Circadian variationin effects of ethanol in man. Pharmacol Biochem Behav18(Suppl.): 555–558.

Michel C, Battig K. 1989. Separate and combined psychophysio-logical effects of cigarette smoking and alcohol consumption.Psychopharmacology 97: 65–73.

Mizoi Y, Ijiri Y, Tatsuno Y, et al. 1979. Relationship between facialflushing and blood acetaldehyde levels after alcohol intake.Pharmacol Biochem Behav 10: 303–311.

Mizoi Y, Tatsuno Y, Adachi J. 1983. Alcohol sensitivity related topolymorphism of alcohol-metabolizing enzymes in Japanese.Pharmacol Biochem Behav 18: 127–133.

Nishimura FT, Fukunaga T, Nishijo H, Ono T, Kajiura H,Yokomukai Y. 2001. Electroencephalogram spectral characteris-tics after alcohol ingestion in Japanese men with aldehydedehydrogenase-2 genetic variations: comparison with peripheralchanges. Alcohol Clin Exp Res 25: 1030–1036.

Ohmori T, Kayama T, Chen C, Yeh E, Reyes BJr, Yamashita I. 1986.The role of aldehyde dehydrogenase isozyme variance in alcoholsensitivity, drinking habits formation and the development ofalcoholism in Japan, Taiwan and the Philippines. Prog Neurop-sychopharmacol Biol Psychiatry 10: 229–235.

Palva ES, Linnoila M, Saario I, Mattila MJ. 1979. Acute andsubacute effects of diazepam on psychomotor skills: interactionwith alcohol. Acta Pharmacol Toxicol 45: 257–264.

Polich J, Kok A. 1995. Cognitive and biological determinants ofP300: an integrative review. Biol Psychol 41: 103–146.

Pollock VE, Teasdale TW, Gabrielli WF, Knop J. 1986. Subjectiveand objective measures of response to alcohol among young menat risk for alcoholism. J Stud Alcohol 47: 297–304.

Schuckit MA. 1984. Subjective responses to alcohol in sons ofalcoholics and control subjects. Arch Gen Psychiatry 41: 879–884.

Selzer ML. 1971. The Michigan Alcoholism Screening Test: thequest for a new diagnostic instrument. Am J Psychiatry 127:1653–1658.

Spielberger CD, Gorsuch RL, Lushene RE. 1970. Manual for theState-Trait Anxiety Inventory. Consulting Psychologist Press: PaloAlto.

Takeshita T, Yang X, Morimoto K. 2001. Association of the ADH2genotypes with skin responses after ethanol exposure in Japanesemale university students. Alcohol Clin Exp Res 25: 1264–1269.

Thomasson HR, Edenberg HJ, Crabb DW, et al. 1991. Alcohol andaldehyde dehydrogenase genotypes and alcoholism in Chinesemen. Am J Hum Genet 48: 677–681.

Wall TL, Ehlers CL. 1995. Acute effects of alcohol on P300 inAsians with different ALDH2 genotypes. Alcohol Clin Exp Res19: 617–622.

Wolff PH. 1972. Ethnic differences in alcoholic sensitivity. Science175: 449–450.

YokoyamaA,Muramatsu T, Ohmori T, Kumagai Y, Higuchi S, Ishii H.1997. Reliability of a flushing questionnaire and the ethanolpatch test in screening for inactive aldehyde dehydrogenase-2and alcohol-related cancer risk. Cancer Epidemiol Biomark 6:1105–1107.

Yoon BH, Yoon JS. 1996. Effects of alcohol on psychomotorperformance and subjective assessments in normal adults withvariation of acetaldehyde dehydrogenase I. J Korean Soc BiolPsychiatry 3: 222–239.

Yoon JS, Shin SH, Kook SH, Lee HY. 1997. A preliminary study on theKorean Translation of Composite Scale (KTCS) to measure morn-ingness-eveningness. J Korean Neuropsychiatr Assoc 36: 122–134.

Yoshida A. 1993. Genetic polymorphisms of alcohol-metabolizingenzymes related to alcohol sensitivity and alcoholic diseases. InPsychopharmacology and Psychobiology of Ethnicity, Lin KM,Poland RE, Nakasaki G (eds). American Psychiatric Press, Inc.:Washington, DC, 169–183.

Yum TH, Park YS, Oh KJ, Kim JG, Lee YH. 1992. Manual for theKorean Wechsler Adult Intelligence Scale K-WAIS. Korea Gui-dance: Seoul.



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