Correlates of increased risk for alcoholism in young men

Prog. Neuro-Psychophormocol. @ Biol. Psychiot. Printed in Great Britain. All rights reserved.

1986, Vol. 10, pp. 211-218 Copyright

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CORRELATES OF INCREASED RISK FOR ALCOHOLISM IN YOUNG MEN

SEAN O'CONNOR, Department

VICTOR HESSELBROCK

AND ALLAN TASMAN

of Psychiatry, University of Connecticut Farmington, Connecticut, U.S.A.

(Final form, December

Health

Center,

1985)

Abstract O'Connor, Sean J., Victor alcoholism in young men. 1. 2. 3. 4.

5.

Hesselbrock and Allan Tasman: Correlates of increased risk for Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1986, E(2):211-218.

Healthy men, aged 21-28, were divided into two groups according to the DSM-III diagnosis of alcoholism in their biological fathers. Evoked potentials from each subject were measured according to a visual odd-ball paradigm designed to elicit large responses in the midline parietal, Pz, lead. Subjects with alcoholic fathers produced significantly smaller amplitudes of the P3 component compared to subjects with non-alcoholic fathers. Reaction time, task difficulty and subject drinking history did not distinguish the groups. Subject's drinking history was not related to P3 amplitude.

Keywords:

alcoholism,

drinking

history,

ERP, genetic

risk, P3 amplitude

Abbreviations: central lead (Cz), electroencephalography (EEG), evoked potential (ERP), family history research diagnostic criteria (FH-RDC), frontal lead (Fz), monoamine oxidase activity (MAO), National Institute of Mental Health Diagnostic Interview Schedule (NIMH-DIS), negative peak 1 to positive peak 2 (Nl-P2), parietal lead (Pz), principal components analysis (PCA), temporal lead-left (T5), temporal lead-right (T6).

Introduction Alcoholism is a familial disorder (Cotton, 1979) and there is considerable evidence to suggest a genetic component of transmission from parent to offspring, at least in males. Studies of monozygotic and dizygotic twins (Kaij, 1960) adoption studies (Goodwin et al., 1973; Goodwin et al., 1977; Goodwin et al., 1974), family studies (Cloninger & Reich, 1983) and studies of half siblings (Schuckit et al., 1972) indicate that having an alcoholic parent substantially increases the risk for developing alcoholism in the offspring. For males, the increase in risk is about fourfold (Goodwin, 1985). Many factors that could be associated with inherited vulnerability have been studied. MAO activity (Hesselbrock et al., 1983; Schuckit et al., 1982) ethanol metabolism and acetaldehyde production and elimination (Hesselbrock & Shaskan, 1985; Schuckit & Rayes, 1979), color blindness (Cruz-Coke & Varela, 1965), ABO blood groups (Hill et al., 1975) and taste sensitivity for solutions of phenylthioureas (Swinson, 1973) have been examined in relation to alcoholism and its transmission to future generations. In general, however, no clear direction has been indicated by the findings. One area of investigation that has shown some promise for identifying a vulnerability factor has been the study of central nervous system functioning. There is increasing evidence that chronic alcohol abuse places an individual at risk for incurrino cerebral oatholoov. Radiological (Carlen & Wilkenson, 1980), neuropsychological (Ryan & Butters, 1983) and-" electrophysiological (Coger et al., 1978) data indicate that a significant proportion of

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sober alcoholics manifest some type of brain dysfunction. More important, there is some indication that the problems identified in alcoholics may have been present prior to the onset of alcohol use and may be present in non-alcoholic persons with an alcoholic parent (i.e. high risk individuals) to a degree that may differentiate them, at least as a group, from those without an alcoholic parent. Thus, certain aspects of brain function, not necessarily deficits or clinically apparent dysfunctions, may serve as vulnerability factors for the later development of alcoholism. Electrophysiological measures of brain function employ frequency domain analyses for electroenceohalosraohv (EEG) and time domain analvses for evoked ootential (ERP) data. EEG data reported this far on persons at high risk foi alcoholism are'equivocal: The increased activity in the beta band of the resting EEG of offspring with increased risk found in one study, (Gabrielli et al., 1982), could not be replicated-in a study on an older high risk samole, (Pollock et al.. 1983). Pollock et al.. (1983) indicated that bilateral beta svmmetry was a feature of increased risk in the hi~h.risk.group. Other studies (Volavka etal. 1985) of the spectral characteristics of the EEG suggest that reduced power in the lower half of the alpha band at the frontal lead locations in sober high risk subjects which increases after mild intoxication to levels similar to those found in controls may connote a vulnerability factor. However, markedly different methodology and technology make these and other EEG studies difficult to compare. Evoked potential data reflect a similarly wide range of methodology and technology. Age and drinking history of the cohort, stimulus modality, experimental paradigm and analytical technique are major variables that influence any results concerning the contribution of genetic factors in risk assessment. While auditory brain stem ERPs (Chu et al., 1978) and the Nl-P2 components from auditory and visual stimuli (Rhodes et al., 1975) show changes with alcoholization and abstinence after chronic abuse, it is with the long latency (ZOO600 msec) visually evoked, parietally dominant, attention sensitive component (P3) that evidence for an inherited vulnerability is emerging. A reduction in the amplitude of this c~ponent (a) has been found with acute intoxication in social drinkers, (b) worsens with chronic alcohol abuse, (c) persists after abstinence in alcoholics, but also (d) exists in a group of preadolescent non-drinking males at high familial risk. The present study sought to extend these results to an age group where social drinking has begun, yet abusive patterns have not. A reduced P3 amplitude in sober high risk subjects would support the notion of P3 as one electrophysiological marker of increased genetic risk. A replication of the experimental paradigm and analytic technique used by Begleiter et al., (1984) was chosen to minimize the influence of these variables on the experimental results.

Methods The sample consisted of young adult Caucasian males between 21 and 28 years of ,g;ubj~ts. ne group, the "High Risk" sample, contained 24 men recruited from a prospective The young men recruited for the present study were the study of children of alcoholics. Further, both paroffspring of a biological, alcoholic father and a non-alcoholic mother. ents and the subject were free of other major psychopathology. A comparison group of 26 young men were recruited from the outpatient dental clinics of the University of Connecticut Health Center. Neither the subjects, nor either parent, nor any biological second degree relative of this "Low Risk" comparison group, had ever met criteria for alcoholism. Both parents and the subject were also free of other major psychopathology. Data were collected between December 1984 and July 1985. Screening Battery. Screening data collected from each subject included demography, neuropsychological functioning and drinking/drug abuse information. A psychiatric screening interview, the NIMH-DIS, was used to obtain a complete and detailed psychiatric history from The psychiatric status of first and second degree bioeach subject (Robins et al., 1981). logical relatives was obtained from each subject using the history method developed by Family history-RDC criteria were used to diagnose family members Andreasen et al. (1977). All subjects were right handed. (Andreasen et al., 1977).

P3 in young males

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Procedure. Subjects were tested by personnel blind to the subject's group classification. Subjects were asked to abstain from all psychoactive substances for the 48 hours and from all-food and liquid (except for water) for the 8 hours prior to the experiment which began Sobriety was confirmed by breathalizer test, a standard breakfast was proat 8:00 a.m. vided, and lead placement and familiarization with the equipment was accomplished by 9:30 a.m. The data presented in this report were collected in the fifth of 24 blocks of data collection that spanned 2 l/2 hours in three states (sober, placebo, mild intoxication) and included three kinds of oaradiams (restinq EEG, visuallv evoked potentials, and autonomic The blocks that preceded the present study were calibration, resting EEG basearousal). The heads-task paradigm was not reline, autonomic baseline, and a separate ERP study. peated. The heads task paradigm is described in Begleiter et al. (1984), and is designed to yield ERPs in response to frequent, easy to interpret (non-target) stimuli, and to infrequent, No subject response was required for an oval nondifficult to interpret (target) stimuli. Target stimuli required the subject to identify which side of the head, target stimulus. left or right, was defined by adding one ear symbol and a nose symbol to the oval. Four target stimuli were included, each occurring with a probability of .0625; left and right Correct responses were defined by depressing only the ears for noses pointing up or down. appropriate "L" or "R" button within 1200 msec of a target stimulus onset. The order of stimulus presentation was determined by a computer generated Bernouli sequence. Each stimulus subtended a 3.3 arc centered about a fixation point on a video monitor placed at eye-level 1 meter away from the subject. Each stimulus lasted for 50 msec, and the interstimulus interval was uniformly distributed between 2.1 - 2.9 seconds. Monopolar derivations at Fz, Cz, Pz, T5, P3, P4 and T6, referenced to linked earlobes and a forehead ground were employed. Gold plated cup electrodes were pasted to cleansed scalp locations (Int lo-20 system) and electrode resistances were less than 5K ohms. Electrode potentials were amplified (50,000; .l, 100 Hz) and digitally sampled every 5 msec for the 150 msec before and 1350 msec after the stimulus onset. Trials contaminated by eye-blink artifact (trans-orbital electrodes) were sampled but not used in the averaging process. Collection proceeded until 50 artifact free, correct responses to the target stimuli were obtained. Raw data transients for each trial were sorted according to lead and stimulus difficulty, averaged, smoothed (3 point boxcar, 1 pass) and shifted so that the average in the prestimulus interval was zero. The resulting 28 ERPs (non-target), nose up ("easy"), nose down ("hard"), and all combined heads for each of 7 leads formed the analytical data base for this block of the experiment for each subject. Statistical Analysis. Several kinds of analysis were performed. Principal component Separate analyses (PCA) were used to reduce the number of variables in the ERP database. PCAs were used on the "easy heads" vs "ovals" and on the "hard heads" vs "ovals" ERPs for High and low Risk subjects. Since the resulting factor structures were nearly identical, the data were combined. A single PCA analysis using all leads, all subjects and all stimuli was conducted; the first four factors were selected for further analysis using the Screen test. A running t-test of the difference between groups (High and Low Risk) was performed for each kind of ERP (trial weighted grand mean data) for each lead in the analytical database.

Results The sample was divided into two groups. Subjects with an alcoholic biological father Offspring of non-alcoholic biological parwere classified as "High Risk" for alcoholism. ents were classified as being at "Low Risk" for alcoholism. Demographic

Characteristics

The High Risk and Low Risk groups were compared in terms of their age and level of education, two variables which may affect evoked potential measures. (Table 1). The High Risk sample was slightly older (diff=1.2 yrs. t=3.22, df=48, pc.05, while the Low Risk sample

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et al.

Table 1 Characteristicsof the two samples of young men

Risk group (N=24)

Controls (~=26)

Demograph Age Education Sex

25.3(+2,9) 15.04-(tZ.O) 100% ma‘res 0% females

23.1(+2.3)b 16.15T+1.3)b 100 % tiiales 0% females

l;.$$;)

13.30(+3.2) 0.55('T.5)

Drinking History Age first drink (years) Daily consumption (Avg)a

.

-*

a.0unces of absolute alcohol: computed from quantity and frequency of beer, wine, and liquor consumed in the past six months. bp<.05 Other No differences in frequency of consuming beer, wine, and liquor. No differences in frequency of drinking to mild intoxication (i.e. becoming "high") or in becoming drunk in the six months prior to testing had attended school longer (diff=l.2 yrs, t=2.31, dP48, pc.05). In both samples all subjects were males and all were right handed. Psychopathology A structured psychiatric interview, the NIMH-DIS, was used to assess current and past psychopathology in all subjects. Diagnoses were made according to DSM-III. Subjects were excluded from this study if there was any evidence of a past or present diagnosab?e psychiatric condition including alcohol or drug abuse. Drinking History_ A detailed assessment of each subject's drinking history revealed that both groups were similar in terms of the age of their first drink (t=.26, df=48, p=n.s.), and in their average daily consumption of ethanol (t=.98, df=48, p=n.s.), Table 1. Because a later section of the experiment, not reported here, involved an ethanol challenge, none of the subjects was a non-drinker. Examination of the quantity and frequency of usual consumption of beer, wine and distilled liquor revealed no significant group differences. Further, there were no significant differences in the reported frequency of drinking to mild intoxication (X2 = 2.89, df=5, p=n.s.) or in becoming drunk in the six months prior to testing (X2 = .98, df=5, p=n.s.). Evoked Potential Characteristics The four factors determined by PCA accounted for 87% of the coon variance in the ERP data and are shown in Fig. 1. Factor 1 is a rather broad c~ponent that flattens between

P3 in young

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males

Factor 1 . . .

Factor 4 -

Factor 3 ._. Factor 2 (P3)

Time (msec x 100)

Fig. 1. Factor loadings (PCA) of the first four factors for target and non-target stimuli for both groups. 625 and 825 msec before beginning to decline. Factor 2 is maximal at Pz and peaks at 375 msec. Factor 3 represents a biphasic component with a negative peak at 137 msec and a positive peak at 250 msec. The last component peaks at 310 msec and has a negative inflection at 475 msec. Factor 2, the P3 component, was examined further.

In the first analysis, the P3 component derived from all leads and across all artifact free correct responses to target stimuli was used for comparing the High and low Risk groups. It was found that the High Risk males had a lower amplitude on the P3 component than the Low Risk males (F=9.09, df=1,42, pc.05). Separate PCA analyses were conducted on the data collected at the Fz, Cz, and Pz leads. Differences in P3 amplitude were found between the High Risk and Low Risk subjects at Fz (F=8.94; df=1,39, pc.05) and at Pz (F=3.53; df=1,39, p<.069), but not at Cz (F=.O7; df=1,39. p=n.s.). For each lead examined the High Risk group had a lower amplitude than the Low Risk group. Since there is some controversy regarding the use of PCA analysis for ERP data (Hunt, 1985; Wood & McCarthy, 1984) an analysis of the grand mean data for the High and Low Risk groups was conducted. The High Risk group demonstrated a significantly smaller evoked potential amplitude in response to target stimuli throughout the 305-490 msec post-stimulus interval in

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the P3, P4 and T6 leads, i.e. midline parietal and right parieto-temporalregions (df=39, tXz.22; pc.05). No significant differences were found in the left parieto-temporalleads. Responses to non-target stimuli did not distinguish the two groups. 8ased on the reaction times (see below). there was reason to believe that "hard" {nose down) target stimuli elicited responses later than "easy" targets. An examination of the associated ERP data using PCA and grand mean analyses failed to reveal any significant differences within or between High and Low Risk groups at any lead based on assumed task difficulty. Finally, tke reiationship of ethanol consumption to tke amplitude of P3 irlas examined. For the total sample, no correlation was found between the average number of ounces consumed daily and P3 amplitude (t-=-.12,p=n.s.). Reaction Time The reaction times required to correctfy identify difficult and easy target stimuli were examined between groups and within groups. It was found that the average reaction time to all target stimuli taken together did not differ between groups; High Risk mean = 826 msec, Low Risk mean = 815 msec ft=.Z?, p=n.s.f. However, both groups required significantlymore time to correctly identify which side of the head symbol:an ear was on if the nose was pointed down rather than up. The High Risk group averaged 874 msec for "hard" targets versus 834 msec for the "easy" set (tm3.11, df=18, p'.O5). The Low Risk group averaged 877 msec for the "hard" targets compared to 787 msec for the "easy" set (t=3.84, df=21, pc.05). Discussion Overview This study compared the amplitudes of visually evoked ERPs of two groups of young men at differential genetic risk for developing alcoholism. The two groups were equivalent in terms of their age, level of education and drinking history. The visual odd-ball paradigm reported by Begleiter ff984) was chosen in order to compare our results to those reported for a younger, non-drinking sample based on data collected under very similar conditions. The ERP data to target stimuli were subjected to PCA and grand mean analyses and between group comparisons were made on the basis of P3 component amplitude at three lead locations. It was found that the High Risk group of young men had a lower amplitude on the P3 component at Fz and Pz leads, but not at Ct. Between group comparison of the grand mean ERP data produced similar findings, but suggested a laterality effect in that the increased amplitude demonstrated by the Low Risk group was also apparent in the right par~eto-temporalleads. The average daily amount of ethanol consumed was not related to the ampljtude of the P3 component. Although there were significant within group differences in reaction time to difficult versus easy target stimuli, the High Risk and Low Risk group did not differ in reaction times to target stimuli. Risk Factor At least two other studies fElmasian et al., I982; Begleiter et al., 1984) have reported reduced P3 voltages in sons of alcoholic fathers compared to sons of non-alcoholic fathers. Begleiter et al. (1984) studied boys between the ages of 8 - 13 years, while Elmasian et al. studied college age men (21-26) using both an alcohol and non-alcohol protocol. The findings of the present study are consistent with both Begleiter et al. and Elmasian et al. (1982) and add further evidence that a reduced P3 amplitude may serve as a biological marker of vulnerability for alcoholism at the level of group risk. It is difficult to describe the differences in P3 amplitude found between sons of alcoholic fathers and sons of non-alcoholic fathers as a deficit until either its functional or its neuroanatomical significance has been clearly determined. It is quite likely that the hippocampus and the amygdala contribute to the P3 component of the ERP (Begleiter et al., 1984). Although P3 components have been related to memory function and to the subject's assessment of stimulus significance, there is little evidence to indicate that offspring of alcoholic

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parents have deficits of clinical significance in these areas. Differences in neuropsychological abilities between groups of high and low risk individuals have been reported by a number of investigators (Schaffer et al., 1984; Tarter et al., 1984), but the test values for the high risk group often fall within the normal range. Even though neither the functional nor the biological significance of P3 has been determined, this does not preclude the consideration of reduced P3 amplitude as a "marker" or as a vulnerability factor for the development of alcoholism or alcohol abuse. The finding of a reduced P3 amplitude in sons of alcoholic fathers has been demonstrated across a substantial range of ages, socioeconomic backgrounds and drinking histories by Begleiter et al. (1984), by Elmasian et al. (1982). Our laboratory supports this suggestion. We note that the demonstration of an association of a reduced P3 amplitude and membership in a High Risk group is insufficient for assessing individual risk. The one facet of our study that might have been interpreted as supporting this idea was the examination of the relationship between the rate of recent drinking and degree of P3 amplitude reduction; we found no correlation. Although, as in Begleiter's sample of younger males, there was a clearly identifiable subset of the High Risk group that accounted for most of the reduction in the group's P3 average, there is no basis in our study for pointing towards a proportionately increased risk for these individuals. Longitudinal prospective studies would be useful in examining this possibility. Conclusion We conclude that neuroelectric activity associated with the response to novel, re'levant visual stimuli (ERP) provides a basis for distinguishing groups of healthy young men at differential genetic risk for alcoholism who drink in moderation.

This work was supported in part by a grant from the Heublein Corporation and NIAAA Grant 62P50AA03510. The authors would also like to thank Henri Beoleiter, Ph.D. for his helpful discussions of this project and Nancy DePalma and Karen Szymanski for their help in data collection and analyses. References ANDREASEN, N.C., ENDICOTT, J., SPITZER, R.L. and WINOKUR, G. (1977) The family history method using diagnostic criteria. Arch. Gen. Psychiatry 34:1229-1235. BEGLEITER, H., PORJESZ, B., BIHARI, B. and KISSIN, B. (f984rEvent-related brain potentials in boys at risk for alcoholism. Science =:1493-1496. CARLEN, P.L. and WILKINSON, D.A. (1980) Alcoholic brain damage and reversible deficits. Acta Psychiatr. Stand. 62 (Suppl. 286):103-118. CHU, N.S., SQUIRES, K.C. %d STARR, A. (1978) Auditory brain stem potentials in chronic alcohol intoxication and alcohol withdrawal. Arch. Neural. %:596. CLONINGER, C. and REICH, T. (1983) Genetic heterogeneity in alcoholism and sociopathy. In: Genetics of Neurological and Psychiatric Disorders, S. Kety, L. Rowland, R. Sidman and S. Matthysse (eds), pp. 145-166. Raven Press, New York. COGER, R.W., DYMOND, A.M., SERAFETINIDES,E., LOWENSTAM, I. and PEARSON, D. (1978) EEG Signs of brain impairment in alcoholism. Biol. Psychiatry 13(6):729-739. COTTON, N. (1979) The familial incidence of alcoho1ism.J. Stud. Alcohol 40:89-116. CRUZ-COKE. R. and VARELA, A. (1965) Inheritance of alcoholism: Its associason with color ’ blindness. Lancet 2_:1348.. ELMASIAN, R., NEVILLE, H., WOODS, D., SCHUCKIT, M. and BLOOM, F. (1982) Event-related brain potentials are different in individuals at high and low risk for developing alcoholism. Proc. Natl. Acad. Sci. 79_:7900-7903. GABRIELLI, W.F., MEDNICK, S.A., VOLAV~, J., POLLOCK,.V.E.,SCHULSINGER, F. and ITIL, T.M. ~~~8~~7ElectroencephaIogramsin children of alcoholic fathers. PsychophysiologyE:(4): .

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GOODWIN, D.W. (1985) Alcoholism and genetics. Arch. Gen. Psychiatry 42:171-174. GOODWIN, D., SCHLILSINGER, F., HERMANSEN, L., GUZE, S. and WINOKUR, G.71973) Alcohol problems in adoptees raised apart from alcoholic biological parents. Arch. Gen. Psychiatry 28:238-243. GOmWIN, D., SCHULSINGER, F., KNOP, J., MEDNICK, S. and GUZE, S. (1977) Alcoholism and depression in adopted-out daughters of alcoholics. Arch. Gen. Psychiatry 34:751-755. GOODWIN, D., SCHULSINGER, F., MOLLER, N., HERMANSEN, L., WINOKUR, G. and GEE, S. (1974) Drinking problems in adopted and nonadopted sons of alcoholics. Arch. Gen. Psychiatry 31:164-169. HEEELBROCK, V.M. and SHASKAN, E.G. (1985) Endogenous breath acetaldehyde levels among alcoholic and nonalcoholic probands. Progress in Neuro-Psychopharmacology 9(3):259-265. HESSELBROCK, V.M., SHASKAN, E.G. and MEYER, R.E. (1983) Biological/genetic Factors in alcoholism. NIAAA Research Monograph #9, Washington, D.C., NIAAA. HILL, S.Y., GOODWIN, D.W., CADORET, R., et al. (1975) Association and linkage between alcoholism and eleven serological markers. J. Stud. Alcohol 36(7):981-992. HUNT, E. (1985) Mathematical models of the event related potential. Psychophysiology -22 (4):395-402. Almquist & Wiksell, Stockholm. KAIJ, L. (1960) Alcoholism in Twins. POLLOCK, V.E.,.VOLAVKJX J., GOODWIN, D.W.; MEDNICK, S.A., GABRIELLI, W.F., KNOP, J. and SCHULSINGER. F. (1983) The EEG after alcohol administration in men at risk for alcoholism. Arch..Gen.'Psychiatry 40:857-861. D. (1975) Effect of alcohol and task on hemispheric RHODES, L.E., OBITZ, F.W. and mEEL, asyrrmetry of visually evoked potentials on man. Electroencephalogr. Clin. Neurophysiol. 38:561-568. ROmNS, L.N., HELZER, J.E., CROUGHAN, J. and RATCLIFF, K.S. (1981) NIMH Diagnostic Interview Schedule. Arch Gen. Psychiatry 38:381-389. ROBINS, L.N., HELZER, J.E., WEISSMAN, MX. ORVASCHEL, H., GRUENBERG, E., BURKE, J.D. and REGIER, D.A. (1984) Lifetime prevalence of specific psychiatric disorders in three sites. Arch. Gen. Psychiatry 41:949-958. RYAN, C. and BUTTERS, M.71983) Cognitive deficits in alcoholics. In: B. Kissin and H. Begleiter (eds), pp 485-538. Plenum Press, New York. differences between SCHAEFFER, K., PARSONS, 0. and YOHMAN, J. (1984) Neuropsychological male familial and nonfamilial alcoholics and nonalcoholics. Alcoholism: Clin. & Exp. Rsh. 8:347-351. Differences in blood acetaldehyde conSCHUCKIT, M. and RAYES, V. (1979) Ethanol ingestion: centrations in relatives of alcoholics and controls. Science 203:54-55. -. SCHUCKIT, M., GOODWIN, D. and WINOKUR, G. (1972) A study of alcoholism in half siblings. Amer. J. Psychiatry B:1132-1136. SCHUCKIT, M., SHASKAN, E., DUBY, J., VEGA, R. and MOSS, M. (1982) Platelet monoamine oxidase activity in relatives of alcoholics. Arch. Gen. Psychiatry 39:137-140. SWINSON, R.P. (1973) Phenylthiocarbamide taste sensitivity in alcoholism. Br. Med. J. @: 33-36. TARTER, R.E., HEGEDUS, A.M., GOLDSTEIN, G., SHELLEY, C. and ACTERMAN, A. (1984) Adolescent Neuropsychology and personality characteristics. Ale: Clin. & Exp. sons of alcoholics: Rsh. 8(2):216-222. VOLAVKA; J., POLLOCK, V., GABRIELLI, W.F. and MEDNICK, S.A. (1985) The EEG in persons at In: Recent Developments in Alcoholism, M. Galanter (ed), pp 21-36, risk for alcoholism. Vol. 3. Plenum Press, New York. WOOD, C.C. and MCCARTHY, G. (1984) Principal component analySiS of event-related potentials. Electroencephalogr. and Clin. Neurophysiol. -59:249-260. Inquiries

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