Event-related potentials in women at risk for alcoholism

Alcohol. Vol. 10, pp. 349-354, 1993 0741-8329/93 $6.00 + .00 Printed in the U.S.A. All fights reserved. Copyright © 1993 Pergamon Press Ltd.

Event-Related Potentials in Women at Risk

for Alcoholism

S H I R L E Y Y. H I L L *l A N D S T U A R T R. S T E I N H A U E R * t

*University o f Pittsburgh School o f Medicine, Department o f Psychiatry, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213

t Biometrics Research, 151R, Department o f Veterans Affairs Medical Center, Highland Drive, Pittsburgh, Pennsylvania 15206

Received 14 J a n u a r y 1993; A c c e p t e d 2 A p r i l 1993

HILL, S. Y. AND S. R. STEINHAUER. Event-related potentials in women at risk for alcoholism. ALCOHOL 10(5) 349-354, 1993.-Event-related potentials (ERPs) elicited during information processing tasks are useful for assessing brain function. Abstinent male alcoholics exhibit deficits in ERPs. The present study found that female alcoholics with early onset alcoholism (18.3 + 1.3 years) showed significant deficits in P300 amplitude relative to both high-risk and low-risk controls. Two interpretations of these findings are possible. P300 amplitude reduction among the alcoholic women might be a neuropathological consequence of excessive drinking. Alternatively, lower amplitude of the P300 wave may be a marker for alcoholism risk segregating within high-risk families and associated with development of alcoholism. The later interpretation is favored based on the unlikely possibility that the nonalcoholic high-risk women would later convert to alcoholic status due to their age (mean age of 35.6 + 1.6 years).

High-risk Women Alcoholism P300 Relatives of alcoholics Genetic factors Brain waves

Event-related potentials

RISK for developing alcoholism tends to be familial (3,9,13). Among men, some of the variance in risk has been presumed to be genetic, based on adoption (7) and twin studies (8,15, 16,18,24). Some have concluded that there is stronger evidence for a genetic basis in men than in women (6). A recent review of a number of twin, adoption, and family studies has con- eluded that while the evidence for a genetic basis for alcoholism in women is equivocal in some studies, there is just as much evidence in support of genetic mediation (10). There- fore, the recent report from a large scale twin study of women showing that over 50e/e of the variance in alcoholism risk in women can be explained by genetic factors is quite important (17). Finding markers of alcoholism risk that are minimally affected by environmental factors (e.g., exposure to an alcoholic parent, sibling, or other family member) could prove useful in understanding the relative contribution of genetic factors to alcoholism vulnerability. Additionally, these markers could be utilized in prevention efforts by providing a screen for alcoholism susceptibility.

Event-related brain potentials (ERPs) recorded at the scalp may provide one biological tool for accomplishing this goal. The ERP is of interest for two reasons. First, ERPs are associated with particular sensory and cognitive aspects of informa-

tion processing. Second, the ERP waveform appears to be under genetic control (2,25,30,31).

ERP studies in chronic alcoholics (22,26) and in individuals presumed to be at high risk for alcoholism (1,4,11,12,29) have demonstrated deficits in the P300 component utilizing information processing paradigms. However, previous investigations have found the deficit in alcoholic men, high-risk boys, or high-risk young men only.

Few studies have examined the P300 component o f the ERP in alcoholic women, and to our knowledge no one has looked at the high-risk relatives of alcoholic women for possible biological alteration. Parsons et al. (20) compared ERP characteristics in 67 female alcoholics and 49 female controls utilizing both an auditory and visual "oddball" paradigm (high and low tones/red and green circles), but were unable to find any differences in amplitude or latency between the alcoholics and the controls on any of the ERP variables assessed (NI00, N200, and P300). Additionally, these investigators contrasted family history positive (FHP) and family history negative (FHN) female alcoholics to determine if familial loading combined with alcoholism resulted in significant differences in ERP characteristics. Again, there were no differences. The present report reexamined the question of whether or not alco-

I To whom requests for reprints should be addressed.

349

350 HILL AND STEINHAUER

holic women, like alcoholic men, show a reduction in P300 amplitude and, additionally, examined the effect in their high- risk sisters.

METHODS

Alcoholic women, their high-risk sisters, and control women from low-risk families were evaluated for possible ERP differences. The alcoholic women and their high-risk sisters came from families with substantially elevated risk for developing alcoholism. Previous analyses of ERP data from these families have been reported for adult males and their parents (13,30) and their children (11,12,29). The high-risk families were part of one of two large scale family studies of alcoholism initiated in our laboratory (The Cognitive and Personality Factors Family Study [CPFFS] and Biological Risk Factors Family Study [BRFFS]). The former is concerned with pedigrees identified through male probands, and the lat- ter with those identified through female probands. These family studies include multiple extended pedigrees with multi- generational alcoholism, largely uncontaminated by other psychopathology (all first-degree relatives were required to be free of Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. [DSM-III] Axis I disorders). It should be noted that DSM-III was in use at the time the study was initiated. These high-risk families had been, in most cases, ascertained through a proband set comprised of a pair of alcoholic siblings, or alternative selection based on a high density of alcoholism (minimum of two first-degree relatives of the proband with alcoholism). The presence of alcoholism or other psychopathology was determined for these sibling pairs and their first- degree relatives through face-to-face interviews (Diagnostic Interview Schedule [DIS]), allowing for DSM-III (28) and Feighner Criteria (5) to be applied.

The low-risk families, who were also part of the larger studies, included multiple members of pedigrees selected for absence of psychopathology. These families were selected from among volunteers who responded to advertisements in local newspapers soliciting participation in research. Families qualified for participation by having both multiple siblings and at least one parent available for personal interview, as well as absence of psychopathology, including alcoholism, upon direct interview (DIS). So that the structural characteristics of the two family types were similar, the families were selected either through a pair of normal male siblings or a pair of normal female siblings. All available siblings and parents were interviewed to confirm the absence of psychopathology in the designated sibling pair and their first-degree relatives.

SUBJECTS

We assessed 25 alcoholic women, 31 nonalcoholic sisters of these alcoholic women, and 30 control women. All of the alcoholic women met DSM-III criteria for alcohol dependence and Feighner Criteria (5) for definite alcoholism. None met criteria for drug dependence by DSM-III criteria. These women were characterized by a severe form of alcoholism with an early onset (the mean age at onset of the first Fcighner Criteria problem was 18.32:1:1.34 years). This was largely the result of a selection strategy that resulted in a particularly high density of alcoholism within the pedigrees from which the women were selected.

The control women did not meet Feighner Criteria for even probable alcoholism, or any Axis I DSM-III disorder. (DSM- III was the diagnostic system in place when the study was

initiated.) All of the women were in reasonably good health and were screened for absence of drug and alcohol use in the past 48 h. The mean ages (with standard error) of the three groups were 32.2 ± 1.3, 35.6 + 1.6, and 35.1 + 1.5 for the alcoholic women, their nonalcoholic sisters, and the controls, respectively. Similarly, they were well matched on socioeconomic status, with 75.907o of the low-risk and 55.4% of the high-risk women coming from the top two socioeconomic levels (socioeconomic status was calculated using Hollingshead's two-factor model [141). All women included in the present analyses were Caucasian.

To control for possible menstrual cycle effects, a determi- nation was made of menstrual cycle day by self-report and/or plasma progesterone levels (97°70 of the sample had one or both). Approximately 54°7o of the women were in the follicular phase, 26070 were in the luteal phase, and 20070 were not cy- cling.

pROCEDURE

Visual Paradigm

The task employed in this study was a visual ERP task after the procedure of Begleiter et al. (1). An Atari 130 computer executed a BASIC program to present the stimuli at a 33-ms duration with intertrial interval varying randomly between 2.25 and 4 s. The subjects were seated in a darkened, sound- attenuated testing room. Stimuli were displayed on a Magna- vox RGB Monitor 80 placed 132 cm from the subject, sub- tending a visual angle of 3.8 °. The monitor was set to the default green mode, resembling the oscilloscope display used by Begieiter et al. (1). Five stimuli were randomly presented. One view, the nontarget stimulus, was a simple circle to which the subject was instructed not to respond (blank condition). There were four possible aerial views of the target stimulus, a representation of a head with a nose and only one ear. The subject was instructed to press the button which corresponded to the depicted ear. The easy condition occurred when the nose was oriented upward and the ear (right or left) was on the same side as the button depressed. In the hard condition, the nose was oriented downward and the subject was required to spatially rotate the head in order to respond correctly. Thus, in the hard condition, the ear was depicted on the opposite side of the head as the button pressed.

A standard set of instructions was read to each subject. If additional clarification was needed, directions were amplified by the experimenter. The subject was first shown a picture of each of the stimuli and asked to make the correct response to each head (target) stimulus. Next, each stimulus was presented on the video monitor at a slow pace using a long exposure duration (3200 ms). Once the subject was performing correctly (usually less than 10 trials), the visual display duration was decreased to the 33-ms exposure time of the main experiment for several additional practice trials. (The subjects were en- couraged to respond quickly, but more importantly, to respond accurately.) Two blocks of 120 trials were presented to the subjects. Of the 240 total trials, 160 were blank (nontar- gets), 40 were easy condition targets (20 right, 20 left), and 40 were hard condition targets (20 right, 20 left).

Auditory Paradigm Each subject performed two tasks during which auditory

ERPs were recorded. Subjects were given an audioscope screening test of 40 dBHL at frequencies of 500, I000, 2000, and 4000 Hz. Results indicated that hearing was not impaired in any of the subjects.

ERPS IN WOMEN AT RISK FOR ALCOHOLISM 351

The experiments consisted of modifications of a typical oddball paradigm: a simple Counting task followed by a Choice Reaction task, both of which have been employed pre- viously in our laboratory (12,30). For both tasks, the subjects sat in a sound-attenuated, darkened room, and listened to "high-" (1500 Hz) and "low-pitched" (800 Hz) tones presented every 3 s through a speaker placed in front of the subject. Prior to testing, subjects were required to identify "high" and "low" tones to ensure pitch differentiation. Tones were 40 ms in duration with an abrupt (2 ms) rise and fall time, at an intensity of 70 dBA (Edmont-Wilson Sound Level Meter, Model 60-510). High and low tones were randomly generated by computer so that the overall probability of a high (infrequent) tone would be .25. The only restriction on the random tone sequence was that two high tones could not occur in succession.

All subjects were told at the onset of testing that 1) the first tone they would hear on each block of trials would be a low tone, 2) there would be fewer high tones than low tones, and 3) two high tones would never occur in a row. To be sure that the task was understood, each subject was asked which tone would be heard after a high tone. All subjects responded by correctly indicating that a low tone would follow. Thus, a low tone, when preceded by a high tone, was a totally predict- able event ("certain"), having a conditional probability of 1.00. After the occurrence of any low tone, either a high tone or another low tone could follow. Two low tones in succession, occurring on two thirds of these trials, carried a conditional probability of .67, while a high tone occurring after a low tone (rare event) occurred one third of the time (conditional probability of .33).

For the Counting task, the subject was asked to count silently the number of "high" (infrequent) tones heard, and to report the total at the end of the block. In the Choice Reaction task, subjects pressed one button when a high tone was heard and another button when a low tone occurred, alternating with each subject as to whether the left button first corresponded to a high tone or a low tone. On the second Choice Reaction block the subject was required to do the opposite. Responses were automatically encoded to determine accuracy.

For both the Counting and Choice Reaction tasks, subjects were asked to perform two blocks of 80 trials each. Each error-free block resulted in a reward of $0.25; $0.10 was given for each block with one or two errors (three e r r o r s - n o reward). Blocks with six or more errors were excluded from the analysis. All trials performed incorrectly during the Choice Reaction task were also discarded.

Event-related potentials were recorded using SensorMedic Ag/AgCI electrodes placed over the midline frontal, vertex, parietal, and occipital (Fz, Cz, Pz, Oz) locations, and left and right parietal (P3,P4) locations, referred to linked ears, with forehead ground. Ocular artifacts were monitored from an electrode placed beneath the left eye, referred to linked ears. All data were monitored on-line by an oscilloscope, and all trials affected by eye artifact (those exceeding approximately 50 ~tV) were coded for exclusion. Electrophysiological data were amplified by 20 000 (10 000 for the eye channel) using a Grass Model 12 Neurodata system, set to a bandpass of 0.01 to 30 I-Iz. For the visual paradigm, a Digital Equipment Cor- poration PDP-I 1/23 lab computer was slaved to coincide with the video output of the Atari. Data were digitized for 1200 ms at 125 Hz, beginning 200 ms prior to stimulus onset, by a PDP 11/23 computer system and stored on magnetic media. The subject's response, reaction time, and correctness of the response were automatically encoded into the data file.

Blinks or other artifacts exceeding approximately 75 ~tV were coded on-line, or detected automatically during off-line analysis. Artifact free trials for each task were averaged for each condition and electrode. At least two raters, blind to each subject's family history, identified the ERP components (NI00, P200, N250, and P300) off-line using an interactive peak detection algorithm which chose the maximal amplitude for a given component (at Cz for NI00, P200, and N250; at Pz for P300) within a predefined latency window (N100: 80- 136 ms; P200:136-240 ms; N250:200-320 ms; P300:264-424 ms). Components found outside the expected latency range were identified by consensus among raters, and the computer was adjusted to select this latency. Peak amplitude was com- puted as the deviation from the median voltage during the 200-ms prestimulus baseline, using the same time point for all electrode sites. Latency and amplitude data were automatically extracted and stored in ASCII files for subsequent analysis.

Behavioral and ERP data were analyzed utilizing analysis of variance (ANOVA) (BMDP2V). The Greenhouse-Geisser correction for non_homogeneity of variance was applied where appropriate. For post hoc comparisons, the Newman-Keuls test (alpha = .05) was employed.

RESULTS

Visual Findings

Behavioral Measures. Reaction time data were statistically analyzed using an ANOVA to determine possible behavioral differences between groups. If the groups were found to be equivalent behaviorally, then any differences observed between groups with respect to ERP characteristics would be especially salient. Behavioral differences due to task complex- ity (hard vs. easy) and the interaction of these variables were also evaluated. No significant differences between groups were found, indicating an equivalence in behavioral performance. A significant Condition effect was seen as a result of reaction times being longer for the hard than the easy condition, F(1, 83) = 220.63, p < .0001.

Performance was also analyzed in terms of hit rates for the combined target conditions and false alarm rates for the blank condition. Hit rates showed little variation between groups, with both nonalcoholic and alcoholic women showing rates of .90, and controls .91. No significant differences in false alarm rates between groups were seen (all were < .001). Thus, the behavioral data show a remarkable degree of similarity between groups, indicating that any differences seen in P300 could not be explained by differences in performance.

Overall Analysis-Amplitude of 1)300. An overall ANOVA was used to assess the independent effects of Group (high- or low-risk), Condition (hard, easy, and blank), and Electrode (Fz, Cz, Pz, P3, P4, and Oz) with respect to the amplitude of the ERP components. We found highly significant differences for each main effect.

Of particular importance to our notion that biological risk factors would be found among alcoholic women and their high-risk relatives, we found an overall Group effect, F(2, 83) = 8.83,p = .0003, for the P300 component across electrodes and conditions. Additionally, we found significant differences by Condition, F(2, 121) = 20.28, p < .0001. This was due to the fact that there was a smaller response to the blank condition in contrast to the hard and easy conditions, though there was no difference between hard and easy.

A main effect of Electrode site was found, F(5, 255) = 25.50, p < .0001. P300 showed its typical maximum for this


task at the midline parietal (Pz) site. Consequently, differences among the risk groups (alcoholic, nonalcoholic high-risk sisters, and low-risk controls) were evaluated within each condition at Pz. A one-way ANOVA with contrasts by Newman- Keuls procedure was performed for each condition separately. For the hard condition, the ANOVA, F(2, 83) = 7.07, p = .0015, revealed that the alcoholics were significantly different from controls and from their nonalcoholic high-risk sisters at p < .05 (Fig. 1). The mean amplitude for the alcoholics was smaller (9.56 #V + 1.6) than that found for their nonalcoholic sisters (17.48 #V + 1.4) and the low-risk controls (14.17 #V + 1.5).

Similarly, for the easy condition, F(2, 83) = 6.04, p = .0036, alcoholics differed from controls and from their nonalcoholic sisters (p < .05). The same pattern was observed for the blank condition, F(2, 83) = 6.20, p = .0031, with

P Z N100

A U D I T O R Y N250

P2OO "...,.....~e

Count ino

.33 condition

Cho ice Reac t ion

.33 condition

P Z

V I S U A L

Hord condition

P z

-10 #v --~

0 O

i , i I i

~ O O m s g c

- - Control - - - Non Alcoholic .." Alcoholic

FIG. 1. Grand mean ERPs were recorded in auditory and visual tasks. Onset and duration for the 40-ms auditory stimuli are indicated by the blackened rectangle beginning at time zero; visual stimuli had an offset at 33 ms. Data are presented for alcoholic women (dotted line) (N = 25), their nonalcoholic high-risk sisters (dashed line) (N = 31), and control women (solid line) (N = 30) for the infrequent condition of the auditory tasks and the hard condition of the visual task. P300, the large, positive (downward) deflection prominent at Pz at approximately 300 ms, is reduced in all conditions for the alcoholic w o m e n .

alcoholics differing from both normal controls and their high- risk sisters.

P300 Latency. A Group x Condition analysis of the latency of P300 at Pz indicated no significant differences among risk groups, F(2, 83) = 0.09, p = .91, but a significant difference by Condition in P300 latency, F(2, 135) = 14.98, p < .0001, due to longer latencies observed for the target versus the blank conditions. However, there was no significant interaction found between Group and Condition.

Earlier ERP Components-Amplitude. Asnplitude findings for earlier components are summarized briefly. An analysis was performed for Group x Condition x Electrode effects for the early components. Amplitudes of NI00, P200, and N250 all failed to show main effect differences by risk group. While significant differences in amplitude were noted by Condition (NI00 and P200) and by Electrode (P200 and N250, both largest at Cz), none of these effects were found to interact with risk group status and, therefore, are not reported here.

Earlier ERP Components-Latency. Analyses were performed for Group x Condition effects for the early components at Cz. No differences were found for either N100 or P200. While statistically significant differences by risk group were noted for N250, they fell within a range of only one or two sampling points (i.e., data were digitized only every 8 ms). For completeness, they are: Group, F(2, 83) = 5.13, p = .0079; Condition, F(2, 150) = 14.75, p < .0001; and Group x Condition, F(2, 150) = 2.74,p = .0359.

Auditory Findings Overall Analysia-P300 Amplitude. It was of interest to

determine if the risk status groups would differ, utilizing the auditory modality, as they had for the visual modality. Thus, an overall analysis was performed to determine the separate effects of Group (alcoholic, nonalcoholic, or control), Task (Counting or Choice Reaction task), Probability (.33, .67, and 1.00), and Electrode site upon amplitude. Significant differences by Group were found, F(2, 83) = 4.02, p = .0215, indicating that risk group status resulted in notable variations in P300 amplitude. Significant differences were also found by Task, F(1, 83) = 13.30, p = .0005; Probability, F(2, 135) = 329.30, p < .0001; and Electrode, F(2, 177) = 133.95, p = .0001. P300 was more positive in the Choice Reaction than in the Counting task, showed an increase in amplitude as conditional probability decreased (with significantly larger amplitudes in the .33 condition as compared to the .67 and 1.00 conditions), and was significantly larger at Pz than at other sites. There were no significant interactions between Group and any of the other main effects (Task and Probability). Significant interactions involving Electrode site and Task × Probability are not reported here.

In parallel with our analyses of the visual ERP data, we examined the response to each condition separately within each task. For the Counting task, one-way ANOVAs at Pz for each task were performed for each of the probability conditions (.33, .67, and 1.00), and the Newman-Keuls test utilized for comparison of the three groups. The condition in which P300 was largest (.33) revealed significant differences among the three groups, F(2, 83) = 3.67, p = .0296. P300 amplitude was significantly reduced for the alcoholic women compared to the controls and the nonalcoholic sisters of the alcoholics (Fig. 1). The mean amplitude for the alcoholic women was 12.81 pV + 1.1, and the nonalcoholic sisters were 16.34 #V + 1.1, whereas the controls were 17.05 /zV + 1.2.

ERPS IN WOMEN AT RISK FOR ALCOHOLISM 353

Similar results were obtained for the other auditory task (Choice Reaction task) when analyzed within the probability condition. The condition showing the largest P300 amplitude (.33 condition) revealed a significant difference, F(2, 83) = 3.85,p = .0251, with alcoholic women having smaller P300 amplitudes than their nonalcoholic sisters. One-way ANOVAs, performed for each probability condition separately, showed differences for the Choice Reaction task when the conditional probability of a target was less frequent (nontarget followed by a target). For the .33 condition of the Choice Reaction task, the alcoholics showed P300 amplitudes of 13.48/~V + 1.5, while their nonalcoholic sisters displayed amplitudes of 18.96 I~V + 1.2. In this particular task, alcoholics did not differ from controls, however (16.93 #V :1: 1.5).

P3OOLatency. Latency effects were analyzed at the Pz electrode, with no main effects of P300 latency being found among the risk groups. This absence of an overall latency difference among the groups reinforces the notion that group differences in P300 amplitude are not due to differences in exposure to alcohol. If this were the case, P300 latency differences among groups would most probably have been observed as well.

As typically observed in these paradigms, there was a significant increase in latency associated with decreasing event probability, F(2, 163) = 30.02, p < .0001. An important interaction between Probability and Group was found, F(4, 163) = 2.83, p = .0271. This was a result of longer latencies being observed in the "certain" condition (probability = 1.00) for the high-risk individuals (alcoholic and nonalcoholic alike) in contrast to the low-risk controls. Moreover, the rate of change in latency with increasing certainty was greater for controls than for the high-risk women. The control women responded to the changing probability condition by reducing their latency of response by 10.107o, the nonalcoholic sisters by 6.1070, and the alcoholic women by 3.5070.

Early Components-Amplitude. There were no main effects or interactions involving risk status for NI00, P200, or N250. Topographically, N100 and P200 were maximal at Cz, while N250 was most negative at Fz (for all main effects of Electrode,p < .0001). P200 was more positive for the Count- ing than for the Choice Reaction task,/7(1, 83) = 56.25, p < .0001, and was more positive for the 1.0 condition than the .33 and .67 conditions, F(2, 152) = 23.36, p < .0001. Similarly, N250 was less negative for the Counting than for the Choice Reaction task, F(1, 83) = 20.26, p < .0001. Other interactions involving electrode site are omitted.

Early Components--Latency. There were no significant differences over a range greater than 12 ms for NI00, P200, or N250, with one exception: N250 latency increased as conditional probability decreased, F(2, 152) = 77.25, p < .0001. As this is opposite to the finding for P300 latency, it indicates that P300 latency increments associated with decreasing probability cannot be accounted for by N250-associated effects.

P300 and Progesterone Levels. To insure that menstrual cycle effects did not contribute to the overall P300 differences observed between risk groups, correlations between progesterone and P300 amplitude were calculated. Nonsignificant correlations were found for visual tasks (r = .05) and for the auditory tasks (r = .12 and .08 for the Counting and Choice Reaction tasks, respectively), also indicating no appreciable effect of menstrual cycle on P300 amplitude.

DISCUSSION

The present results demonstrated substantial differences in the magnitude of the P300 component between women se-

lected on the basis of their familial risk for developing alcoholism. In the visual modality, an 8-/~V difference was observed between alcoholic women and controls, representing almost a 50% decrement in voltage for the alcoholic women. It is unlikely that the differences between groups could be the result of attentional differences, as reaction times did not differ between groups, nor did the accuracy of their responses as measured by hit rates. Moreover, the women were well matched on age and socioeconomic status, particularly in the case of alcoholic and nonalcoholic sisters. However, even the low-risk controls matched the high-risk sisters quite well. Finally, we evaluated menstrual cycle effects by obtain- ing self-reports of menstrual cycle day and plasma progesterone levels, concluding that menstrual cycle differences could not account for the differences observed between groups.

Decrements in P300 amplitude in abstinent chronic male alcoholics have frequently been reported (21,22,23,26). More- over, investigations of male alcoholics with prolonged absti- nence suggest that these decrements are not reversible (21,27). Therefore, it may be concluded that the reduction in P300 voltage observed in these chronic alcoholic women is not associated with acute alcohol exposure, but rather may well ante- date alcohol abuse. The nonalcoholic high-risk sisters appear to have escaped becoming alcoholic in association with higher P300 voltages, making them more similar to the low-risk women.

The significance of the alcoholic women showing reduced P300 amplitudes may be interpreted in two ways. It might be argued that chronic alcoholics, although abstinent for a considerable period of time before neurophysiological record- ing, may have suffered irreversible brain dysfunction, which the P300 amplitude reflects. Alternatively, it may be argued that P300 amplitude is relatively stable, even when an individ- ual experiences neuropathological changes-unlike P300 latency, which appears to reflect neuropathological insults and normal aging much better (19,23). Finally, recent studies have shown that young children never exposed to alcohol show reductions in P300 amplitude but not latency if they are from high-risk families (11,29,32).

In summary, the present findings provide the strongest evidence obtained to date that P300 amplitude reduction may be an important neurobiological marker of alcoholism risk in women. Differences between the high- and low-risk groups could not be attributed to differences in behavioral performance of the tasks, age, socioeconomic status, or menstrual cycle effects. Moreover, these differences in amplitude between groups were replicated across two different auditory tasks and a visual one. Analyses of earlier components (NI00, P200, N250) showed that the differences observed between the three groups of women were specific to P300 amplitude. In view of the recent report that as much as 50070 of the variance in outcome with regard to adult alcoholism can be attributed to genetic factors (17), these results hold promise for screening young girls to determine possible risk status. Com- pletion of longitudinal studies to fully assess this possibility are needed.

ACKNOWLEDGEMENTS

We thank J. Locke, S. Gronlund, and S. Lalney for their technical assistance, and T. Smith and D. Huska for recruiting subjects and assisting in the clinical evaluations. This research is supported by grants from the National Institute on Alcohol Abuse and Alcoholism AA05909 and AA08082.


REFERENCES

1. Begleiter, H.; Porjesz, B.; Bihari, B.; Kissin, B. Event-related brain potentials in boys at risk for alcoholism. Science 225:1493- 1496; 1984.

2. Bock, F. Pupillary dilation and vertex evoked potential similarity in monozygotic and dizTgotic twins and siblings. New York: City University of New York; 1976. Dissertation.

3. Cotton, N. S. The familial incidence of alcoholism. J. Stud. Alco- hol 40:89-116; 1979.

4. Elmasian, R.; Neville, H.; Woods, D.; Schuckit, M.; Bloom, F. Event-related brain potentials are different in individuals at high and low risk for developing alcoholism. Proc. Natl. Acad. Sci. U. S. A. 29:7900-7903; 1982.

5. Feighner, J. P.; Robins, E.; Guze, S. B.; Woodruff, R.; Wino- kur, G.; Munoz, R. Diagnostic criteria for use in psychiatric research. Arch. Gen. Psychiatry 26:57-63; 1972.

6. Gilligan, S. B.; Reich, T.; Cloninger, C. R. Etiologic heterogeneity in alcoholism. Genet. Epidemiol. 4:395-414; 1987.

7. Goodwin, D. W.; Sehulsinger, F.; Hermansen, L.; Guze, S. B.; Winokur, G. Alcohol problems in adoptees raised apart from alcoholic biological parents. Arch. Gen. Psychiatry 28:238-243; 1973.

8. Gurling, H. M. D.; Murray, R. M.; Clifford, C. A. Investigations into the genetics of alcohol dependence and into its effects on brain function. In: Gedda, L.; Parisi, P.; Nance, W. E., eds. Twin research 3: Epidemiological and clinical studies. New York: Alan R. Liss, Inc.; 1981:77-87.

9. Hill, S. Y.; Cloninger, C. R.; Ayre, F. R. Independent familial transmission of alcoholism and opiate abuse. Alcohol. Clin. Exp. Res. 1:335-342; 1977.

10. Hill, S. Y.; Smith, T. R. Evidence for genetic mediation of alcoholism in women. J. Subst. Abuse 3:159-174; 1991.

11. Hill, S. Y.; Steinhauer, S. R. Assessment of prepubertal and postpnhertal boys and girls at risk for developing alcoholism with P300 from a visual discrimination task. J. Stud. Alcohol; in press.

12. Hill, S. Y.; Steinhauer, S. R.; Park, J.; Zubin, J. Event-related potential characteristics in children of alcoholics from high density families. Alcohol. Clin. Exp. Res. 14:6-16; 1990.

13. Hill, S. Y.; Stei__nhauer, S. R.; Zubin, J. Biological markers for alcoholism: A vulnerability model conceptualization. In: Rivers, R. C., ed. Alcohol and addictive behavior, Nebraska symposium on motivation, 1986. Lincoln: University of Nebraska Press; 1987:207-256.

14. Hollingshead, A. B. Four factor index of social status. 1975. 15. Hrubec, Z.; Omenn, G. S. Evidence of genetic predisposition to

alcoholic cirrhosis and psychosis: Twin concordances for alcoholism and its biological end points by zygosity among male veterans. Alcohol. Clin. Exp. Res. 5:207-215; 1981.

16. Kaij, L. Studies on the etiology and sequels of abuse of alcohol.

In: Almqvist; Wikseil, eds. Alcoholism in twins. Stockholm: Uni- versity of Lund; 1960.

17. Kendler, K. S.; Heath, A. C.; Neale, M. C.; Kessler, R. C.; Eaves, L. J. A population-based twin study of alcoholic women. JAMA 14:1877-1882; 1992.

18. McGue, M.; Pickens, R. W.; Svikis, D, S. Sex and age effects on the inheritance of alcohol problems: A twin study. J. Abnorm. Psychol. 101:3-17; 1992.

19. Morrow, L. A.; Steinhauer, S. R.; Hodgson, M. J. Delay in P300 latency in patients with organic solvent exposure. Arch. Neurol. 49:315-320; 1992.

20. Parsons, O. A.; Sinha, R.; Williams, H. L. Relationships between neuropsychological test performance and event-related potentials in alcoholic and nonalcoholic samples. Alcohol. Clin. Exp. Res. 14:746-755; 1990.

21. Patterson, B. W.; Williams, H. L.; McLean, G. A.; Smith, L. T.; Sehaeffer, K. W. Alcoholism and family history of alcoholism: Effects on visual and auditory event-related potentials. Alcohol 4:265-274; 1987.

22. Pfefferbaum, A.; Horvath, T. B.; Roth, W. T.; Kopell, B. S. Event-related potential changes in chronic alcoholics. Elec- troencephalogr. Clin. Neurophysiol. 47:637-647; 1979.

23. Pfefferbaum, A.; Rosenhloom, M.; Ford, J. M. Late event- related potential changes in alcoholics. Alcohol 4:275-281; 1987.

24. Pickens, R. W.; Svikis, D. S.; McGue, M.; Lykken, D. T.; Hes- ton, L. L.; Clayton, P. J. Heterogeneity in the inheritance of alcoholism: A study of male and female twins. Arch. Gen. Psy- chiatry 48:19-28; 1991.

25. Polich, J.; Burns, T. P300 from identical twins. Neuropsycho- logia 25:299-304; 1987.

26. Porjesz, B.; Begieiter, H. Human evoked brain potentials and alcohol. Alcohol. Clin. Exp. Res. 5:304-317; 1981.

27. Porjesz, B.; Begieiter, H. Human brain electrophysiolngy and alcoholism. In: Tarter, R.; van Thiel, D., eds. Alcohol and the brain. New York: Plenum Press; 1985:139-182.

28. Spitzer, R. L. Diagnostic criteria from DSM-III, 3rd ed. Wash- ington, DC: American Psychiatric Association; 1982.

29. Steinhauer, S. R.; Hill, S. Y. Auditory event-related potentials in children at high risk for developing alcoholism. L Stud. Alcohol; in press.

30. Steinhauer, S. R.; Hill, S. Y.; Znhin, J. Event-related potentials in alcoholics and their first degree relatives. Alcohol 4:307-314; 1987.

31. Surwilio, W. W. Cortical evoked potentials in monozygotic twins and unrelated subjects: Comparisons of exogenous and endoge- nous components. Behav. Genet. 10:201-209; 1980.

32. Whipple, S.; Parker, E. S.; Noble, E. P. An atypical neurocogni- five prof'fle in alcoholic fathers and their sons. J. Stud. Alcohol 49:240-244; 1988.

Documents

Event-related potentials in women at risk for alcoholism