Alcohol, VIII. 8. pp. 219-222. o Pergamon Press plc, 1991. Printed in the U.S.A.
Familial Density of Alcoholism: Effects on Psychophysiological Responses to Ethanol M . E. M c C A U L , I j. S. T U R K K A N , D. S. S V I K I S A N D G. E. B I G E L O W
Behavioral Pharmacology Research Unit The Johns Hopkins Universit3, School o f Medicine Baltimore, M D 21224 R e c e i v e d 2 O c t o b e r 1990; A c c e p t e d 4 J a n u a r y 1991 McCAUL, M. E., J. S. TURKKAN, D. S. SVIKIS AND G. E. BIGELOW. Familial density of alcoholism: Effects on psychophysiological responses to ethanol. ALCOHOL 8(3) 219-222, 1991.--Recent research findings suggest that the patterning of familial alcoholism may critically determine ethanol sensitivity and severity of alcohol-related problems in the offspring. The present study examined the effects of familial alcoholism density on psychophysiological responses to ethanol administration in college males. Subjects with a positive family history of alcoholism were classified into affected biological father only (LD-FHP) versus both father and at least one second-degree affected relative (HD-FHP), and were compared to family history negative (FHN) subjects. Subjects received I g/kg ethanol or placebo in a double-blind procedure. A battery of subjective, physiological and psychomotor measures was collected once prior to and four times following drink administration. HD-FHP subjects showed significantly greater subjective effects, body sway and skin conductance after alcohol ingestion than either FHN or LD-FHP subjects; in contrast, there was no difference on any measure for LD-FHP versus FHN subjects. Our findings of increased ethanol sensitivity as. a function of familial density of alcoholism strongly suggest the importance of carefully defining family history characteristics in all studies examining potential markers or risk factors for alcoholism. Alcoholism
Familial density of alcoholism
Alcohol ingestion
RECENT findings from both epidemiological and laboratory research suggest that the patterning of familial alcoholism may be a critical determinant of sensitivity to ethanol effects and the severity of alcohol-related problems in the offspring (7, 17, 19, 20). In a recent study (9), differences in self-reported alcohol and drug use patterns and associated problems were found for college males as a function of family history of alcoholism. The greatest levels of alcohol and drug use were found for students with highdensity alcoholic families (first- and second-degree affected relatives), an intermediate level for students with low-density alcoholic families [first-degree affected relative(s) only], and the least in students with no affected relatives. Generally, students from high-density alcoholic families reported: greater use of alcohol, marijuana, sedatives, and cocaine; a younger age at first alcohol intoxication and at first use of marijuana; and more experience with less commonly used drug classes such as opiates and hallucinogens. Further, a greater percentage of these students reported personal alcohol- or drug-related problems as well a~ family mental health care. A similar study (14) generally supported these findings on the importance of family alcoholism density as a de-
Psychophysiological measures
terminant of vulnerability to alcohol and drug use of college males, although another study (l) utilizing a smaller sample found no significant differences. Using laboratory methodology, Finn and Pihl (4) demonstrated differences in resting heart rate and change in heart rate to a shock stressor as a function of family density of alcoholism. Specifically, resting heart rate increased following alcohol administration only in high-density subjects, with no difference between low-density and FHN subjects. In contrast, high-density subjects evidenced decreased heart rate to a shock stressor following alcohol administration, whereas low-density and FHN subjects both showed increased heart rate in this condition. Thus, both epidemiological and laboratory studies have shown family density of alcoholism to be an important determinant of response to alcohol. The present report is a follow-up to our questionnaire study described above (9) that demonstrated differences in reported alcohol and drug use patterns as a function of familial density of alcoholism. We examine here the role of familial density of alcoholism on psychophysiological responses to alcohol administration in a laboratory setting in college-aged males.
~Requests for reprints should be addressed to Mary E. McCaul, Ph.D., Alcoholism Treatment Services-D5C, The Francis Scotl Key Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224.
219
220
McCAUL, TURKKAN, SVIKIS AND BIGELOW
METHOD
Thirty-two white, college-enrolled males completed the study. Applicants were screened for personal and familial alcohol/drug use and related problems as well as other medical and psychiatric diagnoses through a mailed questionnaire and an in-person interview. The in-depth interview completed by a clinical psychologist included a brief medical screen, the Family History-Research Diagnostic Criteria (FH-RDC) (2), the Michigan Alcoholism Screening Test (MAST) (15), and the SCL-90R (3). Personal alcohol and drug use data were also obtained during the interview and included typical monthly drinking patterns, lifetime maximum drinking during a one-week period, and actual drinking levels during the week prior to the interview. A subject was classified as family history positive (FHP) if his biological father met Family History-Research Diagnostic Criteria for alcoholism (2). FHP subjects were then subdivided into affected biological father only [low-density (LD-FHP): N = 91 and both father and at least one second-degree affected relative [highdensity (HD-FHP); N = 7 ] . For each FHP subject who completed the study, a FHN match was recruited based on age, height/weight, years of school, typical and maximal alcohol consumption, and marijuana and cocaine use. A subject was classified as family history negative (FHN) if no first-degree relative met FH-RDC criteria for alcoholism. There were no significant among-group differences on any of the matching variables (all p>0.10). In four separate sessions, subjects received two secobarbital doses (100 mg and 200 mg), ethanol (1.0 g/kg) and placebo in semi-random order, using a double-blind, double-dummy procedure. Subjects drank a 16 oz beverage consisting of orange juice mixed with the appropriate dose of ethanol and consumed the fluid using a 15-min pacing procedure. Further details are provided in McCaul et al. (10,11). Experimental sessions were conducted on an outpatient basis with at least one nonstudy day separating sessions. Physiological (blood alcohol level, heart rate, skin conductance, skin temperature), psychomotor (hand-eye coordination task, static ataxia. hand tremor, digit-symbol substitution test, numeric recall) and subjective measures [4 analog items, Subjective High Assessment Scale (SHAS; 12), the Addiction Research Center Inventory (ARCI; 6)] were obtained at baseline and at four periods following drug or ethanol ingestion. Procedural details and the secobarbital vs. ethanol results have been published elsewhere (10). The present report focuses upon the family history density variable and presents only the ethanol and placebo data. This ethanol dose produced a peak blood alcohol level averaging 0.094 g% over the postingestion period. Analyses of covariance with baseline as the covariate were conducted, with one between-group factor (high-density, lowdensity and family history negative status), and two within-group factors of dose (placebo versus alcohol) and within-session timecourse. Post hoc comparisons (Tukey) were conducted of the family history groups. The results of only those variables for which significant family history differences were obtained are presented here following alcohol and placebo administration as a function of family density of alcoholism. RESULTS
There were no differences among groups on any measure at baseline. HD-FHP subjects demonstrated a heightened sensitivity to alcohol in comparison to LD-FHP and FHN subjects for subjective, physiological and psychomotor responses following ethanol ingestion; in contrast, there were no differences obtained between LD-FHP and FHN subjects on any measure. There were significant differences among the family history groups in their
Density FHP High Densi~ FHP Low
Placebo
Ethanol
100 80 "1-i-
60
o
o,
40
Z .< 20 015
I--
,,:5,
55
95
135
15
55
95
135
1500 1300
~-J
1100 900
:>O rn
~"
o
700 500
i 35
i 75
w 115
i 155
i
i
i
i
35
75
115
155
130 120
Z
110 100
oo Z
.~
cO
90 8o i 20
i
i
i
i
i
i
i
60
100
140
20
60
100
140
TIME
POST-INGESTION(rnin)
FIG. 1. Analog high, body sway displacement and skin conductance as a function of time following ethanol and placebo ingestion. Three family history groups are shown as a parameter. For analog high and body sway, each data point is an average of between 7-16 subjects (see text). For skin conductance, each data point is averaged over four 5-minute periods, and over 7-16 subjects. Values shown are adjusted means from the analyses of covariance.
analog high scores following ethanol ingestion, F(2,28)=6.62, p
Familial Density of Alcoholism: Effects on Psychophysiological Responses to Ethanol M . E. M c C A U L , I j. S. T U R K K A N , D. S. S V I K I S A N D G. E. B I G E L O W
Behavioral Pharmacology Research Unit The Johns Hopkins Universit3, School o f Medicine Baltimore, M D 21224 R e c e i v e d 2 O c t o b e r 1990; A c c e p t e d 4 J a n u a r y 1991 McCAUL, M. E., J. S. TURKKAN, D. S. SVIKIS AND G. E. BIGELOW. Familial density of alcoholism: Effects on psychophysiological responses to ethanol. ALCOHOL 8(3) 219-222, 1991.--Recent research findings suggest that the patterning of familial alcoholism may critically determine ethanol sensitivity and severity of alcohol-related problems in the offspring. The present study examined the effects of familial alcoholism density on psychophysiological responses to ethanol administration in college males. Subjects with a positive family history of alcoholism were classified into affected biological father only (LD-FHP) versus both father and at least one second-degree affected relative (HD-FHP), and were compared to family history negative (FHN) subjects. Subjects received I g/kg ethanol or placebo in a double-blind procedure. A battery of subjective, physiological and psychomotor measures was collected once prior to and four times following drink administration. HD-FHP subjects showed significantly greater subjective effects, body sway and skin conductance after alcohol ingestion than either FHN or LD-FHP subjects; in contrast, there was no difference on any measure for LD-FHP versus FHN subjects. Our findings of increased ethanol sensitivity as. a function of familial density of alcoholism strongly suggest the importance of carefully defining family history characteristics in all studies examining potential markers or risk factors for alcoholism. Alcoholism
Familial density of alcoholism
Alcohol ingestion
RECENT findings from both epidemiological and laboratory research suggest that the patterning of familial alcoholism may be a critical determinant of sensitivity to ethanol effects and the severity of alcohol-related problems in the offspring (7, 17, 19, 20). In a recent study (9), differences in self-reported alcohol and drug use patterns and associated problems were found for college males as a function of family history of alcoholism. The greatest levels of alcohol and drug use were found for students with highdensity alcoholic families (first- and second-degree affected relatives), an intermediate level for students with low-density alcoholic families [first-degree affected relative(s) only], and the least in students with no affected relatives. Generally, students from high-density alcoholic families reported: greater use of alcohol, marijuana, sedatives, and cocaine; a younger age at first alcohol intoxication and at first use of marijuana; and more experience with less commonly used drug classes such as opiates and hallucinogens. Further, a greater percentage of these students reported personal alcohol- or drug-related problems as well a~ family mental health care. A similar study (14) generally supported these findings on the importance of family alcoholism density as a de-
Psychophysiological measures
terminant of vulnerability to alcohol and drug use of college males, although another study (l) utilizing a smaller sample found no significant differences. Using laboratory methodology, Finn and Pihl (4) demonstrated differences in resting heart rate and change in heart rate to a shock stressor as a function of family density of alcoholism. Specifically, resting heart rate increased following alcohol administration only in high-density subjects, with no difference between low-density and FHN subjects. In contrast, high-density subjects evidenced decreased heart rate to a shock stressor following alcohol administration, whereas low-density and FHN subjects both showed increased heart rate in this condition. Thus, both epidemiological and laboratory studies have shown family density of alcoholism to be an important determinant of response to alcohol. The present report is a follow-up to our questionnaire study described above (9) that demonstrated differences in reported alcohol and drug use patterns as a function of familial density of alcoholism. We examine here the role of familial density of alcoholism on psychophysiological responses to alcohol administration in a laboratory setting in college-aged males.
~Requests for reprints should be addressed to Mary E. McCaul, Ph.D., Alcoholism Treatment Services-D5C, The Francis Scotl Key Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224.
219
220
McCAUL, TURKKAN, SVIKIS AND BIGELOW
METHOD
Thirty-two white, college-enrolled males completed the study. Applicants were screened for personal and familial alcohol/drug use and related problems as well as other medical and psychiatric diagnoses through a mailed questionnaire and an in-person interview. The in-depth interview completed by a clinical psychologist included a brief medical screen, the Family History-Research Diagnostic Criteria (FH-RDC) (2), the Michigan Alcoholism Screening Test (MAST) (15), and the SCL-90R (3). Personal alcohol and drug use data were also obtained during the interview and included typical monthly drinking patterns, lifetime maximum drinking during a one-week period, and actual drinking levels during the week prior to the interview. A subject was classified as family history positive (FHP) if his biological father met Family History-Research Diagnostic Criteria for alcoholism (2). FHP subjects were then subdivided into affected biological father only [low-density (LD-FHP): N = 91 and both father and at least one second-degree affected relative [highdensity (HD-FHP); N = 7 ] . For each FHP subject who completed the study, a FHN match was recruited based on age, height/weight, years of school, typical and maximal alcohol consumption, and marijuana and cocaine use. A subject was classified as family history negative (FHN) if no first-degree relative met FH-RDC criteria for alcoholism. There were no significant among-group differences on any of the matching variables (all p>0.10). In four separate sessions, subjects received two secobarbital doses (100 mg and 200 mg), ethanol (1.0 g/kg) and placebo in semi-random order, using a double-blind, double-dummy procedure. Subjects drank a 16 oz beverage consisting of orange juice mixed with the appropriate dose of ethanol and consumed the fluid using a 15-min pacing procedure. Further details are provided in McCaul et al. (10,11). Experimental sessions were conducted on an outpatient basis with at least one nonstudy day separating sessions. Physiological (blood alcohol level, heart rate, skin conductance, skin temperature), psychomotor (hand-eye coordination task, static ataxia. hand tremor, digit-symbol substitution test, numeric recall) and subjective measures [4 analog items, Subjective High Assessment Scale (SHAS; 12), the Addiction Research Center Inventory (ARCI; 6)] were obtained at baseline and at four periods following drug or ethanol ingestion. Procedural details and the secobarbital vs. ethanol results have been published elsewhere (10). The present report focuses upon the family history density variable and presents only the ethanol and placebo data. This ethanol dose produced a peak blood alcohol level averaging 0.094 g% over the postingestion period. Analyses of covariance with baseline as the covariate were conducted, with one between-group factor (high-density, lowdensity and family history negative status), and two within-group factors of dose (placebo versus alcohol) and within-session timecourse. Post hoc comparisons (Tukey) were conducted of the family history groups. The results of only those variables for which significant family history differences were obtained are presented here following alcohol and placebo administration as a function of family density of alcoholism. RESULTS
There were no differences among groups on any measure at baseline. HD-FHP subjects demonstrated a heightened sensitivity to alcohol in comparison to LD-FHP and FHN subjects for subjective, physiological and psychomotor responses following ethanol ingestion; in contrast, there were no differences obtained between LD-FHP and FHN subjects on any measure. There were significant differences among the family history groups in their
Density FHP High Densi~ FHP Low
Placebo
Ethanol
100 80 "1-i-
60
o
o,
40
Z .< 20 015
I--
,,:5,
55
95
135
15
55
95
135
1500 1300
~-J
1100 900
:>O rn
~"
o
700 500
i 35
i 75
w 115
i 155
i
i
i
i
35
75
115
155
130 120
Z
110 100
oo Z
.~
cO
90 8o i 20
i
i
i
i
i
i
i
60
100
140
20
60
100
140
TIME
POST-INGESTION(rnin)
FIG. 1. Analog high, body sway displacement and skin conductance as a function of time following ethanol and placebo ingestion. Three family history groups are shown as a parameter. For analog high and body sway, each data point is an average of between 7-16 subjects (see text). For skin conductance, each data point is averaged over four 5-minute periods, and over 7-16 subjects. Values shown are adjusted means from the analyses of covariance.
analog high scores following ethanol ingestion, F(2,28)=6.62, p
