Department of Psychiatry (116A), University of California, San Diego and the VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161-2002, USA
* Author to whom correspondence should be addressed at: Department of Psychiatry (116A), University of California, San Diego and the VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161-2002. Tel.: (858) 552-8585 (ext.) 7978; Fax: (858) 552-7424; Email: mschuckit{at}ucsd.edu
(Received 18 March 2004; first review notified 24 April 2004; in revised form 24 May 2004; accepted 24 May 2004)
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ABSTRACT |
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INTRODUCTION |
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The need for higher amounts of alcohol for a desired effect from early in the drinking career is hypothesized to alter a person's cognitive expectations of how alcohol might affect them, impact on social decisions such as the choice of heavier-drinking friends, and relate to the probability of exhibiting behaviors that include the use of alcohol to cope with stress (Schuckit and Smith, 1996; Schuckit, 1998
; Dodge et al., 2003
; Schuckit et al., submitted for publication). Here, a social information processing bias might be created by experiences with alcohol that could contribute to developing a social milieu in which drinking more per occasion is encouraged, with subsequent physiological tolerance developing in the context of the heavier drinking, and changes in the cognitive set through which an individual determines whether their own drinking pattern is moderate or excessive. While a low LR earlier in life predicts future alcohol problems, it is not known whether this need for more drinks for effects might also contribute to the continuation of heavier drinking with advancing age.
Most studies have measured LR through alcohol challenges that document changes in subjective feelings of intoxication, motor performance, and alterations in several physiological measures, but these evaluations are expensive and time consuming (Schuckit et al., 1997a; Schuckit and Smith, 2000
). An alternative measure of LR uses a 12-item self-report questionnaire, asking subjects to indicate the number of drinks required for any of up to four effects during the approximate first five times of drinking alcohol and during more recent epochs such as the past 3 months (Schuckit et al., 1997a
,b, 2001b; Daeppen et al., 2000
). Evaluations of LR using this Self-Report of the Effects of Alcohol (SRE) instrument found that early life SRE correlated (r = 0.60) with LR from alcohol challenges, and had a retest reliability over several years reaching 0.8 (Schuckit et al., 1997a
,b
, 2003
; Daeppen et al., 2000
). SRE scores have been shown to relate in the predicted directions to a family history (FH) of alcoholism, a person's alcohol-related problems, as well as AUDs in adolescent populations, groups in the military, and general population samples in the US and Europe. The higher scores on this measure indicate more drinks required to have an effect, implying a likely lower level of response (or lower sensitivity) for an individual during an alcohol challenge.
No data have been published regarding changes in LR in the same person over long periods of time. There are several reasons to predict that a person's SRE score might decrease as they age (i.e. they will report fewer drinks for an effect, or have an overall higher LR). First, LR is compared across groups at specific blood alcohol concentrations (BACs), and the BAC reached per drink is likely to increase with advancing age (Kalant, 1998; Wang et al., 2001
; Lynskey et al., 2003
). This may occur as a consequence of increases in the percent body fat (leading to higher BACs achieved per standard drink because of less body water, as fat contains less water than muscle), and potential decreases with advancing age in the efficiency of the liver in oxidizing substances such as alcohol. The increase in LR (or lower SRE score) with age may also relate to enhanced intensities of reaction of the brain to depressant drugs such as alcohol as a person grows older (Kalant, 1998
; Wang et al., 2001
). Additional data support the probability that individuals are likely to consume less alcohol with advancing years (Lynskey et al., 2003
), a phenomenon that might relate to the greater effect of alcohol per drink.
The optimal way to measure changes in the LR to alcohol over time in the same individual would be to carry out alcohol challenges at different ages. The absence of data in this area may reflect the high costs in following individuals over appropriate periods of time (perhaps a decade or more), as well as the resources necessary to bring subjects back to the laboratory when they no longer live in the same city in which the initial evaluation occurred. A third problem rests with the proportion of subjects who may no longer be appropriate for direct alcohol challenges as a result of new medical conditions, the associated use of medications, and contraindications that might be related to the development of an AUD.
The self-report SRE offers a relatively inexpensive opportunity to describe a person's perception of his or her LR to alcohol at different ages. The analyses below present such results.
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METHODS |
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Probands had been originally preliminarily identified at approximately age 20 through questionnaires mailed to students and nonacademic staff at the University of California San Diego. Those selected included individuals who indicated a father with sufficient problems to meet the criteria for alcohol dependence in the third revised Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-III-R) (American Psychiatric Association, 1987), as well as matched family history negative (FHN) controls. All participants had experience with alcohol, and none met criteria for alcohol dependence at the time of testing. Final selection was made after a face-to-face structured interview to corroborate background data. Subjects subsequently received an alcohol challenge that included a session using 0.75 ml/kg of ethanol which was consumed over a 10 min period, and the LR evaluated over the subsequent 3 h (Schuckit and Smith, 1996
, 2000
).
All probands, both family history positive and negative, were located 10 years after initial testing (T10), when 99.3% participated in the follow-up evaluation. Here, a face-to-face interview similar to the Structured Clinical Interview for DSM-III-R (SCID) (Spitzer et al., 1992
) was used to gather data from both the subject, and separately, from an additional informant, usually the spouse (Schuckit and Smith, 1996
, 2000
). These interviews evaluated alcohol and drug disorders, as well as major psychiatric conditions. The subsequent follow-up at 15 years (T15) used a similar protocol, but incorporated the retrospective self-report measure of LR, the SRE, which had only recently been developed and tested. The relevant elements of the follow-up evaluations, including face-to-face interviews and SRE's, were repeated for the ongoing 20 year (T20) protocol.
The SRE is a 12-item self-report measure that asks subjects to indicate the number of standard drinks (12 g of ethanol) required for each of up to four effects ranging from feeling intoxicated through falling asleep when they did not wish to (Schuckit et al., 1997a,b
, 2003
; Daeppen et al., 2000
). Individuals are instructed to indicate only the numbers of standard drinks for experiences they actually had (leaving others blank) at each time point, including the approximately first five times of drinking, and the most recent 30 days or last time they had a drink. For these analyses, and for most reports in the literature, the evaluations focus on the first five and recent 30-day periods. The score for the specific time frame on the SRE is determined by summing the number of drinks required for each endorsed effect during a time frame (e.g. first five times of drinking), and dividing that by the number of effects endorsed. Thus, the larger the number of drinks required for an effect on the SRE, the lower the intensity of response to alcohol is likely to be in an alcohol challenge protocol (i.e. the self-report number of drinks correlates negatively with the LR determined on alcohol challenges).
In the current analyses, the estimated number of drinks required for the first five times of drinking was determined retrospectively at the initial administration of the SRE during T15. First five time scores were also estimated again at T20, with the two values correlating at 0.66. As the T15 rating was more proximal to the early drinking, that value was used in the analyses. At both T15 and T20, SRE scores were also determined for the number of drinks required for various effects during a recent interval (e.g. the past 3 months) prior to the 15- and 20-year follow-ups.
Data were analyzed by evaluating the pattern of SRE scores across three time points, including first five, recent experiences at T15, and recent data regarding T20. The overall change over time was determined through ANOVA for the 202 men and for relevant subgroups. Partial eta effect sizes () are included for relevant analyses (small
0.05, medium
0.06, and large
0.15). The SRE scores over time were also compared for lighter and heavier drinkers (i.e. men whose recent maximum drinks at both T15 and T20 fell below the median versus remaining subjects), using a mixed model ANOVA, with time as the repeated measure.
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RESULTS |
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As shown in Table 1, recent period SRE scores at T15 and T20 covaried with contiguous maximum drinking quantity, illicit drug use, smoking status, and use of depressant medications, but not with weight measured at the same time. In order to select the most appropriate covariates for the analyses that follow, the significant items at T15 were placed into a multiple regression analysis predicting T15 recent SRE scores, with only maximum alcohol quantities adding significantly to the equation. The procedure was then repeated for T20, and when all significant variables were considered, recent use of depressants and maximum drinks entered the equation. When T15 and T20 maximum drinks and T20 use of depressants were evaluated together, only the T15 drink and T20 drug contributed to the regression.
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Figure 2 takes these analyses further as the dotted line describes the SRE results for 70 light drinkers, defined as those whose maximum drinking at both T15 and T20 fell below the median. For this population, the maximum drinks in the 6 months prior to T15 was 2.9 ± 1.38, and at T20 was 2.9 ± 1.00. These analyses corroborate the significant decrease in the number of drinks required for an effect with age (F[2, 138] = 11.55, P < 0.001), with an even higher effect size (). The 70 men reported mean quantities of 1.4 ± 0.71 and 1.3 ± 0.51 drinks per occasion at T15 and T20, with frequencies at the two time points of 6.6 ± 7.80 and 7.3 ± 7.65 drinking days per month.
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All of the analyses reported for the data in Figs 1 and 2 were repeated for the 120 FHP and 82 FHN subjects. Regarding Fig. 1, both FH groups demonstrated a decrease in SRE over time, but only when covariates were used (FHN: F[2, 160] = 10.54, P < 0.001 and FHP: F[2, 234] = 7.67, P = 0.001). The changes in SRE over time were significant for both FH groups among nonalcoholics, even without the use of covariates (FHN: F[2, 120] = 6.21, P < 0.01 and FHP: F[2, 116] = 5.42, P < 0.01). Regarding Fig. 2, for FHNs the lighter drinkers continued to show a decrease in SRE over time, even without the use of covariates (F[2, 62] = 5.94, P < 0.01), but no significant change over time was observed for FHP light drinkers (F[2, 68] = 0.02, P = 0.98). Both FHP and FHN heavier drinkers, however, did demonstrate the significant change over time noted in Fig. 2 (FHN: F[2, 94] = 306, P = 0.051 and FHP: F[2, 160] = 4.23, P < 0.02). Finally, regarding the analyses of FH groups separately, when the mixed design ANOVA was repeated for each family group separately, the group by time effect remained significant for both FHNs (F[2, 160] = 3.97, P < 0.03) and for FHPs (F[2, 236] = 4.98, P < 0.01), even without the use of covariates.
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DISCUSSION |
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When the entire group was evaluated, a significant decrease in the SRE scores over time was only observed after covarying for the recent intake of depressants, especially alcohol, benzodiazepines and muscle relaxants. These initial results indicated the possibility that there might be at least two opposing processes regarding the response to alcohol with age. Supporting this contention were results observed when the SRE scores were evaluated in nonalcoholics and, separately, in lighter drinkers. The diminution in the number of drinks required for effects was clearly observed in nonalcoholics and in lighter drinkers, even without the use of covariates. However, among the heavier drinkers, an apparent increase in the number of drinks required for effects was observed over time, at least when covariates were considered. Even though the recent drinking pattern was among the covariates used in the analyses, it is also possible that changes in the alcohol consumption in the US over the last several decades (Greenfield and Room, 1997) may have contributed to drinking practices in these subjects, with subsequent lighter drinking and a loss of tolerance.
The findings for the subjects overall were generally corroborated when FHP and FHN subgroups were considered separately. The only exception occurred for data relevant to the lighter drinkers where the pattern in Fig. 2 was demonstrated for FHNs, but was not observed for FHPs. The absence of change over time for light-drinking FHPs might reflect the relatively high overall prevalence of a low LR to alcohol in FHPs (i.e. a higher SRE first five score) earlier in life, even among individuals who may have deliberately limited their alcohol intake. This might result in a maintenance of the innate high SRE values with advancing age, creating a general absence of change in SRE over time despite light drinking. This hypothesis will need to be reevaluated in another population before any solid conclusions can be drawn.
There are several implications for the results reported in this paper. First, the finding of a more intense reaction to a dose of depressants such as alcohol with advancing age (i.e. fewer drinks required for an effect) reported in the literature (Kalant, 1998; Wang et al., 2001
) may primarily be true among lighter drinkers. For those who experience it, this increasing reaction might be one of several factors that contribute to the tendency for most individuals to decrease the amount of alcohol they drink per occasion as they grow older.
A second implication is that, in heavier drinkers and those with low LR's, the intensity of response to alcohol may tend to be a more stable trait, and might even increase a bit over time. Prior research has demonstrated that requiring more drinks for an effect (i.e. being less reactive or sensitive to alcohol) is observed in several groups at high potential risk for alcohol use disorders, and tends to predict future alcohol-related life problems (Ehlers et al., 1999; Wall et al., 1999
; Schuckit and Smith, 2000
). The current data indicate that individuals who reported that they required higher doses of alcohol for an effect early in their drinking careers may tend to maintain that characteristic over time. These results are consistent with the possibility that the need for more drinks for an effect might not only contribute to the onset of heavier drinking and alcohol-related life problems, but might also help perpetuate these conditions.
A third implication of the current findings relates to the optimal structure of studies attempting to understand more about changes in the response to alcohol with aging. Such epidemiological and laboratory-oriented evaluations will need to carefully control for the current intake pattern of all depressant drugs, including alcohol, and might benefit from understanding more about a person's intensity of response to alcohol earlier in life.
To place the current data in perspective, the ideal study of changes in response to alcohol with age requires repetitive alcohol challenges over several decades. The analyses reported here used a much less expensive approach that incorporated SRE-based self-reports. While the two retrospective reports of the number of drinks required for effects early in life gathered at T15 and T20 correlated at almost 0.7, the absence of prospective data regarding this phenomenon is an important caveat. On the other hand, at least among heavier drinkers, the retrospective first five times SRE scores appeared to be similar to those for recent reactions at both 15- and 20-year follow-ups. It is also important to note that the population evaluated here was limited to relatively well-educated Caucasian males. While this is a major subgroup in the US, it was not possible to determine the generalization of results to women and minorities. However, a recent paper demonstrated that, at least among children of alcoholics, there were no major differences in intensity of response to alcohol noted across the genders nor for Anglo versus Latino populations (Schuckit et al., in press).
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ACKNOWLEDGEMENTS |
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REFERENCES |
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Baldwin, H. A., Wall, T. L., Schuckit, M. A. and Koob, G. F. (1991) Differential effects of ethanol on punished responding in the P and NP rats. Alcoholism: Clinical and Experimental Research 15, 700704.[ISI][Medline]
Daeppen, J.-B., Landry, U., Pécoud, A., Decrey, H. and Yersin, B. (2000) A measure of the intensity of response to alcohol to screen for alcohol use disorders in primary care. Alcohol and Alcoholism 35, 625527.
Dodge, K. A., Lansford, J. E., Salzer Burks, V., Bates, J. E., Pettit, G. S., Fontaine, R. and Price, J. M. (2003) Peer rejection and social information-processing factors in the development of aggressive behavior problems in children. Child Development 74, 374393.[CrossRef][ISI][Medline]
Ehlers, C. L., Garcia-Andrade, C., Wall, T. L., Cloutier, D. and Phillips, E. (1999) Electroencephalographic responses to alcohol challenge in Native American Mission Indians. Biological Psychiatry 45, 776787.[CrossRef][ISI][Medline]
Erblich, J. and Earleywine, M. (1999) Children of alcoholics exhibit attenuated cognitive impairment during an ethanol challenge. Alcoholism: Clinical and Experimental Research 23, 476482.[ISI][Medline]
Greenfield, T. K. and Room, R. (1997) Situational norms for drinking and drunkenness: trends in the U.S. adult population, 19791990. Addiction 92, 3347.[ISI][Medline]
Heath, A. C., Madden, P. A., Bucholz, K. K. et al. (1999) Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk. Psychological Medicine 29, 10691081.[CrossRef][ISI][Medline]
Kalant, H. (1998) Pharmacological interactions of ageing and alcohol. In Alcohol Problems and Ageing. Research monograph no. 33.: Gomberg, E. S. L., Hegedus, A. M., Zucker, R. A. eds, pp. 99116. US Department of Health and Human Services, Bethesda.
Lynskey, M. T., Day, C. and Hall, W. (2003) Alcohol and other drug use disorders among older-aged people. Drug and Alcohol Review 22, 125133.[ISI][Medline]
McGue, M. (1999) The behavioral genetics of alcoholism. Current Directions Psychological Science 8, 109115.[CrossRef][ISI]
Pollock, V. E. (1992) Meta-analysis of subjective sensitivity to alcohol in sons of alcoholics. American Journal of Psychiatry 149, 15341538.[Abstract]
Prescott, C. A. and Kendler, K. S. (1999) Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. American Journal of Psychiatry 156, 3440.
Schuckit, M. A. (1998) Biological, psychological and environmental predictors of the alcoholism risk: A longitudinal study. Journal of Studies on Alcohol 59, 485494.[ISI][Medline]
Schuckit, M. A. (2002) Vulnerability factors for alcoholism. In Neuropsychopharmacology: The Fifth Generation of Progress, Davis, K. ed., Chapter 98, pp. 13991411. Lippincott Williams & Wilkins Co., Baltimore, MD.
Schuckit, M. A. and Smith, T. L. (1996) An 8-year follow-up of 450 sons of alcoholics and control subjects. Archives of General Psychiatry 53, 202210.[Abstract]
Schuckit, M. A. and Smith, T. L. (2000) The relationships of a family history of alcohol dependence, a low level of response to alcohol and six domains of life functioning to the development of alcohol use disorders. Journal of Studies on Alcohol 61, 827835.[ISI][Medline]
Schuckit, M. A., Edenberg, H. J., Kalmijn, J. et al. (2001a) A genome-wide search for genes that relate to a low level of response to alcohol. Alcoholism: Clinical and Experimental Research 25, 323329.[ISI][Medline]
Schuckit, M. A., Kraft, H. S., Hurtado, S. L., Tschinkel, S. A., Minagawa, R. and Shaffer, R. A. (2001b) A measure of the intensity of response to alcohol in a military population. American Journal of Drug and Alcohol Abuse 27, 749757.[CrossRef][ISI][Medline]
Schuckit, M. A., Mazzanti, C., Smith, T. L., Ahmed, U., Radel, M., Iwata, M. and Goldman, D. (1999) Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study. Biological Psychiatry 45, 647651.[CrossRef][ISI][Medline]
Schuckit, M. A., Smith, T. L., Danko, G. P. and Isacescu, V. (2003) The level of response to alcohol measured on the Self-Rating of the Effects of Alcohol (SRE) questionnaire in a group of 40-year-old women. American Journal of Drug and Alcohol Abuse 29, 191201.[CrossRef][ISI][Medline]
Schuckit, M. A., Smith, T. L. and Kalmijn, J. (2004) Findings across subgroups regarding the level of response to alcohol as a risk factor for alcohol use disorders (AUDs): Women and Latinos. Alcoholism: Clinical and Experimental Research, in press.
Schuckit, M. A., Smith, T. L. and Tipp, J. E. (1997a) The Self-Rating of the Effects of Alcohol (SRE) form as a retrospective measure of the risk for alcoholism. Addiction 92, 979988.[CrossRef][ISI][Medline]
Schuckit, M. A., Tipp, J. E., Smith, T. L., Wiesbeck, G. A. and Kalmijn, J. (1997b) The relationship between self-rating of the effects of alcohol and alcohol challenge results in ninety-eight young men. Journal of Studies on Alcohol 58, 397404.[ISI][Medline]
Spitzer, R., Williams, J., Gibbon, M. and First, M. B. (1992) The structured clinical interview for DSM-III-R (SCID) 1: history, rationale, and description. Archives of General Psychiatry 49, 624629.[Abstract]
Volavka, J., Czobor, P., Goodwin, D. W. et al. (1996) The electroencephalogram after alcohol administration in high-risk men and the development of alcohol use disorders 10 years later: Preliminary findings. Archives of General Psychiatry 53, 258263.[Abstract]
Wall, T. L., Johnson, M. L., Horn, S. M., Carr, L. G., Smith, T. L. and Schuckit, M. A. (1999) Evaluation of the Self-Rating of the Effects of Alcohol form in Asian American with aldehyde dehydrogenase polymorphisms. Journal of Studies on Alcohol 60, 784789.[ISI][Medline]
Wang, P. S., Bohn, R. L., Glynn, R. J., Mogun, H. and Avorn, J. (2001) Hazardous benzodiazepine regimens in the elderly: Effects of half-life, dosage, and duration on risk of hip fracture. American Journal of Psychiatry 158, 892898.[ISI][Medline]
Wilhelmsen, K. C., Schuckit, M., Smith, T. L., Lee, J. V., Segall, S. K., Feiler, H. S. and Kalmijn, J. (2003) Genomic scan for loci that lead to low level response to alcohol as established by an alcohol challenge. Alcoholism: Clinical and Experimental Research 27, 10411047.[ISI][Medline]
Zucker, R. A., Ellis, D., Bingham, C. R. and Fitzgerald, H. (2000) The development of alcoholic subtypes risk variation among alcoholic families during the early childhood years. In Children of Alcoholics: Selected Readings, Vol. II, Abbott, S. ed., National Association of Children of Alcoholics, Rockville, MD.
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