Genetic origins of the association between verbal ability and alcohol dependence symptoms in young adulthood.

BACKGROUND: Cognitive deficits in alcohol dependence (AD) have been observed, poorer verbal ability being among the most consistent findings. Genetic factors influence both cognitive ability and AD, but whether these influences overlap is not known. METHOD: A subset of 602 monozygotic (MZ) and dizygotic (DZ) twins from FinnTwin16, a population-based study of Finnish twins, was used to study the associations of verbal ability with DSM-III-R diagnosis and symptoms of AD, the maximum number of drinks consumed in a 24-h period, and the Rutgers Alcohol Problem Index (RAPI) scores. These twins, most of them selected for within-pair discordance or concordance for their RAPI scores at age 18.5 years, were studied with neuropsychological tests and interviewed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) in young adulthood (mean age 26.2 years, range 23-30 years). RESULTS: All alcohol problem measures were associated with lower scores on the Vocabulary subtest of the Wechsler Adult Intelligence Scale - Revised (WAIS-R), a measure of verbal ability. In bivariate genetic models, Vocabulary and the alcohol problem measures had moderate heritabilities (0.54-0.72), and their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). CONCLUSIONS: Poorer verbal ability and AD have partly overlapping biological etiology. The genetic and environmental influences on the development of cognitive abilities, alcohol problems and risk factors for AD should be studied further with prospective longitudinal designs.

Genetic influences on blood pressure with the cold-pressor test: a twin study.

OBJECTIVES: To determine the genetic and environmental contributions to resting blood pressure, the level of blood pressure during the cold-pressor test and the increase in blood pressure with the cold-pressor test in an adult cohort of normotensive twins. DESIGN AND METHODS: Ninety-one monozygotic and 41 dizygotic normal twin pairs were recruited by advertisement. The mean age was 34 +/- 14 years (mean +/- SD). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were measured continuously at the finger (using a Finapres device) and verified at the upper arm oscillometrically (using a Dinamap device) every minute. The cold-pressor test was conducted by immersing the non-dominant hand into cold (< 4 degrees C) water for 2 min. Statistical analysis was performed by using the SPSS program; parameters of the quantitative genetic models were estimated by path-analysis techniques using the LISREL 8 program. RESULTS: Heritability estimates of additive genetic effects were statistically significant for SBP and DBP but not for heart rate during rest and during the cold-pressor test. Furthermore, the path analysis indicated shared as well as specific genetic components both for the blood pressure level at rest and for that during the cold-pressor test. However, the genetic influences on the blood pressure level at rest and on the increase in blood pressure during the cold-pressor test (the blood pressure level during the cold-pressor test minus that during rest) were entirely independent of one another. CONCLUSIONS: A significant genetic covariation exists for SBP and DBP during rest and during the cold-pressor test, as well as a significant genetic variation that is specific to the cold-pressor stress condition. These findings suggest that different genes or sets of genes contribute to blood pressure regulation during rest and to blood pressure reactivity to cold-pressor stress.

Exploring gene-environment interactions: socioregional moderation of alcohol use.

Examples of gene-environment interaction in human behavioral data are relatively rare; those that exist have used simple, dichotomous measures of the environment. The authors describe a model that allows for the specification of more continuous, more realistic variations in environments as moderators of genetic and environmental influences on behavior. Using data from a population-based Finnish twin study, the authors document strong moderating effects of socioregional environments on genetic and environmental influences on adolescent alcohol use, with nearly a five-fold difference in the magnitude of genetic effects between environmental extremes. The incorporation of specific environmental measures into genetically informative designs should prove to be a powerful method for better understanding the nature of gene-environment interaction and its contribution to the etiology of behavioral variation.

Experimental dissociation of behavioral and cardiovascular outcome in the borderline hypertensive rat.

F1 Offspring of hypertensive and normotensive rats (BHR) were reared with either hypertensive (SHR) or normotensive (WKY) cagemates, and observations were conducted at two developmental periods to assess the effects of rearing condition on the social environment and the behavior of BHR subjects. SHR displayed significantly more agonistic behavior during development than WKY, and BHR subjects reared with SHR were the targets of significantly more agonistic behavior than BHR subjects reared with WKY cagemates. BHR reared with SHR initiated twice as much agonistic behavior as BHR reared with WKY. When heart rate and blood pressure were assessed at 75-80 days of age, however, neither the alterations in developmental social environment nor the alterations in the behavioral characteristics of BHR were associated with differences in cardiovascular variables. The results do not support a causal connection between behavioral characteristics and cardiovascular outcome.

Blood pressure, heart rate, and regional resistance in behavioral defense.

Rats were instrumented with arterial catheters and directional pulsed Doppler flow probes for measurement of arterial blood pressure, heart rate, and blood flow in the renal, mesenteric, and hindquarter vascular beds. When tested as intruders in a resident-intruder aggression test, subjects responded to resident attack with species-characteristic defensive behavior and the "defense reaction" pattern of increased heart rate, renal resistance, and mesenteric resistance, and decreased hindquarter resistance. Blood pressure was variable, but sustained increases in blood pressure were rarely observed. The maintenance of blood pressure during species-specific defensive behavior can be contrasted with the sustained pressor responses observed in the centrally elicited defense reaction. The combination of pulsed Doppler technology and the resident-intruder paradigm appears to be a promising method for investigating the mechanisms of cardiovascular adjustment to behavioral defense.

Effects of behavior and social condition on cardiovascular response to footshock stress.

Rats were instrumented with arterial catheters and directional-pulsed Doppler flow probes for assessment of blood pressure, heart rate, and blood flow in the renal, mesenteric, and hindquarter vascular beds. Subjects were tested in an intermittent shock procedure under paired and isolated social conditions and the cardiovascular indices associated with first shock, prone immobile behavior, upright behavior, and boxing behavior were recorded. Both shock procedures resulted in increased heart rate, mesenteric resistance, and renal resistance, as well as decreased hindquarter resistance. Blood pressure response was variable. Social and behavioral conditions generally accounted for little variance in cardiovascular indices during the treatments. Blood pressure assessed 2.5 min after the last shock was significantly higher in the isolated shock condition. In the context of divergent results from previous research in the area, the current results are most consistent with the view that a similar form of cardiovascular adjustment is present under paired and isolated shock, but that under some conditions the presence of a conspecific or the opportunity to fight may attenuate cardiovascular response to shock.

A developmental genetic analysis of adult personality: extraversion and neuroticism from 18 to 59 years of age.

Developmental genetic analyses were conducted on Extraversion (E) and Neuroticism (N) scale scores from nearly 15,000 male and female Finnish twins, ages 18-53 at baseline, who were tested on 2 occasions, 6 years apart. Significant genetic effects on both traits were found, at all ages, in men and women, on each measurement occasion. For E, heritability was invariant across sex but decreased from late adolescence to the late 20s, with a smaller additional decrease at about 50 years of age. Heritability for N also decreased from late adolescence to late 20s and remained stable thereafter. For all ages after the early 20s, heritability of N was significantly higher among women. Means for E and N were sex-dependent and, apparently, influenced by cohort and time of assessment, as well as by age. There was little evidence of new genetic contributions to individual differences after age 30; in contrast, significant new environmental effects emerged at every age.

Familial and socioregional environmental effects on abstinence from alcohol at age sixteen.

OBJECTIVE: This study identifies, in genetically informative data, familial and socioregional environmental influences on abstinence from alcohol at age 16. METHOD: Data are from FinnTwin 16, a population-based study of five consecutive birth cohorts of Finnish twins (N = 5,747 twin individuals), yielding 2,711 pairs of known zygosity. Measures of alcohol use, embedded into a health-habits questionnaire, were taken from earlier epidemiological research with nontwin Finnish adolescents. The questionnaire was administered sequentially to all twins as they reached age 16. Separate questionnaires, including measures of alcohol use and screening questions for alcohol problems, were received from 5,243 of the twins' parents. RESULTS: Abstinence from alcohol to age 16 exhibits very significant familial aggregation, largely due to nongenetic influences. Abstinence rates are influenced by socioregional variation, sibling interaction effects and parental drinking patterns. Sibling and parental influences are greater in some regional environments than in others: the relative likelihood that a twin abstains, given that the co-twin does, or that both parents do, is shown to be modulated by socioregional variation. CONCLUSION: Environmental contexts affect the likelihood of maintaining abstinence from alcohol to midadolescence, and socioregional variation modulates influences of siblings and parents. The results illustrate how genetically informative data can inform prevention research by identifying target variables for intervention efforts.

Pubertal timing and substance use: associations between and within families across late adolescence.

In the present study, between-family analyses of data from adolescent twin girls offer new evidence that early menarche is associated with earlier initiation and greater frequency of smoking and drinking. The role of personality factors and peer relationships in that association was investigated, and little support was found for their involvement. Novel within-family analyses replicating associations of substance use with pubertal timing in contrasts of twin sisters selected for extreme discordance for age at menarche are reported. Within-family replications demonstrated that the association of pubertal timing with substance use cannot be explained solely by between-family confounds. Within-family analyses demonstrated contextual modulation of the influence of pubertal timing: Its impact on drinking frequency is apparent only among girls in urban settings. Sibling comparisons illustrate a promising analytic tool for studying diverse developmental outcomes.

Using cognitive science methods to assess the role of social information processing in sexually coercive behavior.

Seventy-four undergraduate men completed cognitive performance tasks assessing perceptual organization, classification, and category learning, as well as self-report measures relevant to sexual coercion. The stimuli were slides of Caucasian women who varied along affect and physical exposure (i.e., sensuality) dimensions. Data were analyzed using a weighted multidimensional scaling model, signal-detection theory analyses, and a connectionist learning model (RASHNL; J. K. Kruschke & M. K. Johansen, 1999). Individual differences in performance on the classification and category-learning tasks were congruent with individual differences in perceptual organization. Additionally, participants who showed relatively more attention to exposure than to affect were less sensitive to women's negative responses to unwanted sexual advances. Overall, the study demonstrates the feasibility and utility of cognitive science methods for studying information processing in psychopathology.

Aggressive boys in the classroom: biased attributions or shared perceptions?

This study of 32 aggressive (AG) and 32 nonaggressive (NA) boys applied a social information processing analysis to interactions between children and their teachers. In a cue reading task, AG and NA subjects estimated teacher anger in ambiguous situations where the targets of the teacher behavior were the subjects, NA peers, and AG peers. AG boys predicted that greater teacher anger would be directed toward themselves than did NA boys. However, this could not be interpreted as an attributional bias specific to AG boys, because both NA and AG boys predicted that greater hostility would be directed toward AG boys. Target status was the primary determinant of cue interpretation. AG boys were more likely than NA boys to choose aggressive solutions to problems involving teachers and to judge aggressive solutions to be competent. The results suggested that NA subjects were actually more effective than AG subjects in enacting an aggressive response.

Common genetic influences on BMI and age at menarche.

Genetic influences on variability of body weight and onset of menarche are well known. To investigate the genetic and environmental contributions to the association of body weight with onset of menarche, we studied Finnish twins from consecutive birth cohorts (the FinnTwin16 study) ascertained from the national population registry, which identifies nearly 100% of all living twins. Baseline questionnaires were mailed to the twins within 60 days of their sixteenth birthday and later to older sibs of the twins. Pairwise response rates (approximately 85% across gender and zygosity) and 30 months of data collection yielded results from 1283 twin pairs. The questionnaires included a survey of health habits and attitudes, a symptom checklist, MMPI personality scales, and a survey of relationships with parents, peers, and the co-twin. Age at menarche was reported by 468 monozygotic (MZ) girls, 378 girls from like-sex dizygotic (FDZ) pairs, 434 girls from opposite-sex (OSDZ) pairs, and 141 older female sibs of the twins. The one-month test-retest reliability of age at menarche in an independent sample (N = 136) of 16-year-olds from a national survey was 0.96. Girls from OSDZ pairs had a significantly higher mean age at menarche (13.33 yr) than FDZ girls (13.13 yr) (difference, 0.20 yr; 95% confidence interval, 0.05-0.35). The MZ correlation for age at menarche was 0.75, the DZ correlation was 0.31, and the sib-twin correlation was 0.32. A bivariate twin analysis of age at menarche and body mass index (wt/ht2) indicated that 37% of the variance in age at menarche can be attributed to additive genetic effects, 37% to dominance effects, and 26% to unique environmental effects. The correlation between additive genetic effects on age at menarche and body mass index was 0.57, indicating a substantial proportion of genetic effects in common.

Individual differences in adolescent religiosity in Finland: familial effects are modified by sex and region of residence.

Data from 16-year-old Finnish twin pairs were used to estimate familial effects on religiosity and the modification of those effects by sex and residential region. The sample of 2265 twin boys and 2521 twin girls formed 779 monozygotic and 1614 dizygotic pairs, 785 of the same sex and 829 of opposite sex. We compared religiosity scores of twins living in more rural and traditional northern Finland with those living in the more urban and secular southern region. Girls had higher religiosity scores than did boys, and twins living in northern Finland had higher religiosity scores than those resident in southern Finland. Correlations for monozygotic twins were slightly higher than those for dizygotic twins, and covariance modeling found modest heritability of religiosity [11% (95% CI 0-24) for girls; 22% (95% CI 6-38) for boys], and substantial shared environmental effects [60% (95% CI 49-69) and 45% (95% CI 31-57)] among girls and boys, respectively. The correlation between shared environmental effects in boys and girls was estimated to be 0.84 (95% CI 0.73-0.99). In analyses distinguishing region of residence, girls living in southern Finland were found to have significantly higher unshared environmental effects than girls in northern Finland, while boys living in the urban south appeared to have lower shared environmental effects, and higher additive genetic effects, than boys living in the rural north.

Longitudinal analyses of the determinants of drinking and of drinking to intoxication in adolescent twins.

Genetic and environmental determinants of self-reported alcohol consumption were investigated in a sample of 2513 twin pairs who were first assessed at age 16 and were followed-up at age 17. At age 16, 77% of the sample was drinking, and 65% of drinkers reported drinking to intoxication. Both drinking and drinking to intoxication increased at the 1-year follow-up. Model fitting indicated that most of the variance in drinking initiation was due to shared environmental effects but that shared environmental effects were less important, and additive genetic effects were more important, in explaining frequency of drinking among subjects who had already initiated drinking. Similarly, shared environmental effects explained most of the variation in initiation of drinking to intoxication but were less important in explaining frequency of intoxication among subjects who had already initiated drinking to intoxication. The magnitude of genetic and environmental estimates for males and females did not differ significantly, but it was clear that either different genetic factors or different shared environmental factors were influencing males and females. For all drinking variables studied, shared environmental effects decreased from age 16 to age 17, while additive genetic effects increased from age 16 to age 17.

Drinking or abstaining at age 14? A genetic epidemiological study.

BACKGROUND: Regular drinking by age 14 years is a significant risk factor for alcoholism, and genetically informative data suggest that whether a young adolescent abstains or drinks is largely attributable to familial (or other shared) environmental factors. METHODS: Three consecutive birth cohorts of Finnish twins, enrolled into a longitudinal study at age 11 to 12 years, completed a follow-up questionnaire within 3 months of their 14th birthdays. The sample included 1380 twin sisters and 1330 twin brothers at age 14, and at that age, 35.4% reported using alcohol. Genetic analyses (model-fitting of twin pair data) and epidemiological analyses (logistical regressions of data from individual twins) were conducted to examine predictive factors of drinking versus abstinence at age 14. RESULTS: Polychoric correlations were substantial across all same-sex twin pairs but were lower for brother-sister twins, suggesting significant influences of common environments, with some sex-specific effects. Common environmental effects were equivalent in male and female adolescents and accounted for 76% of the total variation in abstinence/drinking. Logistical regression analyses among 2206 individual twins with complete data on risk-relevant measures at both baseline and follow-up identified significant predictors of drinking or abstaining at age 14, including female sex, twin sibling of the opposite sex, accelerated pubertal development, and the twins' assessments, made at age 12, of reduced parental monitoring and a less supportive home atmosphere; drinking at age 14 was also predicted by behaviors rated by the twins' classroom teachers 2 years earlier, increasing with rated behavioral problems but decreasing with rated emotional problems. CONCLUSIONS: Our results show that environmental factors shared by twin siblings account for most of the variance in abstaining or drinking at age 14. We identify predictors of drinking in the adolescent twins' home environments and in their dispositional behaviors, sibling interactions, and pubertal timing.

Sex differences in genetic and environmental factors contributing to body-height.

Sex differences in the heritability of self-reported body-height in two Finnish twin cohorts were studied by using sex-limitation models. The first cohort was born in 1938-1949 (N = 4873 twin pairs) and the second in 1975-1979 (N = 2374 twin pairs). Body-height was greater in the younger cohort (difference of 3.1 cm for men and 2.9 cm for women). The heritability estimates were higher among men (h2 = 0.87 in the older cohort and h2 = 0.82 in the younger cohort) than women (h2 = 0.78 and h2 = 0.67, respectively). Sex-specific genetic factors were not statistically significant in either cohort, suggesting that the same genes contribute to variation in body height for both men and women. The stronger contribution of environmental factors to body-height among women questions the hypothesis that women are better buffered against environmental stress, at least for this phenotype.

Gene-environment interaction in patterns of adolescent drinking: regional residency moderates longitudinal influences on alcohol use.

BACKGROUND: Drinking frequency escalates rapidly during adolescence. Abstinence declines markedly, and drinking monthly or more often becomes normative. Individual differences in adolescent drinking patterns are large, and some patterns are predictive of subsequent drinking problems; little, however, is known of the gene-environment interactions that create them. METHODS: Five consecutive and complete birth cohorts of Finnish twins, born 1975-1979, were enrolled sequentially into a longitudinal study and assessed, with postal questionnaires, at ages 16, 17, and 18.5 years. The sample included 1786 same-sex twin pairs, of whom 1240 pairs were concordantly drinking at age 16. Maximum likelihood models were fit in longitudinal analyses of the three waves of drinking data to assess changes in genetic and environmental influences on alcohol use across adolescence. Secondary analyses contrasted twin pairs residing in rural versus those in urban environments to investigate gene-environment interactions. RESULTS: Longitudinal analyses revealed that genetic factors influencing drinking patterns increased in importance across the 30-month period, and effects arising from common environmental influences declined. Distributions of drinking frequencies in twins residing in urban and rural environments were highly similar, but influences on drinking varied between the two environments. Genetic factors assumed a larger role among adolescents residing in urban areas, while common environmental influences were more important in rural settings. Formal modeling of the data established a significant gene-environment interaction. CONCLUSIONS: The results document the changing impact of genetic and environmental influences on alcohol use across adolescence. Importantly, the results also reveal a significant gene-environment interaction in patterns of adolescent drinking and invite more detailed analyses of the pathways and mechanisms by which environments modulate genetic effects.

Testing between-family associations in within-family comparisons.

Using behaviorally discordant siblings to test for gene-behavior associations is a common tool in molecular genetics, because the within-family contrast offers a research design that avoids confounds inevitable in all between-family comparisons of unrelated individuals. We propose a similar strategy to assess the behavior-behavior associations on which much of psychological science is built. Between-family correlations of personality test scores (e.g., sensation seeking) and behavioral outcomes (e.g., substance use) may be mediated by variables that differ between families (e.g., social class or religiosity) and correlate with both personality and outcome. Contrasting twin and nontwin siblings who were highly discordant for behavioral correlates of substance use, we tested whether between-family behavioral correlations replicated within families. Some, but not all, did. Within-family analyses of behaviorally discordant siblings may find wide application in efforts to clarify the meaning of correlational research data.

Genetic predisposition to organ-specific endpoints of alcoholism.

Medical records of the 15,924 twin-pairs in the National Academy of Sciences-National Research Council (NAS-NRC) twin registry were collected for an additional 16 years through 1994 when the surviving twins were aged 67 to 77 years. Compared with earlier analyses (Hrubec, Z, and Omenn, G. S., Alcohol. Clin. Exp. Res., 5:207-215, 1981), when subjects were aged 51 to 61, there were 23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses of alcoholic psychosis (5.4 per 1,000), and 25% more twins with liver cirrhosis (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses related to alcoholism. Probandwise concordance rates (%) were: alcoholism-26.7 monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis-17.3 MZ, 4.8 DZ (p < 0.05); and cirrhosis-16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.0001). Maximum-likelihood modeling indicated that approximately 50% of the overall variance was due to additive genetic effects; in all diagnosis categories, a totally environmental model gave a significantly poorer fit to the data. Bivariate and trivariate genetic analyses indicated most of the genetic liability for the organ-specific endpoints of psychosis and cirrhosis was due to the shared genetic liability for alcoholism. Once the shared variance with alcoholism was considered, there was no further shared genetic liability for psychosis and cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was significantly greater concordance in MZ twins-pairs for alcoholic psychosis and cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those reported 16 years earlier. In contrast, we found most of the genetic liability to organ-specific complications of alcoholism was shared with the genetic liability for alcoholism per se; only a small portion of the genetic variance of the individual complications was independent of the genetic predisposition for alcoholism.

Genetic influences on human conditionability: a twin study of the conditioned eyeblink response.

Acquisition of the classically conditioned eyeblink response is generally regarded as one of the most basic forms of associative learning. A great deal is known about how the brain encodes this simple form of learning, so that performance of this task may be an indirect indicator of brain functioning. Individual differences in response acquisition have been revealed, but largely ignored, in the research literature. We tested the temporal stability and familial origins of these individual differences using a classic twin study design. Results reveal substantial individual differences in acquisition of the conditioned eyeblink response. These differences are stable across brief retest, and differences in response acquisition exhibit familial aggregation, apparently due, in part, to genetic resemblance.