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Objective: This study was undertaken to clarify how genetic liability and stressful life events interact in the etiology of major depression. Method: Information about stressful life events and onset of major depressive episodes in the past year was collected in a population-based sample of female-female twin pairs including 2,164 individuals, 53,215 person-months of observation, and 492 onsets of depression. Results: Nine 'personal' and three aggregate 'network' stressful events significantly predicted onset of major depression in the month of occurrence, four of which predicted onset with an odds ratio of >10 and were termed 'severe': death of a close relative, assault, serious marital problems, and divorce/breakup. Genetic liability also had a significant impact on risk of onset of depression. For severe stressful events, as well as for 10 of the 12 individual stressful events, the best-fitting model for the joint effect of stressful events and genetic liability on onset of major depression suggested genetic control of sensitivity to the depression-inducing effects of stressful life events. In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively. Linear regression analysis indicated significant Genotype by Environment interaction in the prediction of onset of major depression. Conclusions: Genetic factors influence the risk of onset of major depression in part by altering the sensitivity of individuals to the depression-inducing effect of stressful life events.

Objective: Self-reported symptoms of depression are commonly used in mental health research to assess current psychiatric state, yet wide variation in these symptoms among individuals has been found in both clinical and epidemiologic populations. The authors sought to understand, from a genetic-epidemiologic perspective, the sources of individual differences in depressive symptoms. Method: Self-reported symptoms of depression were assessed in two samples of twins and their spouses, parents, siblings, and offspring: one sample contained volunteer twins recruited through the American Association of Retired Persons and their relatives (N=19,203 individuals) and the other contained twins from a population-based twin registry in Virginia and their relatives (N=11,242 individuals). Model fitting by an iterative, diagonal, weighted least squares method was applied to the 80 different family relationships in the extended twin-family design. Results: Independent analyses of the two samples revealed that the level of depressive symptoms was modestly familial, and familial resemblance could be explained solely by genetic factors and spousal resemblance. The estimated heritability of depressive symptoms was between 30% and 37%. There was no evidence that the liability to depressive symptoms was environmentally transmitted from parents to offspring or was influenced by environmental factors shared either generally among siblings or specifically between twins. With correction for unreliability of measurement, genetic factors accounted for half of the stable variance in depressive symptoms. Conclusions: Depressive symptoms in adulthood partly reflect enduring characteristics of temperament that are substantially influenced by hereditary factors but little, or not at all, by shared environmental experiences in the family of origin.

Objective: The authors seek to understand in general the sources of familial resemblance for alcoholism and in particular how parents transmit the vulnerability to alcoholism to their daughters. Method: The authors interviewed 1,030 pairs of female same-sex twins of known zygosity from the population-based Virginia Twin Registry and 1,468 of their parents. They examined a narrow definition of alcoholism, requiring tolerance or dependence, and a threshold approach that classified individuals either as unaffected or as suffering from one of three levels of severity of alcohol-related problems. Twin-family structural equation models were fitted to the observed tetrachoric or polychoric correlation matrices by using asymptotic weighted least squares. Results: In the best-fitting model from both diagnostic approaches, 1) the familial resemblance for alcoholism was due to genetic factors, with the heritability of liability estimated at 51% to 59%; 2) genetic vulnerability to alcoholism was equally transmitted to daughters from their fathers and from their mothers; and 3) alcoholism in parents was not environmentally transmitted to their children. Assortative mating for alcoholism was found only for the broader definitions of illness. Genetic factors that influenced the liability to alcoholism were the same in the parental and twin generation for the narrow definition of alcoholism. When broader definitions were used, these factors, while substantially correlated, were not identical. Conclusions: The transmission of the vulnerability to alcoholism from parents to their daughters is due largely or entirely to genetic factors.

Objective: The authors develop an exploratory, integrated etiologic model for the prediction of episodes of major depression in an epidemiologic sample of women. Method: Both members of 680 female-female twin pairs of known zygosity from a population-based register were assessed three times at greater than 1-year intervals. The last two assessments included a structured interview evaluation for presence of episodes of major depression, defined by DSM-III-R, in the preceding year. The final structural equation model contained nine predictor variables: genetic factors, parental warmth, childhood parental loss, lifetime traumas, neuroticism, social support, past depressive episodes, recent difficulties, and recent stressful life events. Results: The best-fitting model predicted 50.1% of the variance in the liability to major depression. The strongest predictors of this liability were, in descending order, 1) stressful life events, 2) genetic factors, 3) previous history of major depression, and 4) neuroticism. While 60% of the effect of genetic factors on the liability to major depression was direct, the remaining 40% was indirect and mediated largely by a history of prior depressive episodes, stressful life events, lifetime traumas, and neuroticism. The model suggested that at least four major and interacting risk factor domains are needed to understand the etiology of major depression: traumatic experiences, genetic factors, temperament, and interpersonal relations. Conclusions: Major depression is a multifactorial disorder, and understanding its etiology will require the rigorous integration of genetic, temperamental, and environmental risk factors.

Psychiatric patients are usually asked to note any psychiatric disorders affecting their relatives, especially their first-order relatives. This family history is useful in both psychiatric research and in evaluating the patient, but it must be accurate to be useful. Few studies have examined the characteristics of the person that gives the family history (the informant) which relate to the accuracy of the history. To examine whether a person with a certain psychiatric disorder is more likely to report a family history of the disorder, both twins of 1,033 pairs and one member of 97 pairs were interviewed to find sets of twins in which one twin suffered from either major depression, anxiety disorder, or alcoholism, while the other twin was normal. The discordant twin pairs were then asked whether either their mother or father had the same illness that afflicted one of the twins. Twins that suffered from either major depression or anxiety disorder were significantly more likely to report that one or both parents also had the disorder than were their unafflicted twin siblings. Twins who were alcoholic, on the other hand, were not more likely to report alcoholism among their parents than were their nonalcoholic siblings. These results indicate that psychiatric patients' reports of a family history of their own illness - at least concerning depression or anxiety disorders - should be interpreted cautiously and that other family members may need to be interviewed in order to obtain a more accurate family history. (Consumer Summary produced by Reliance Medical Information, Inc.)

Left ventricular (LV) hypertrophy in adults is a recognized risk factor for the subsequent development of cardiovascular morbidity. To make informed preventive health decisions it is important to understand the interaction of genes and environment on LV mass. In both children and adults, weight is a strong correlate of LV mass. We hypothesized that genetic influences common to both of these variables could in part explain the strong relation between weight and LV mass in children. In a population of 341 twins (11 years old), these questions were asked: (1) How much of the total variance of LV mass is under genetic control? (2) After accounting for weight and weight adjusted for sexual maturity, how much of the remaining variance is genetic? (3) Of the total genetic variance, what proportion is specific for LV mass and what proportion is common to both weight and LV mass? (4) How much of the correlation between these 2 variables is explained by genes common to both LV mass and weight? Univariate genetic analyses documented that genes operating at different magnitudes in boys (63%) and girls (71%) explain a significant proportion of the variance of LV mass. After removing the effect of weight and sexual maturity by regression methods, genes remain an important influence. Bivariate genetic analyses confirmed that genes common to LV mass and weight significantly influence the covariation of these variables and that >90% of the correlation of LV mass and weight is due to common genes. (Am J Cardiol 1991;68:661-668), Left ventricular hypertrophy (enlargement) is generally caused by hypertension, and is a good indication that coronary artery disease will develop. Left ventricular (LV) size increases as body weight increases among adults. In order to make effective recommendations about methods for reducing LV mass, it is necessary to understand the mechanisms regulating it. Because of the association between weight and LV mass, it is likely that genetic factors influence both, but the effects of genetics and the environment are difficult to isolate. A total of 341 pubertal (11-year-old) twins were studied to assess the factors affecting LV mass. The children whose blood pressure was in the upper quintile for their sex and age had greater LV mass. Children in the middle and lower quintiles had normal LV mass. In an earlier study of black twins, the differences in LV mass were greater between dizygotic (fraternal) twins than between monozygotic (identical) twins, and it was concluded that both genetic and environmental factors determined LV mass in black children. In this study univariate genetic analyses demonstrated that genetic influences were responsible for 63 percent of the variance in LV mass in boys and 71 percent in girls. After weight and sexual maturity were removed, genetic factors remained significant. Over 90 percent of the strength of the relation between LV mass and weight was explained by genetic influences. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background: Clinicians and researchers could benefit from a greater understanding of the role of genetic and environmental factors in human eating behavior. Objective: Our aim was to estimate the relative influence of genetic and environmental factors on habitual eating patterns in middle-aged and elderly men and women. Design: Male and female twins (n = 4640) aged [is greater than or equal to] 50 y completed a mailed version of the National Cancer Institute food-frequency questionnaire. Factor analysis was performed to identify eating patterns among respondents. Estimates of genetic, common environmental (shared by family members), and specific environmental (unique to an individual) influences were obtained for food use, serving size, and consumption frequency by comparing monozygotic and dizygotic twin-pair groups with structural equation analysis. Results: Two independent eating patterns were identified: the first consisted of items high in fat, salt, and sugar, and the second reflected healthful eating habits. Although the influence of environmental factors was larger, between 15% and 38% of the total variation in pattern 1 and between 33% and 40% in pattern 2 were explained by genetic influences. Models accounting for sex differences in genetic and environmental estimates fit the data significantly better for food use and serving size of foods in eating pattern 1 and for food use in eating pattern 2. Conclusion: Although 60-85% of the variability in eating patterns was associated with environmental factors, genetic influences were also apparent and there was some evidence of sex specificity. These findings may be important in crafting dietary interventions and predicting adherence to these interventions. Am J Clin Nutr 1999;70:456-65.

Some studies have shown that genetics plays a role in blood pressure and that high-normal infant blood pressure may be the forerunner of adult hypertension. The effects of genetics and environment on blood pressure and heart rate were studied in 251 11-year-old twin pairs. In both sexes, genetic influence could be observed to affect systolic blood pressure, the pressure exerted against the walls of the blood vessels during a heart contraction. Although the amounts of variation of sex-specific genetic effects were the same between the sexes with respect to systolic blood pressure, diastolic pressure (the pressure in between contractions) had a variance of 64 percent among the boys, compared with 51 percent in girls. There were no differences between the sexes with respect to heart rates. There is no firm evidence that a difference in blood pressures exists between boys and girls. No shared environmental effects were noted. (Consumer Summary produced by Reliance Medical Information, Inc.)