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Both normative personality and DSM-IV personality disorders have been found to be heritable. However, there is limited knowledge about the extent to which the genetic and environmental influences underlying DSM personality disorders are shared with those of normative personality. The aims of this study were to assess the phenotypic similarity between normative and pathological personality and to investigate the extent to which genetic and environmental influences underlying individual differences in normative personality account for symptom variance across DSM-IV personality disorders.A large population-based sample of adult twins was assessed for DSM-IV personality disorder criteria with structured interviews at two waves spanning a 10-year interval. At the second assessment, participants also completed the Big Five Inventory, a self-report instrument assessing the five-factor normative personality model. The proportion of genetic and environmental liabilities unique to the individual personality disorder measures, and hence not shared with the five Big Five Inventory domains, were estimated by means of multivariate Cholesky twin decompositions.The median percentage of genetic liability to the 10 DSM-IV personality disorders assessed at wave 1 that was not shared with the Big Five domains was 64%, whereas for the six personality disorders that were assessed concurrently at wave 2, the median was 39%. Conversely, the median proportions of unique environmental liability in the personality disorders for wave 1 and wave 2 were 97% and 96%, respectively.The results indicate that a moderate-to-sizable proportion of the genetic influence underlying DSM-IV personality disorders is not shared with the domain constructs of the Big Five model of normative personality. Caution should be exercised in assuming that normative personality measures can serve as proxies for DSM personality disorders when investigating the etiology of these disorders.

The authors sought to clarify the structure of the genetic and environmental risk factors for 22 DSM-IV disorders: 12 common axis I disorders and all 10 axis II disorders.The authors examined syndromal and subsyndromal axis I diagnoses and five categories reflecting number of endorsed criteria for axis II disorders in 2,111 personally interviewed young adult members of the Norwegian Institute of Public Health Twin Panel.Four correlated genetic factors were identified: axis I internalizing, axis II internalizing, axis I externalizing, and axis II externalizing. Factors 1 and 2 and factors 3 and 4 were moderately correlated, supporting the importance of the internalizing-externalizing distinction. Five disorders had substantial loadings on two factors: borderline personality disorder (factors 3 and 4), somatoform disorder (factors 1 and 2), paranoid and dependent personality disorders (factors 2 and 4), and eating disorders (factors 1 and 4). Three correlated environmental factors were identified: axis II disorders, axis I internalizing disorders, and externalizing disorders versus anxiety disorders.Common axis I and II psychiatric disorders have a coherent underlying genetic structure that reflects two major dimensions: internalizing versus externalizing, and axis I versus axis II. The underlying structure of environmental influences is quite different. The organization of common psychiatric disorders into coherent groups results largely from genetic, not environmental, factors. These results should be interpreted in the context of unavoidable limitations of current statistical methods applied to this number of diagnostic categories.

The authors examined the extent to which two major personality dimensions (extraversion and neuroticism) index the genetic and environmental risk for three phobias (social phobia, agoraphobia, and animal phobia) in twins ascertained from a large, population-based registry.Lifetime phobias and personality traits were assessed through diagnostic interview and self-report questionnaire, respectively, in 7,800 twins from female-female, male-male, and opposite-sex pairs. Sex-limited trivariate Cholesky structural equation models were used to decompose the correlations among extraversion, neuroticism, and each phobia.In the best-fitting models, genetic correlations were moderate and negative between extraversion and both social phobia and agoraphobia, and that between extraversion and animal phobia was effectively zero. Genetic correlations were high and positive between neuroticism and both social phobia and agoraphobia, and that between neuroticism and animal phobia was moderate. All of the genetic risk factors for social phobia and agoraphobia were shared with those that influence extraversion and neuroticism; in contrast, only a small proportion of the genetic risk factors for animal phobia (16%) was shared with those that influence personality. Shared environmental experiences were not a source of correlations between personality traits and phobias, and unique environmental correlations were relatively modest.Genetic factors that influence individual variation in extraversion and neuroticism appear to account entirely for the genetic liability to social phobia and agoraphobia, but not animal phobia. These findings underline the importance of both introversion (low extraversion) and neuroticism in some psychiatric disorders.

Objective: The authors sought to determine whether, in a general population sample, different categories of adverse life events were associated with different patterns of depressive symptoms. Method: A total of 4,856 individuals (53% female) who experienced depressive symptoms in the previous year were assessed in up to four waves over a maximum of 12 years. At each wave, participants reported the severity of 12 symptoms disaggregated from the nine DSM-III-R criteria for major depression and the self-identified cause of these symptoms, which were classified into nine categories of adverse life events. Results: The patterns of depressive symptoms associated with the nine categories of adverse life events differed significantly. Deaths of loved ones and romantic breakups were marked by high levels of sadness, anhedonia, appetite loss, and (for romantic breakups) guilt. Chronic stress and, to a lesser degree, failures were associated with fatigue and hypersomnia, but less so with sadness, anhedonia, and appetite loss. Those who reported that no adverse life events caused their dysphoric episodes reported fatigue, appetite gain, and thoughts of self-harm, but less sadness or trouble concentrating. These symptom patterns were found in a between-persons analysis of participants who had a single dysphoric episode, and they were replicated in an independent within-persons analysis of episode-specific symptom deviations among individuals with multiple episodes. Similar results were obtained when the sample was restricted to those meeting DSM-III-R diagnostic criteria for major depression. Conclusions: Depression is a pathoplastic syndrome. Different types of life events are related to different depressive symptom profiles. The results from the withinpersons analysis suggest that these relationships are causal.

Objective: The anxiety and depressive disorders exhibit high levels of lifetime comorbidity with one another. The authors examined how genetic and environmental factors shared by the personality trait neuroticism and seven internalizing disorders may help explain this comorbidity. Method: Lifetime major depression, generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal phobia, situational phobia, and neuroticism were assessed in over 9,000 twins from male-male, female-female, and oppositesex pairs through structured diagnostic interviews. Multivariate structural equation models were used to decompose the correlations between these phenotypes into genetic and environmental components, allowing for sex-specific factors. Results: Genetic factors shared with neuroticism accounted for between one-third and one-half of the genetic risk across the internalizing disorders. When nonsignificant gender differences were removed from the models, the genetic correlations between neuroticism and each disorder were high, while individual-specific environmental correlations were substantially lower. In addition, the authors could identify a neuroticism-independent genetic factor that significantly increased risk for major depression, generalized anxiety disorder, and panic disorder. Conclusions: There is substantial, but not complete, overlap between the genetic factors that influence individual variation in neuroticism and those that increase liability across the internalizing disorders, helping to explain the high rates of comorbidity among the latter. This may have important implications for identifying the susceptibility genes for these conditions.

Objective: Impairment was added as a diagnostic criterion for many psychiatric disorders in DSM-IV. Does the addition of impairment influence only prevalence rates, or does it also introduce new etiological factors into psychiatric diagnoses? Method: A lifetime history of major depression and associated functional impairment was assessed by personal interview with 3,669 female and 4,377 male twins from the population-based Virginia Twin Registry. Structural equation modeling was used to estimate the correlation between risk factors for major depression and associated functional impairment. Results: While the risk factors for major depression and associated functional impairment are substantially correlated, they are not identical. The most parsimonious model suggests that over a quarter of the variance in associated functional impairment is due to factors unrelated to risk for major depression. Of the variance unique to associated functional impairment, approximately one-third is familial. The relationship between associated functional impairment and major depression did not differ significantly between men and women. Conclusions: Risk factors for major depression and associated functional impairment are substantially but imperfectly correlated. The addition of associated functional impairment as a criterion for the diagnosis of major depression not only lowers prevalence estimates but also introduces a small set of new etiological factors into the diagnosis of major depression.

Data on use and misuse of six classes of illicit substances by male twin pairs were used to examine whether genetic and shared environmental risk factors for substance use disorders are substance-specific or -nonspecific in their effect.Lifetime history of use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates was assessed at personal interview in both members of 1,196 male-male twin pairs ascertained by the Virginia Twin Registry. Multivariate twin modeling of substance-nonspecific (common) and substance-specific genetic, shared environmental, and unique environmental risk factors was performed by using the program Mx.High levels of comorbidity involving the different substance categories were observed for both use and abuse/dependence. One common genetic factor was found to have a strong influence on risk for illicit use and abuse/dependence for all six substance classes. A modest influence of substance-specific genetic factors was seen for use but not for abuse/dependence. Shared environmental factors were more important for use than for abuse/dependence and were mediated entirely through a single common factor.In an adult population-based sample of male twins, both the genetic and the shared environmental effects on risk for the use and misuse of six classes of illicit substances were largely or entirely nonspecific in their effect. Environmental experiences unique to the person largely determine whether predisposed individuals will use or misuse one class of psychoactive substances rather than another.

The authors conducted a meta-analysis of relevant data from primary studies of the genetic epidemiology of major depression.The authors searched MEDLINE and the reference lists of previous review articles to identify relevant primary studies. On the basis of a review of family, adoption, and twin studies that met specific inclusion criteria, the authors derived quantitative summary statistics.Five family studies met the inclusion criteria. The odds ratios for proband (subjects with major depression or comparison subjects) versus first-degree relative status (affected or unaffected with major depression) were homogeneous across the five studies (Mantel-Haenszel odds ratio=2.84, 95% CI=2.31-3.49). No adoption study met the inclusion criteria, but the results of two of the three reports were consistent with genetic influences on liability to major depression. Five twin studies met the inclusion criteria, and their statistical summation suggested that familial aggregation was due to additive genetic effects (point estimate of heritability of liability=37%, 95% CI=31%-42%), with a minimal contribution of environmental effects common to siblings (point estimate=0%, 95% CI=0%-5%), and substantial individual-specific environmental effects/measurement error (point estimate=63%, 95% CI=58%-67%). The literature suggests that recurrence best predicts the familial aggregation of major depression.Major depression is a familial disorder, and its familiality mostly or entirely results from genetic influences. Environmental influences specific to an individual are also etiologically significant. Major depression is a complex disorder that does not result from either genetic or environmental influences alone but rather from both. These findings are notably consistent across samples and methods and are likely to be generally applicable.

OBJECTIVE: The authors sought to derive heritability estimates for anorexia nervosa and to explore the etiology of the comorbid relationship between anorexia nervosa and major depression. METHOD: They applied bivariate structural equation modeling to a broad definition of anorexia nervosa and lifetime major depression as assessed in a population-based sample of 2,163 female twins. RESULTS: Anorexia nervosa was estimated to have a heritability of 58% (95% confidence interval=33%–84%). The authors were unable to completely rule out a contribution of shared environment. The comorbidity between anorexia nervosa and major depression is likely due to genetic factors that influence the risk for both disorders. CONCLUSIONS: Although the study was limited by the small number of affected twins, the results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexia nervosa and major depression.

While family and twin studies suggest that retrospectively reported premenstrual symptoms are heritable, these studies have not accounted for the unreliability of such measures. In addition, we know little about the relationship of the familial risk factors for premenstrual symptoms and major depression.Lifetime major depression and premenstrual-related tiredness, sadness, and irritability were assessed twice over 6 years in 1,312 menstruating female twins ascertained from a population-based twin register. A twin-measurement model--which permits estimation of the etiologic roles of genetic and environmental factors with correction for errors of measurement or short-term temporal fluctuations--was applied to these data.A single premenstrual symptom factor was found that was moderately stable over time. The best-fitting twin-measurement model estimated the heritability of the stable component of premenstrual symptoms at 56% and showed no impact of family-environmental factors. A bivariate twin-measurement model estimated that the genetic and environmental risk factors for lifetime major depression contributed only modestly to the etiology of premenstrual syndrome. No evidence was found for significant biases in the twin method.Retrospectively reported premenstrual-related symptoms of depression and anxiety are moderately stable over time and, when correction is made for this level of stability, substantially heritable. The genetic and environmental risk factors for these premenstrual symptoms and lifetime major depression are not closely related.

Objective: The authors sought to evaluate whether the pattern ofschizophrenia and related disorders in probands and their relatives can be explained by a single underlying continuum ofliability to the “schizophrenia spectrum. “ Method: In the epidemiologically based Roscommon Family Study, the authors separately examined-in siblings, parents, and relatives of index and comparison probands-the familial aggregation and coaggregation offive hierarchically defined disorders: schizophrenia, schizoaffective disorder, schizotypal/paranoid personality disorder, other nonaffective psychoses, and psychotic affective illness. A multiple threshold model was fitted to these contingency tables by maximum likelihood. Results: The multiple threshold model that constrained resemblance to be the same in siblings and parents fit the data well and estimated the correlation in liability to schizophrenia spectrum disorders between probands and first-degree relatives at 0.36. Parents, however, required higher levels of liability to manifest schizophrenia spectrum disorders than siblings. While schizophrenia and psychotic affective illness could be clearly assigned to the two extremes ofthe schizophrenia spectrum, the proper ordering ofschizoaffective disorder, schizotypal/paranoid personality disorder, and other nonaffective psychoses could not be unambiguously determined. Conclusions: These results are consistent with the existence of a schizophrenia spectrum in which these five disorders are manifestations, of varying severity, of the same underlying vulnerability. This vulnerability is strongly transmitted within families. (Am J Psychiatry 1995; 152:749-754)

Objective: Self-reported symptoms of depression are commonly used in mental health re­ search to assess current psychiatric state, yet wide variation in these symptoms among indi­ viduals 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 rela­ tives (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 in­ fluenced by environmental factors shared either generally among siblings or specifically be­ tween 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 influ­ enced by hereditary factors but little, or not at all, by shared environmental experiences in the family of origin. (Am] Psychiatry 1994; 151:1605-1614)

Objective: The authors seek to understand in general the sources of familial resemblance f or alcoholism and in particular how parents transmit the vulnerability to alcoholism to their daughters. Method: The authors interviewed 1,030 pairs offemale same-sex twins of known zygosity from the population-based Virginia Twin Registry and 1,468 oftheir parents. They examined a narrow definition ofalcoholism, 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 f itted 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.

OBJECTIVE The authors seek to clarify, from both an epidemiologic and genetic perspective, the major risk factors for bulimia nervosa and to understand the relationship between narrowly defined bulimia and bulimia-like syndromes. METHOD Personal structured psychiatric interviews were conducted with 2,163 female twins from a population-based register. Psychiatric disorders were assessed using DSM-III-R criteria. RESULTS Lifetime prevalence and risk for narrowly defined bulimia were 2.8% and 4.2%, respectively. Including bulimia-like syndromes increased these estimates to 5.7% and 8.0%, respectively. Risk factors for bulimia included 1) birth after 1960, 2) low paternal care, 3) a history of wide weight fluctuation, dieting, or frequent exercise, 4) a slim ideal body image, 5) low self-esteem, 6) an external locus of control, and 7) high levels of neuroticism. Significant comorbidity was found between bulimia and anorexia nervosa, alcoholism, panic disorder, generalized anxiety disorder, phobia, and major depression. Proband-wise concordance for narrowly defined bulimia was 22.9% in monozygotic and 8.7% in dizygotic twins. The best-fitting model indicated that familial aggregation was due solely to genetic factors with a heritability of liability of 55%. A multiple threshold model indicated that narrowly defined bulimia nervosa and bulimia-like syndromes represented different levels of severity on the same continuum of liability. CONCLUSIONS The liability to fully syndromal bulimia nervosa, which affects around one in 25 women at some point in their lives, is substantially influenced by both epidemiologic and genetic risk factors. The same factors that influence the risk for narrowly defined bulimia also influence the risk for less severe bulimia-like syndromes.