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ABSTRACT: Cannabis and other illicit drugs are often used or abused comorbidly. Two competing theories to explain this comorbidity are (i) the phenotypic causation (gateway) model and (ii) the correlated liabilities model. We used data from 1191 male and 934 female same-sex twin pairs to test 13 genetically informative models of comorbidity. Models were fit separately for use and abuse/dependence in both sexes. The correlated liabilities model provided a good fit to the data for cannabis and other illicit drug use, as well as abuse/dependence. The relationship between the use or abuse of cannabis and other illicit drugs is not entirely phenotypic, as depicted by the random multiformity of cannabis model, which is an adaptation of the gateway model. The comorbidity appears to arise from correlated genetic and environmental influences. There is some evidence for a model in which high-risk cannabis users may be at increased risk for other illicit drug use. For abuse/dependence, a model with causal pathways between the liability for cannabis and other illicit drug abuse/dependence also fits well. Overall, our results suggest that the use and abuse/dependence of cannabis and other illicit drugs are strongly linked via common risk factors that jointly influence their individual liabilities.
Behavior Genetics 06/2004; 34(3):217-28. · 2.52 Impact Factor
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ABSTRACT: Depressive symptoms reflect depressed mood over a relatively short period of time and are measured using symptom checklists such as the SCL-90. There is some evidence that depressive symptoms are associated with major depression (MD), which is a clinically diagnosed psychiatric illness. Genetic studies of depressive symptomatology suggest a role for genetic factors as well as unique environmental influences. While epidemiological research suggests that depressive symptoms may be influenced by sex-specific factors, few genetically informative findings support this result entirely. We used data from male and female same sex and opposite-sex twin pairs to assess the extent to which genetic, shared and unique environmental factors influence depressive symptoms. Furthermore, we tested for the presence of qualitative and quantitative sex differences in depressive symptoms. Our results suggest that similar to other studies, depressive symptomatology is moderately heritable (31%) with no evidence for shared environmental factors. Our best fitting model suggests that there are no qualitative or quantitative sex differences in depressive symptoms. Our analyses suggest that while there may be mean differences in the levels of depressive symptoms across sexes, the genetic and environmental factors that predispose males and females to depressive symptoms are not different.
Twin Research 05/2004; 7(2):176-81.
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ABSTRACT: Three potent risk factors for major depression are female sex, the personality trait of neuroticism, and adversity resulting from exposure to stressful life events. Little is known about how they interrelate in the etiology of depressive illness.
In over 7,500 individual twins from a population-based sample, the authors used a Cox proportional hazard model to predict onsets of episodes of DSM-III-R major depression in the year before the latest interviews on the basis of previously assessed neuroticism, sex, and adversity during the past year; adversity was operationalized as the long-term contextual threat scored from 15 life event categories.
In the best-fit Cox model for prediction of depressive onsets, neuroticism, female sex, and greater adversity all strongly increased risk for major depression. An interaction was seen between neuroticism and adversity such that individuals with high neuroticism were at greater overall risk for major depression and were more sensitive to the depressogenic effects of adversity. An interaction was also seen between adversity and sex, as the excess risk for major depression in women was confined to individuals with low stress exposure.
Psychosocial adversity interacts both with neuroticism and with sex in the etiology of major depression. The impact of neuroticism on illness risk is greater at high than at low levels of adversity, while the effect of sex on probability of onset is the opposite--greater at low than at high levels of stress. Complete etiologic models for major depression should incorporate interactions between risk factor classes.
American Journal of Psychiatry 05/2004; 161(4):631-6. · 12.54 Impact Factor
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ABSTRACT: The examination of opposite-sex and same-sex dizygotic twins allows us to explore the sex-specific comorbidity of psychiatric disorders. To date, this question has not been explored in eating disorders.
To determine whether sex influences shared risk factors between bulimia nervosa (BN) and other forms of psychopathology.
The study examines associations between BN and other forms of psychopathology in twin pairs using interview and survey reports.
Twins from the Virginia population-based twin registry.
Male-female dizygotic twins (N = 1192 pairs), mean (SD) age 36.6 (8.9) years, and female-female dizygotic twins (N = 467 pairs), mean (SD) age 36.0 (7.6) years.
Lifetime psychiatric disorders as diagnosed by a structured psychiatric interview, including major depression, anxiety disorders, and substance abuse and dependence. Also, continuous measures of body mass index and personality, including neuroticism and novelty seeking.
Significant within-person associations existed for women between BN and higher body mass index, neuroticism, novelty seeking, and all lifetime psychopathology. Results from this study suggest the presence of either familial or nonfamilial shared risk factors between BN and generalized anxiety disorder, neuroticism, psychoactive substance use, novelty seeking, major depression, and panic disorder. The shared risk factors between BN and generalized anxiety disorder and BN and novelty seeking were only present in men.
Evidence supports the existence of a sex-specific manifestation of familial liability with respect to BN and generalized anxiety disorder and BN and novelty seeking.
Archives of General Psychiatry 04/2004; 61(3):251-6. · 12.02 Impact Factor
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ABSTRACT: The roles of genetic and environmental influences on stressful life events were examined in 3938 twin pairs (MZ, same-sex DZ, and opposite-sex DZ) using a sex-limitation model. Life events were assessed by personal interview, and were categorized as being either personal (i.e., events that occur directly to the individual) or network (i.e., events that occur to someone within the individual's social network, thus affecting the individual indirectly). Consistent with previous reports, genetic factors were found to exert more influence on personal events than network events. Genetic correlations between males and females suggest that many of the same genetic factors are acting within both genders.
Twin Research 03/2004; 7(1):33-8.
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Carol A Prescott
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ABSTRACT: Historically, the focus of behavior genetic research was to obtain estimates of the sources of familial resemblance for a single phenotype. Current research strategies have moved beyond heritability estimates to the search for physiological and behavioral mechanisms by which genetic risk is translated into individual differences in behavior and disease liability. Such research questions often require multivariate designs and complex analytic models, including the analysis of continuous and categorical dependent variables within the same model. Recent advances in computer software for categorical data analysis have increased the tools available for researchers in behavior genetics. This paper describes how to use the Mplus software program (Muthén and Muthén, 1998, 2002) for the analysis of data obtained from twins. Example analyses include two- and five-group twin models for univariate and bivariate continuous and categorical variables. Data on alcoholism and age at first drink drawn from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders are used to illustrate how Mplus can be used to analyze multiple-category variables, recode and transform variables, select subgroups for analysis, handle subjects with incomplete data, include constraints to ensure non-negative loadings, include model covariates, model sex differences, and test alternative hypotheses about mediation of genetic risk by measured variables.
Behavior Genetics 02/2004; 34(1):17-40. · 2.52 Impact Factor
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ABSTRACT: Individual differences in motivations to drink have been proposed as a mechanism that mediates risk for alcoholism. We investigated the genetic and environmental sources of variation in motivations for drinking, as assessed by four scales of the Alcohol Use Inventory (AUI), and then examined the extent to which genetic and environmental variations in risk for alcoholism are mediated by individual differences in drinking motives.
Data on four AUI scales (assessing drinking to manage mood states, to relieve social anxiety, in social situations, and to improve mental functioning) and lifetime DSM-IV alcohol abuse and/or dependence (AAD) were obtained from 2529 female and 3709 male adult twins, including 2229 complete twin pairs, from the population-based Virginia Twin Registry.
Logistic regression analyses indicated that higher scores on each of the four AUI variables were significantly associated with AAD, with increases in risk for diagnosis of 40% to 141% per standard deviation increase in AUI score. Structural modeling analyses conducted using Mplus indicated that individual differences in AUI scores were in part due to genetic variation, particularly among women. Among males, genetic factors were substantial for drinking to alter mood but small for other measures. A substantial portion of the genetic variation in AAD overlapped with drinking to manage mood states. Results from bivariate twin models of AAD and the AUI scales were consistent with the mediation hypothesis for the social anxiety and social interaction scales but not drinking to manage mood or to enhance mental functioning.
Genetic contributions to variation in risk for alcoholism may be mediated in part by individual differences in motivations related to drinking in social settings. Drinking to manage mood indexes genetic risk for alcoholism but does not appear to act as a direct cause of alcoholism.
Alcoholism Clinical and Experimental Research 02/2004; 28(1):29-39. · 3.34 Impact Factor
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ABSTRACT: 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?
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.
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.
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.
American Journal of Psychiatry 01/2004; 160(12):2128-33. · 12.54 Impact Factor
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ABSTRACT: Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women.
Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx.
We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia.
The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.
Archives of General Psychiatry 10/2003; 60(9):929-37. · 12.02 Impact Factor
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ABSTRACT: Although substantial evidence suggests that stressful life events predispose to the onset of episodes of depression and anxiety, the essential features of these events that are depressogenic and anxiogenic remain uncertain.
High contextual threat stressful life events, assessed in 98 592 person-months from 7322 male and female adult twins ascertained from a population-based registry, were blindly rated on the dimensions of humiliation, entrapment, loss, and danger and their categories. Onsets of pure major depression (MD), pure generalized anxiety syndrome (GAS) (defined as generalized anxiety disorder with a 2-week minimum duration), and mixed MD-GAS episodes were examined using logistic regression.
Onsets of pure MD and mixed MD-GAS were predicted by higher ratings of loss and humiliation. Onsets of pure GAS were predicted by higher ratings of loss and danger. High ratings of entrapment predicted only onsets of mixed episodes. The loss categories of death and respondent-initiated separation predicted pure MD but not pure GAS episodes. Events with a combination of humiliation (especially other-initiated separation) and loss were more depressogenic than pure loss events, including death. No sex differences were seen in the prediction of episodes of illness by event categories.
In addition to loss, humiliating events that directly devalue an individual in a core role were strongly linked to risk for depressive episodes. Event dimensions and categories that predispose to pure MD vs pure GAS episodes can be distinguished with moderate specificity. The event dimensions that preceded mixed MD-GAS episodes were largely the sum of those that preceded pure MD and pure GAS episodes.
Archives of General Psychiatry 09/2003; 60(8):789-96. · 12.02 Impact Factor
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ABSTRACT: 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.
American Journal of Psychiatry 05/2003; 160(4):687-95. · 12.54 Impact Factor
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ABSTRACT: The role of religion in mental illness remains understudied. Most prior investigations of this relationship have used measures of religiosity that do not reflect its complexity and/or have examined a small number of psychiatric outcomes. This study used data from a general population sample to clarify the dimensions of religiosity and the relationships of these dimensions to risk for lifetime psychiatric and substance use disorders.
Responses to 78 items assessing various aspects of broadly defined religiosity were obtained from 2,616 male and female twins from a general population registry. The association between the resulting religiosity dimensions and the lifetime risk for nine disorders assessed at personal interview was evaluated by logistic regression. Of these disorders, five were "internalizing" (major depression, phobias, generalized anxiety disorder, panic disorder, and bulimia nervosa), and four were "externalizing" (nicotine dependence, alcohol dependence, drug abuse or dependence, and adult antisocial behavior).
Seven factors were identified: general religiosity, social religiosity, involved God, forgiveness, God as judge, unvengefulness, and thankfulness. Two factors were associated with reduced risk for both internalizing and externalizing disorders (social religiosity and thankfulness), four factors with reduced risk for externalizing disorders only (general religiosity, involved God, forgiveness, and God as judge), and one factor with reduced risk for internalizing disorders only (unvengefulness).
Religiosity is a complex, multidimensional construct with substantial associations with lifetime psychopathology. Some dimensions of religiosity are related to reduced risk specifically for internalizing disorders, and others to reduced risk specifically for externalizing disorders, while still others are less specific in their associations. These results do not address the nature of the causal link between religiosity and risk for illness.
American Journal of Psychiatry 04/2003; 160(3):496-503. · 12.54 Impact Factor
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ABSTRACT: Gender differences in the symptoms of major depression have received limited research attention. The aim of this study was to explore these differences in male-female twin pairs.
Telephone interviews were conducted to determine the lifetime history of major depression in 1,404 complete pairs of opposite-sex dizygotic twins identified through a population-based registry. From these, the authors selected 201 pairs in which both twins fulfilled the DSM-III-R criteria for lifetime major depression. Dichotomous symptom variables were analyzed by using McNemar's chi-square. For continuous variables, conditional logistic regression was used.
Female twins reported experiencing significantly more fatigue, hypersomnia, and psychomotor retardation during the most severe major depressive episode, whereas male twins reported more insomnia and agitation.
In this group of matched twins, gender differences in the symptoms of major depression were seen in the areas of sleep, psychomotor changes, and fatigue. Gender significantly modifies some clinical features of major depression.
American Journal of Psychiatry 09/2002; 159(8):1427-9. · 12.54 Impact Factor
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ABSTRACT: Major depression is a multifactorial disorder with many etiologic variables that are interrelated through developmental pathways. The authors used structural equation modeling to generate a developmental model for the etiology of major depression in women.
Data from 1,942 adult female twins, interviewed up to four times over a 9-year period, were used to construct a developmental model to predict depressive episodes in the year before the most recent interview. Eighteen risk factors in five developmental tiers were considered: 1) childhood (genetic risk, disturbed family environment, childhood sexual abuse, and childhood parental loss), 2) early adolescence (neuroticism, self-esteem, and early-onset anxiety and conduct disorder), 3) late adolescence (educational attainment, lifetime traumas, social support, and substance misuse), 4) adulthood (history of divorce and past history of major depression), and 5) the last year (marital problems, difficulties, and stressful life events).
The best fitting model included six correlations and 64 paths, provided an excellent fit to the data, and explained 52% of the variance in liability to episodes of major depression. The findings suggest that the development of risk for major depression in women results from three broad pathways reflecting internalizing symptoms, externalizing symptoms, and psychosocial adversity.
Major depression is an etiologically complex disorder, the full understanding of which will require consideration of a broad array of risk factors from multiple domains. These results, while plausible, should be treated with caution because of problems with causal inference, retrospective recall bias, and the limitations of a purely additive statistical model.
American Journal of Psychiatry 08/2002; 159(7):1133-45. · 12.54 Impact Factor
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ABSTRACT: The subtypes of major depression (MD) remain incompletely understood. While there is consensus about the existence of MD with 'typical' vegetative features, further data are required to evaluate the existence of MD with atypical features.
Assessment of MD symptomatology in year prior to interview was available in 6846 individual twins from a population-based twin registry. The nine 'A' criteria for DSM-IV MD were unpacked so that the nature of sleep disturbance, appetite and weight changes, and motoric alterations were recorded. Latent class analysis was used to create an empirical typology of MD.
Seven latent classes appeared to provide the best representation of the data. The most severe of these classes had interpretable profiles corresponding to typical MD, atypical MD, and 'minor' but seemingly important depressive states. These classes were generally more deviant than a comparison group for nearly all available validators. There tended to be a gradient with the typical class being most extreme, minor depressive classes the least extreme, and the atypical class having an intermediate position.
Our findings support the existence of atypical depression as a phenomenological subtype of MD. Besides the differences in symptom patterns, there are many more similarities than differences across a range of external validators. Similar to other reports, we found evidence of the importance and morbidity of depressive symptomatology that does not meet the DSM-IV MD thresholds.
Journal of Affective Disorders 05/2002; 68(2-3):273-84. · 3.52 Impact Factor
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ABSTRACT: We evaluated for phobias the prediction of the stress-diathesis model that the magnitude of stress at onset is inversely proportional to the level of underlying diathesis.
In more than 7500 twins from a population-based registry, we assessed the personality trait of neuroticism--as an index of phobia-proneness--and the lifetime histories of 5 phobia subtypes (agoraphobia, social, animal, situational, and blood or injury) and their associated irrational fears. Interviewers classified the mode of acquisition of the fear in phobic twins into 5 possible categories: trauma to self (further divided by severity), observed trauma to others, observed fear in others, taught by others to be afraid, and no memory of how or why fear developed. Analyses were conducted by logistic regression and analysis of covariance.
The mode of acquisition had moderate test-retest reliability and differed meaningfully across phobia subtypes. None of the 3 tests of the stress-diathesis model was confirmatory: (1) the risk of phobias was not elevated in co-twins of twins who had no memory of their mode of acquisition, (2) the risk of phobias was not decreased in co-twins of twins who had severe trauma to self, and (3) no significant relationship, in phobic twins, was found between levels of neuroticism and mode of acquisition.
These results are inconsistent with the traditional etiologic theories for phobias, which assume conditioning or social transmission. However, they are compatible with nonassociative models, which postulate that the vulnerability to phobias is largely innate and does not arise directly from environmental experiences. The stress-diathesis model may not be an appropriate paradigm for phobic disorders.
Archives of General Psychiatry 04/2002; 59(3):242-8. · 12.02 Impact Factor
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Carol A Prescott
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ABSTRACT: One of the characteristics influencing a person's risk for alcoholism is his or her sex, and various factors may contribute to sex differences in risk. Adoption studies have provided some evidence of possible sex differences in the heritability of alcoholism, but overall the findings have been inconclusive. Twin studies have consistently supported the role of genetic risk factors in the heritability of alcoholism in men, and shared environmental factors also play a role in the familiality of alcoholism among women. In addition, sex differences exist in the patterns of transmission of alcoholism between family members. However, the genetic epidemiology research conducted to date on this issue has several limitations, some of which may be resolved by future molecular genetic studies.
Alcohol research & health: the journal of the National Institute on Alcohol Abuse and Alcoholism 02/2002; 26(4):264-73. · 0.58 Impact Factor
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ABSTRACT: The present study uses a population-based sample of 6.806 adult twins from same-sex and opposite-sex twin pairs to examine sex differences in the underlying genetic and environmental architecture of the development of antisocial behavior (AB). Retrospective reports of AB during three different developmental periods were obtained: prior to age 15 years (childhood), age 15-17 years (adolescent), and age 18 years and older (adult). Structural equation modeling analyses revealed that there was no evidence for sex-specific genetic or sex-specific shared family environmental influences on the development of AB; that is, the types of genetic and environmental influence were similar for males and females. For both sexes, a model that allowed for genetic influences on adolescent and adult AB that were not shared with childhood AB fit better than a model with a single genetic factor. In contrast, shared environmental influences on adolescent and adult AB overlapped entirely with shared environmental influences on childhood AB. Genetic factors played a larger role in variation in childhood AB among females, whereas shared environmental factors played a larger role among males. However, heritability of AB increased from childhood to adolescence and adulthood for both sexes, and the magnitude of genetic and environmental influences on adolescent and adult AB was approximately equal across sex. We speculate that sex differences in timing of puberty may account for the earlier presence of genetic effects among females.
Development and Psychopathology 02/2002; 14(2):395-416. · 4.40 Impact Factor
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ABSTRACT: Obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS) exhibit a familial pattern of transmission. The different components of these conditions and the extent to which these components are inherited have not been studied well. A sample of 1,054 female twins, including both members of 527 pairs, from the Virginia Twin Registry returned questionnaires that included 20 items from the Padua Inventory of obsessive-compulsiveness. Their responses were used to estimate the heritability of the different factors of OCS in this population. Principal components analysis suggested two meaningful factors corresponding roughly to obsessions and compulsions. The best-fit model suggested heritabilities of 33 and 26%, respectively. The correlation between additive genetic effects on compulsiveness and obsessiveness was found to be +0.53. Self-report symptoms of obsessions and compulsions in women from the general population are moderately heritable and due, in part, to the same genetic risk factors. An understanding of the etiology of these symptoms is relevant to the study of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:791–796, 2000. © 2000 Wiley-Liss, Inc.
American Journal of Medical Genetics 12/2000; 96(6):791 - 796.
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ABSTRACT: Although familial factors have been shown to influence drug use, abuse, and dependence, little is known about the common and specific factors that influence polysubstance use and misuse. Our objective was to assess whether there are genetic and environmental factors specific to each substance or whether there are factors that predispose an individual to use of illicit substances in general. Twins from female-female pairs from the Virginia Twin Registry were interviewed by phone to assess lifetime nonmedical use of cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Multivariate, biometrical model-fitting was applied to the data using the Mx computer package. In the best-fitting model, use of all classes of drugs was influenced by a single general genetic factor (common to all substances) and a general familial environmental factor. The magnitude of influence of the general genetic factor ranged from 3% of the variance for opiates to 59% of the variance for cannabis. Some differences were seen from the univariate results, indicating some of the parameter estimates were unstable due to small numbers of concordant pairs. However, generalizations could be made. In women, the substances examined share genetic and familial environmental factors which contribute to the vulnerability to use. Degree of influence of the factors differs for the substances examined. However, no specific genetic or familial environmental factors were found to contribute significantly to use of any of the illicit substances. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:665–670, 2000. © 2000 Wiley-Liss, Inc.
American Journal of Medical Genetics 10/2000; 96(5):665 - 670.
