Biomedical subjects

Charles O Gardner

Publications and source records attributed to Charles O Gardner.

17 recordsLinked to original sources

PubMed2006

The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample.

BACKGROUND: Prior studies report high levels of co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) and suggest that these disorders are closely related genetically. The personality trait of neuroticism (N) is substantially correlated with risk for MD and GAD. METHOD: Bivariate twin models were applied to lifetime diagnoses of modified DSM-IV diagnosis of MD and GAD obtained at personal interview in 1998-2003 with 37296 twins from the population-based Swedish Twin Registry. A trivariate Cholesky model with N, MD and GAD was applied to a subset (23280 members of same-sex twin pairs) who completed a self-report questionnaire assessing N in 1972-1973. RESULTS: In the best-fit bivariate model, the genetic correlation between MD and GAD was estimated at +1.00 in females and +0.74 in males. Individual-specific environmental factors were also shared between the two disorders with an estimated correlation of +0.59 in males and +0.36 in females. In the best-fit trivariate Cholesky model, genetic factors indexed by N impacted equally on risk for MD and GAD in males and females. However, in both sexes, genetic risk factors indexed by N contributed only around 25% to the genetic correlation between MD and GAD. CONCLUSION: Genetic risk factors for lifetime MD and GAD are strongly correlated, with higher correlations in women than in men. Although genetic risk factors indexed by the personality trait of N contribute substantially to risk for both MD and GAD, the majority of genetic covariance between the two disorders results from factors not shared with N.

Adult↗

PubMed2006

Caffeine intake, toxicity and dependence and lifetime risk for psychiatric and substance use disorders: an epidemiologic and co-twin control analysis.

BACKGROUND: Although caffeine is the most commonly used psychoactive substance and often produces symptoms of toxicity and dependence, little is known, especially in community samples, about the association between caffeine use, toxicity and dependence and risk for common psychiatric and substance use disorders. METHOD: Assessments of lifetime maximal caffeine use and symptoms of caffeine toxicity and dependence were available on over 3600 adult twins ascertained from the population-based Virginia Twin Registry. Lifetime histories of major depression (MD), generalized anxiety disorder (GAD) and panic disorder, alcohol dependence, adult antisocial behavior and cannabis and cocaine abuse/dependence were obtained at personal interview. Logistic regression analyses in the entire sample and within monozygotic (MZ) twin pairs were conducted in SAS. RESULTS: In the entire sample, measures of maximal caffeine use, heavy caffeine use, and caffeine-related toxicity and dependence were significantly and positively associated with all seven psychiatric and substance use disorders. However, within MZ twin pairs, controlling for genetic and family environmental factors, these associations, while positive, were all non-significant. These results were similar when excluding twins who denied regular caffeine use. CONCLUSIONS: Maximal lifetime caffeine intake and caffeine-associated toxicity and dependence are moderately associated with risk for a wide range of psychiatric and substance use disorders. Analyses of these relationships within MZ twin pairs suggest that most of the observed associations are not causal. Rather, familial factors, which are probably in part genetic, predispose to both caffeine intake, toxicity and dependence and the risk for a broad array of internalizing and externalizing disorders.

Adult↗

PubMed2006

The temporal relationship of the onsets of alcohol dependence and major depression: using a genetically informative study design.

BACKGROUND: Although alcohol dependence (AD) and major depression (MD) are highly co-morbid, their causal relationship is unclear. In this longitudinal study, we used a genetically informative population-based twin sample to examine the age-at-onset distributions and the temporal relationship of AD and MD. METHOD: Our sample included 7477 twins, whose diagnoses of AD and MD and age-at-onset information were obtained from structured interviews. Individual-level survival analyses were conducted based on 2603 monozygotic (MZ) twins, and co-twin diagnosis was included in models as an index of familiar liability to AD and MD. RESULTS: The age-at-onset distributions of AD and MD differed substantially. Most onsets of AD were in young adulthood, whereas MD had a flatter distribution across age. Most subjects, especially women, had an onset of MD preceding AD. Prior MD significantly affected risk for developing AD, and this risk decreased over time. By contrast, preceding AD had negligible effects on the risk for future MD. Familial risk was transmitted within disorders but there was little evidence of additional familial liability shared across disorders. CONCLUSIONS: Risk for developing AD was substantially increased by a prior episode of MD. The association was only partially accounted for by familial factors, providing support for a direct causal effect such as self-medication. The etiologic path from AD to MD was insignificant.

Adult↗

PubMed2006

Personality and major depression: a Swedish longitudinal, population-based twin study.

CONTEXT: Prior studies suggest that the personality traits of neuroticism and extroversion may be related to the liability to major depression (MD). OBJECTIVE: To clarify the magnitude and nature of the association between neuroticism and extroversion and the risk for MD. DESIGN: Longitudinal population-based twin cohort. SETTING: General community. PARTICIPANTS: A total of 20 692 members of same-sex twin pairs from the population-based Swedish Twin Registry who completed a self-report questionnaire assessing neuroticism and extroversion in 1972 and 1973 and were personally interviewed for lifetime history of MD more than 25 years later.Main Outcome Measure Lifetime history of modified DSM-IV MD. RESULTS: Levels of neuroticism strongly predicted the risks for both lifetime and new-onset MD. Twin modeling indicated that the association between neuroticism and MD resulted largely from shared genetic risk factors, with a genetic correlation of +0.46 to +0.47. Levels of extroversion were weakly and inversely related to the risks for lifetime and new-onset MD. This effect disappeared when we controlled for the level of neuroticism. Twin modeling produced similar results. CONCLUSIONS: Results from both longitudinal and genetic analyses support the hypothesis that neuroticism strongly reflects the liability to MD. This association arises largely because neuroticism indexes the genetic risk for depressive illness. However, substantial proportions of the genetic vulnerability to MD are not reflected in neuroticism. By contrast, extroversion is only weakly related to risk for MD.

Adult↗

PubMed2006

A Swedish national twin study of lifetime major depression.

OBJECTIVE: Substantial evidence supports the heritability of lifetime major depression. Less clear is whether genetic influences in major depression are more important in women than in men and whether genetic risk factors are the same in the two sexes. It is not known whether genetic effects on major depression are constant across historical cohorts. METHOD: Lifetime major depression was assessed at personal interview by modified DSM-IV criteria in 42,161 twins, including 15,493 complete pairs, from the national Swedish Twin Registry. Twin models were evaluated by using the program Mx. RESULTS: Model fitting indicated that the heritability of liability to major depression was significantly higher in women (42%) than men (29%) and the genetic risk factors for major depression were moderately correlated in men and women. No significant differences were seen in the etiologic roles of genetic and environmental factors in major depression in three cohorts spanning birth years 1900-1958. CONCLUSIONS: In the largest sample to date, lifetime major depression was moderately heritable, with estimates similar to those in prior studies. In accord with some but not other previous investigations, this study suggests both that the heritability of major depression is higher in women than in men and that some genetic risk factors for major depression are sex-specific in their effect. No evidence was found for differences in the roles of genetic and environmental risk factors in major depression in birth cohorts spanning nearly six decades.

Cohort Studies↗

PubMed2006

Toward a comprehensive developmental model for major depression in men.

OBJECTIVE: The multiple risk factors for major depression are interrelated through poorly understood developmental pathways. In 2002, the authors presented a developmental model for major depression in women. Based on similar methods, they here present an analogous model for men. METHOD: Using data from 2,935 adult male twins, interviewed twice over a 2-4-year period, the authors constructed, by means of structural equation modeling, an integrated etiologic model for major depression that predicts depressive episodes over 1 year from 18 risk factors conceptualized as five developmental "tiers" reflecting childhood, early adolescence, late adolescence, adulthood, and the last year. RESULTS: The best-fitting model, including six correlations and 76 paths, provided a good fit to the data, explaining 49% of the variance in the liability to depressive episodes. The overall results, similar to those seen in women, suggest that the development of major depression results from the action and interaction of three broad pathways of internalizing symptoms, externalizing symptoms, and adversity. Childhood parental loss and low self-esteem were more potent variables in the model in men than in women. Genetic risks for major depression had a broader spectrum of action in men than in women. The pathway to major depression through externalizing symptoms was not more prominent in men than in women. CONCLUSIONS: Major depression in men, as in women, is an etiologically complex disorder influenced by risk factors from multiple domains that act in developmental time. The similarities in etiologic pathways to major depression for men and women outweigh the modest differences.

Adolescent↗

PubMed2005

The differential impact of risk factors on illicit drug involvement in females.

BACKGROUND: Initiation of drug use and progression to abuse/dependence involve complex pathways. Potential risk factors may correlate with initiation or progression or both. Are there risk factors that associate with illicit drug use or illicit drug abuse/dependence? Is the magnitude of the association the same for use and abuse/dependence? Does this pattern of association differ across categories of drugs? METHODS: We used data from female-female adult twins to assess the association of 26 putative risk factors with use and abuse/dependence of six illicit psychoactive drugs. Drug involvement was represented by independent dichotomous outcomes and by a single ordinal variable. Odds ratios were obtained by logistic regression and a continuation ratio was used to test the magnitude of association. RESULTS: Factors associate in similar patterns with different drug categories. Some associated factors interact only with initiation while others relate with both stages. There is a stronger association of significant socio-demographic factors with drug use while the psychiatric diagnoses are more strongly associated with progression to abuse/dependence. CONCLUSIONS: Risk factors may be use-specific, abuse/dependence-specific or common to use and abuse/dependence. The trend of associations is similar across different illicit drugs. This suggests complex, interacting pathways that determine drug habits in individuals. These results are hypothesis-generating and future studies of causal relationships may draw from the outcomes presented in these analyses.

Adolescent↗

PubMed2005

Age at onset and familial risk for major depression in a Swedish national twin sample.

BACKGROUND: In many biomedical disorders, early age at onset (AAO) is an index of high liability to illness which is manifest by an increased risk of illness in relatives. Most but not all prior studies report such a pattern for major depression (MD). METHOD: Lifetime MD and AAO were assessed at personal interview using modified DSM-III-R criteria in 13864 twin pairs, including 4229 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models. RESULTS: Controlling for year of birth, gender, zygosity, co-twin history of MD and the interaction of zygosity and co-twin history, the best-fit model showed a significant main effect and a quadratic effect of AAO of MD in the co-twin on the log hazard ratio for MD in the index twin. When examined together, these effects predicted that from the ages of 15 to approximately 35 years, AAO of MD is moderately negatively related to risk of illness in relatives. However, past age 35, the function flattens out, with little change of risk in relatives with further increases of AAO. Even when the co-twin had a late AAO, the risk in the index twin substantially exceeded that seen when the co-twin had no history of MD. CONCLUSION: In this large sample, AAO is a meaningful, albeit modest, index of familial liability to MD. The relationship is nonlinear and results largely from an increased liability in individuals with an early AAO. These results should be interpreted in the context of the limitations of long-term recall.

Age of Onset↗

PubMed2005

Personality and comorbidity of common psychiatric disorders.

BACKGROUND: We know little about the degree to which comorbidity, socommonly seen among psychiatric disorders, arises from variation in normal personality. AIMS: To study the degree to which variation in normal personality accounts for the comorbidity of eight common psychiatric and substance use disorders. METHOD: Internalising disorders (major depression, generalised anxiety and panic disorders, phobias), externalising disorders (alcohol and drug dependence, antisocial personality and conduct disorders) and personality dimensions of neuroticism, extraversion and novelty seeking were assessed in 7588 participants from a population-based twin registry. The proportion of comorbidity explained by each personality dimension was calculated using structural equation modelling. RESULTS: Neuroticism accounted for the highest proportion of comorbidity within internalising disorders (20-45%) and between internalising and externalising disorders (19-88%). Variation in neuroticism and novelty seeking each accounted for a modest proportion (10-12% and 7-14%, respectively) of the comorbidity within externalising disorders. Extraversion contributed negligibly. CONCLUSIONS: High neuroticism appears to be a broad vulnerability factor for comorbid psychiatric disorders. Novelty seeking is modestly important for comorbid externalising disorders.

Adult↗

PubMed2005

The differential heritability of regular tobacco use based on method of administration.

Several large studies have demonstrated that the liability to smoke cigarettes is strongly genetically influenced. However, the role of genetic and environmental risk factors in the use of other common forms of tobacco use has yet to be studied. Data on the regular use of cigarettes, cigars, pipes, dip (moist snuff), and chewing tobacco from 2634 male twins were analyzed with ACE structural equation models. Twin similarity for regular cigarette and dip use was largely genetic in origin. However, twin resemblance for chewing tobacco was just about equally the result of genes and shared environment, and twin similarity for use of pipes and cigars was entirely the result of shared environmental factors. Thus, the genetic influences on the liability for regular tobacco use appear to vary based on tobacco type. The causes for the use of different forms of tobacco are complex and worthy of further study.

Adult↗

PubMed2004

Risks for conduct disorder symptoms associated with parental alcoholism in stepfather families versus intact families from a community sample.

BACKGROUND: It is not known if the prevalence of parental psychiatric disorders is higher in stepfather than intact families, or if parental alcoholism is differentially associated with risk for conduct disorder (CD) symptoms in stepfather families versus intact families. METHOD: The sample comprised 839 girls and 741 boys from 792 intact families and 99 girls and 67 boys from 83 stepfather families from a population-based registry of twins aged between 8 and 17 years. Children's current psychiatric symptoms were assessed at personal interview with the child, mother and father. Parental histories of psychiatric disorder were assessed at personal interview with each residential parent. Associations between CD symptoms and parental alcoholism were characterized using both linear and Poisson regression, and results are presented with and without adjustment for maternal drug use during pregnancy, parental conflict, and estimated socioeconomic status (SES) based on census tract data. RESULTS: Mothers from stepfather families had a higher lifetime prevalence of alcoholism, antisocial personality disorder, depression and social phobia than mothers from intact families. Stepfathers had a higher lifetime prevalence of alcoholism and depression than biological fathers from intact families. Children from stepfather families had more externalizing (CD/ODD) symptoms than children from intact families. Girls who lived with an alcoholic stepfather had significantly more CD symptoms than girls who lived with an alcoholic biological father. Boys who lived with an alcoholic stepfather had significantly fewer CD symptoms than boys who lived with an alcoholic biological father. This sex difference was statistically significant. Adjustment for maternal drug use during pregnancy, parental conflict, and estimated SES based on census tract data did not change these findings. CONCLUSIONS: Children living in stepfather families are exposed to more parental psychiatric risk factors than children from intact families. The increased risk for CD symptoms in girls (but not boys) from stepfather families is partly mediated by or associated with the stepfather's history of alcoholism.

Adolescent↗

PubMed2004

A population based twin study of sex differences in depressive symptoms.

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.

Adult↗

PubMed2003

Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed2003

Major depression and associated impairment: same or different genetic and environmental risk factors?

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.

Activities of Daily Living↗

PubMed2003

Dimensions of religiosity and their relationship to lifetime psychiatric and substance use disorders.

OBJECTIVE: 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. METHOD: 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). RESULTS: 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). CONCLUSIONS: 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.

Adult↗

PubMed2002

Toward a comprehensive developmental model for major depression in women.

OBJECTIVE: 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. METHOD: 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). RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed2002

Gender differences in the symptoms of major depression in opposite-sex dizygotic twin pairs.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗