Biomedical subjects

A C Heath

Publications and source records attributed to A C Heath.

At least 55 records · Page 3Linked to original sources

PubMed2000

A twin study of inattentive, aggressive, and anxious/depressed behaviors.

OBJECTIVE: To estimate genetic, environmental, and rater contrast influences on parental report of Attention Problems (AP), Aggressive (Agg), and Anxious/Depressed (AxD) behaviors of 492 twin pairs assessed with the Child Behavior Checklist. METHOD: A parent (92% mothers) of twins aged 8 to 12 years completed the Child Behavior Checklist. Genetic, shared and unique environmental, and rater bias effects were estimated for the AP, Agg, and AxD syndromes. Data on boys and girls were analyzed separately. Results were compared to prior research on related DSM disorders. RESULTS: Estimates of genetic influences on AP (60%-68%), Agg (70%-77%), and AxD (61%-65%) were high for both sexes, but lower for AP than prior findings using DSM attention-deficit hyperactivity disorder (ADHD). However, unlike equivalent analyses of DSM ADHD based on parental report, there was no evidence of rater bias. CONCLUSIONS: Estimates of genetic influence on these common child psychopathological domains were high. There was no evidence of rater contrast effects. These findings have implications for diagnosis, particularly when assessing families with multiple children.

Aggression↗

PubMed2000

A competitive enzyme-linked immunoassay using erythrocytes fixed to microtitre plates for anti-D quantitation in immunoglobulin products.

BACKGROUND AND OBJECTIVES: The batch control of anti-D immunoglobulin for prevention of haemolytic disease of the newborn necessitates assessment of its potency. Anti-D quantitation is usually performed using automated haemagglutination methodology although this can only be carried out in specialist centres. The aim of this study was to develop a simple and robust assay for anti-D quantitation. METHODS: We developed a competitive enzyme-linked immunoassay (EIA) in which unlabelled anti-D immunoglobulin and a biotinylated monoclonal anti-D compete for red cell binding. Binding of biotinylated anti-D is detected using an alkaline-phosphatase-labelled avidin preparation. The assay is conveniently carried out using erythrocytes fixed to microtitre plates. RESULTS: The competitive EIA was specific for anti-D activity, highly reproducible and showed good correlation with manufacturers' potency estimates using automated haemagglutination. The assay was quick and simple to perform using freshly prepared or stored plates, and the biotinylated monoclonal anti-D could be lyophilized in ampoules for distribution as a standardized reagent. CONCLUSIONS: The competitive EIA described can be used for the specific quantitation of anti-D and provides a robust alternative method to automated haemagglutination.

Antibodies, Monoclonal↗

PubMed2000

Transitions in drinking in adolescent females: evidence from the Missouri adolescent female twin study.

BACKGROUND: Data from adult community samples indicate that alcohol dependence originates in late adolescence, thus marking that period as a fruitful one for the study of transitions in drinking. METHODS: Using retrospective data about the timing of alcohol symptom onset from 1799 female twins who participated in the Missouri Adolescent Female Twin Study (MOAFTS), we integrated person-centered (PC) and variable-centered (VC) analyses to study 1-year transitions in alcohol symptomatology. A person-year data set reflecting the onset of 15 alcohol dependence symptoms was constructed, with each year in the young woman's life from the year of her first drink to her current age counting as one observation. Latent class analysis--a PC technique--identified classes of alcohol symptomatology for each person-year, and a lag function was used to identify class membership 1 year earlier. One-year transitions in drinking--a VC analysis--were then studied. RESULTS: Smoking, marijuana use, and conduct problems were consistent promoters of transitions to more severe drinking classes, but depressed affect was not a significant predictor. Parental history of alcohol problems or excessive drinking, particularly maternal history, was a significant predictor of more serious transitions to moderate and dependent problem drinking. CONCLUSIONS: These data confirm that even over a 1-year time frame there was considerable change in drinking patterns in this adolescent sample. Smoking was as potent a risk factor as conduct problems in promoting the progression of alcohol symptomatology, and the role of familial factors was found to be influential in transitions at the more severe end of the drinking spectrum.

Adolescent↗

PubMed2000

Heritability of self-reported health.

OBJECTIVE: To explore the contribution of genes and environmental factors to variation in a common measure (i.e., a five-point--excellent, very good, good, fair, and poor--Likert scale) of self-reported health. DATA SOURCES: Data were analyzed from 4,638 male-male twin pair members of the Vietnam Era Twin (VET) Registry who responded to a 1987 health survey. STUDY DESIGN: Varying models for the relationship between genetic and environmental influences on self-reported health were tested in an attempt to explain the relative contributions of additive genetic, shared and nonshared environmental effects, and health conditions reported since 1975 to perceived health status. DATA COLLECTION: A mail and telephone survey of health was administered in 1987 to VET Registry twins. PRINCIPAL FINDINGS: Variance component estimates under the best-fitting model included a 39.6 percent genetic contribution to self-reported health. In a model which included the effect of health condition, genes accounted for 32.5 percent and health condition accounted for 15.0 percent of the variance in self-reported health. The magnitude of the genetic contribution to perceived health status was not significantly different in a model with or without health condition. CONCLUSIONS: These data suggest over one-third of the variability of self-reported health can be attributed to genes. Since perceived health status is a major predictor of morbidity, mortality, and health services utilization, future analyses should consider the role of heritable influences on traditional health services variables.

Aged↗

PubMed2000

Smoking and the genetic contribution to alcohol-dependence risk.

Genes influence a person's risk of becoming a smoker as well as the risk of alcohol dependence. Because substantially higher rates of smoking are observed in alcoholics than in control groups, uncovering the mechanisms underlying this association may have important implications for both treatment and prevention. Data analyses from the 1981 Australian twin panel cohort confirm a positive genetic correlation between regular smoking and the risk of alcohol dependence that remains significant, even when sociodemographic and personality variables as well as histories of other psychopathologies are taken into account. Acute or chronic effects of smoking on subjective responses to alcohol may play a role in this association.

Alcoholism↗

PubMed1999

Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms.

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain.

Adult↗

PubMed1999

Major depressive disorder in a community-based twin sample: are there different genetic and environmental contributions for men and women?

BACKGROUND: Depression affects more women than men and often aggregates in families. Using a community-based sample of twins, we examined the contributions of genetic and environmental factors to the risk of developing major depressive disorder and the effect of sex and different definitions of depression on the relative contributions of genetic and environmental effects. Sex differences in genetic effects were also studied. METHODS: A volunteer sample of Australian twins (2662 pairs) was interviewed using an abbreviated version of the Semi-Structured Assessment for the Genetics of Alcoholism, a semi-structured lay interview designed to assess psychiatric disorders. Depression was defined using 3 different criteria sets: DSM-III-R major depressive disorder, DSM-IV major depressive disorder, and severe DSM-IV major depressive disorder. Genetic and environmental contributions to the liability to develop depression were estimated using genetic model fitting. RESULTS: Lifetime prevalences were 31% in women and 24% in men for DSM-III-R major depressive disorder, 22% in women and 16% in men for DSM-IV major depressive disorder, and 9% in women and 3% in men for severe DSM-IV major depressive disorder. In women, the simplest model to fit the data implicated genetic factors and environmental factors unique to the individual in the development of depression, with heritability estimates ranging from 36% to 44%. In men, depression was only modestly familial, and thus individual environmental factors played a larger role in the development of depression. For DSM-III-R major depressive disorder, there were statistically different estimates for heritability for men vs. women. For both sexes, the relative contributions of genetic and environmental factors were stable using different definitions of depression. CONCLUSIONS: There was moderate familial aggregation of depression in women and this primarily was attributable to genetic factors. In men, there was only modest familial aggregation of depression. For both men and women, individual environmental experiences played a large role in the development of depression. Major depressive disorder as defined by DSM-III-R was more heritable in women as compared with men. The relative contributions of genetic and environmental factors in the development of depression were similar for varying definitions of depression, from a broad definition to a narrow definition.

Adult↗

PubMed1999

Common genetic vulnerability for nicotine and alcohol dependence in men.

BACKGROUND: Nicotine and alcohol dependence often occur together. We examined data from male twin pairs to determine whether there are genetic or environmental influences common to nicotine and alcohol dependence, and, if so, to estimate the magnitude and correlation of these influences. METHODS: Subjects were 3356 male-male twin-pair members of the Vietnam Era Twin Registry who participated in a 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised. Genetic model fitting was performed to estimate the magnitude and correlation of genetic and environmental contributions to lifetime nicotine and alcohol dependence. RESULTS: The heritability of nicotine dependence was 60.3% (95% confidence interval [CI], 55.4%-65.2%); that of alcohol dependence, 55.1% (95% CI, 49.7%-60.5%). The best-fitting model for the co-occurrence of lifetime nicotine and alcohol dependence included a substantial genetic correlation between both disorders (r = 0.68; 95% CI, 0.61-0.74) and a modest unique environmental correlation (r = 0.23; 95% CI, 0.14-0.32). CONCLUSIONS: These data suggest a common genetic vulnerability to nicotine and alcohol dependence in men. This common genetic influence may partially explain the clinical and epidemiological observations that alcoholics are often dependent smokers.

Adult↗

PubMed1999

Brain event-related potentials, dopamine D2 receptor gene polymorphism, and smoking.

This paper explores the relationship between the DRD2 gene polymorphism, P300, and smoking. Both smoking and DRD2 have significant reducing effects on P300 amplitude. The effect of smoking is apparent only in the presence of the A1 allele of the DRD2 locus. Transmission/disequilibrium analyses show a negative association between the A2 allele and smoking initiation, suggesting a protective effect of this allele. When the sample is stratified into lower- and higher-P300 categories, we find a significant association between A1 and current smoking only in individuals with lower P300. Both concordance for smoking and DRD2 genotype are significant predictors of sib-pair similarity in P300 amplitude. These results suggest a synergistic effect of different neurogenetic risk factors contributing to nicotine dependence. Neurocognitive variation (P300) may moderate the association between DRD2 and smoking. Alternatively, DRD2 genotype may modulate the long-term impact of nicotine on neurocognitive functioning.

Age Factors↗

PubMed1999

Somatic distress as a distinct psychological dimension.

BACKGROUND: Somatoform disorders such as neurasthenia and chronic fatigue are characterized by a combination of prolonged fatigue and disabling neuropsychological and neuromuscular symptoms. However, the debate concerning the theoretical underpinnings of somatic disorders resembles the perennial dispute over the taxonomy of anxiety and depression. The objective of this study is to analyse the dimensional structure of items measuring anxiety, depression, phobic anxiety, somatic distress, and insomnia. It is anticipated that somatic distress should emerge as empirically distinct from measures of anxiety and depression, thereby lending support to proponents of the construct as independent of both anxiety and depression symptomatology. METHODS: A 33-item self-report symptom inventory derived from the SCL-90 and DSSI/sAD scales was used to measure recently experienced psychiatric distress in the form of depression, anxiety, phobic anxiety, somatic distress, and insomnia. SCL and DSSI/sAD items were measured on a four-point distress scale from 1 'not-at-all' to 4 'unbearably'. The inventory was administered to a community-based sample of 3468 Australian twins between the ages of 18 and 28. RESULTS: Factor analysis using Polychoric correlations and a Promax rotation criterion produced four factors: depression, phobic anxiety, somatic distress, and sleep disturbance. CONCLUSION: Results from the current factor analysis, together with the documented prevalence of somatic disorders, including evidence regarding the genetic and biological independence of somatic symptomatology, lend support to the argument that somatic symptoms, although correlated, are independent of anxiety and depression.

Adult↗

PubMed1999

Genetic influences on post-natal depressive symptoms: findings from an Australian twin sample.

BACKGROUND: Conflicting evidence exists on causes of vulnerability to post-natal depression. We investigated genetic and environmental influences on variation in post-natal depressive symptoms (PNDS) following first live birth, and sources of covariation with the personality trait Neuroticism and lifetime major depression occurring post-natally (DEP-PN) and at other times (DEP-XPN) to test for shared genetic influences. METHOD: Retrospective interview and questionnaire data from 838 parous female twin pairs (539 monozygotic, 299 dizygotic) from the Australian National Health and Medical Research Council volunteer adult twin register were used for multivariate genetic model-fitting. Data on PNDS were evaluated for consistency with diagnostic interview assessment. RESULTS: Genetic factors explained 38% of variance in PNDS (95% confidence interval 26-49%) and 25% of the variance in interview-assessed DEP-PN. The genetic correlation between PNDS and lifetime major depression (DEP-PN and DEP-XPN) was low (r(g) = 0.17, 95% confidence interval = 0.09-0.28), suggesting that the questionnaire was measuring a construct other than postnatally occurring major depression, possibly post-natal dysphoria. Associations between PNDS and obstetric factors were very modest. CONCLUSIONS: Findings suggest modest genetic influences on major depression occurring postnatally. Independent and stronger genetic influences identified for post-natal symptomatology or dysphoria (PNDS) justify further investigation.

Adult↗

PubMed1999

The structure of genetic and environmental risk factors for three measures of disordered eating.

BACKGROUND: The study explored the genetic and environmental risk factors for both the behaviours and attitudes characteristic of disordered eating. METHODS: In three waves of data collection, information was collected from female twins regarding their eating and attitudes towards eating, weight and shape. The first assessment consisted of a self-report questionnaire (1988-9) with 1682 women. The second assessment consisted of a semi-structured psychiatric interview schedule (1992-3), completed by 1852 women, many of whom had completed Wave 1 assessment. The third assessment, with 325 women chosen from Waves 1 and 2 (1995-6), consisted of a semi-structured interview (the Eating Disorder Examination). RESULTS: As only one twin pair was concordant for lifetime bulimia nervosa at Wave 3 assessment, ordinal measures of all assessments were used in a multivariate genetic analysis. Results indicated that additive genetic and non-shared environmental influences best explained variance in liability to disordered eating, with about 60% (95% CI 50-68) of the variance explained by genetic factors. Comparison with a model allowing for the effects of shared environment indicated genetic factors accounted for a similar degree of variance (59%, 95% CI 36-68). CONCLUSION: Liability to the development of the behaviours and attitudes characteristic of eating disorders is best explained by both environmental and genetic factors, with covariation between the three measures best explained by a single latent phenotype of disordered eating which has a heritability of 60%.

Adult↗

PubMed1999

Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk.

BACKGROUND: Substantial evidence exists for an important genetic contribution to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs. METHODS: Telephone interview follow-up data were obtained on twins from male, female and unlike-sex twin pairs who had participated in an alcohol challenge study in 1979-81, as well as other pairs from the same Australian twin panel surveyed by mail in 1980-82. RESULTS: At follow-up, alcohol challenge men did not differ from other male twins from the same age cohort on measures of lifetime psychopathology or drinking habits; but alcohol challenge omen were on average heavier drinkers than other women. A composite alcohol sensitivity measure, combining subjective intoxication and increase in body-sway after alcohol challenge in 1979-81, exhibited high heritability (60 %). Parental alcoholism history was weakly associated with decreased alcohol sensitivity in women, but not after adjustment for baseline drinking history, or in men. High alcohol sensitivity in men was associated with substantially reduced alcohol dependence risk (OR = 0.05, 95% CI 0.01-0.39). Furthermore, significantly decreased (i.e. low) alcohol sensitivity was observed in non-alcoholic males whose MZ co-twin had a history of alcohol dependence, compared to other non-alcoholics. These associations remained significant in conservative analyses that controlled for respondents' alcohol consumption levels and alcohol problems in 1979-81. CONCLUSIONS: Men (but not women) at increased genetic risk of alcohol dependence (assessed by MZ co-twin's history of alcohol dependence) exhibited reduced alcohol sensitivity. Associations with parental alcoholism were inconsistent.

Adult↗

PubMed1999

Phenotypic and genetic factors in motives for smoking.

Underlying phenotypic and genetic factors involving motives for smoking were assessed using data from 1756 twins, including 390 complete pairs. Respondents were aged 50 or older and included both current and former smokers. The Motives for Smoking Questionnaire (MSQ) hypothesizes eight correlated but distinct motives for smoking, which correspond to pharmacological and nonpharmacological second-order factors. This paper concentrates on the pharmacological motives. Principal-factor analysis recovered five categories. Items constituting Sedative, Stimulative, and Addictive reasons for smoking merged into one factor, whereas Automatic smoking, also considered to have pharmacological origins, formed a separate factor. Twin analysis was used to test for genetic effects and to determine whether these factors, although combined phenotypically, were affected by distinct genetic or environmental influences. Genetic effects accounted for a significant amount of the variance in the four hypothesized pharmacological motives for smoking, as did shared environment. The separate factor for Automatic smoking in the phenotypic analysis was due to environmental effects, and shared environment was a greater influence on Automatic smoking for women than men. One common effect explained the genetic variance; no genetic influence uniquely affected any specific motive. Therefore, individual differences in the hypothesized pharmacological motives for smoking appear to originate from a common genetic pathway.

Aged↗

PubMed1999

The genetics of smoking initiation and quantity smoked in Dutch adolescent and young adult twins.

Not much is known about the genetic and environmental determinants of various aspects of substance use in adolescents. This study examined whether the inheritance of initiation of tobacco use in adolescents is independent of the inheritance of the number of cigarettes smoked. Alternative multifactorial threshold models were applied to data on tobacco use in 1676 Dutch adolescent twin pairs. The three models that were considered are (i) the single liability dimension model, (ii) the independent liability dimension model, and (iii) the combined model (CM). The results showed that there is not one underlying continuum of liability to smoking. The CM was the best-fitting model. This model postulates that there are separate initiation and quantity dimensions but allows for the possibility that there are some individuals who are so low on the liability to level of consumption that they are not using tobacco. There were no differences between males and females in the magnitude of the genetic and environmental influences on individual differences in smoking initiation and quantity smoked. Smoking initiation was influenced by genetic factors (39%) and shared environmental influences (54%). Once smoking is initiated genetic factors determine to a large extent (86%) the quantity that is smoked.

Adolescent↗

PubMed1999

A twin study of drinking and smoking onset and latencies from first use to regular use.

The early onset of alcohol and tobacco use has been associated with increased risk for later substance abuse and dependence problems. This study investigated genetic and environmental influences on age at onset of alcohol and tobacco use by examining twin resemblance for several retrospectively reported onset milestones including age at first use, age at first alcohol intoxication experience, and age at regular use. In addition, we also examined the latency between age at first use and age at regular use of tobacco and alcohol. The subjects were a volunteer sample of older adult twins 50 to 96 years of age. MZ twin correlations for age at first alcohol use and age at first tobacco use were .57 and .44, respectively, compared to .45 and .37 for DZ same-sex twins. MZ twins correlated .30 and .26 for the latencies between first use and regular use of alcohol and of tobacco, while DZ correlations were -.01 and .05, respectively. Biometrical model-fitting results confirmed that familial resemblance for age at first use for both alcohol and tobacco was largely the result of shared environmental factors, while the latencies between first use and regular patterns of use were more genetically influenced. These findings add to a growing body of literature suggesting that initiation of substance use is influenced primarily by environmental rather than genetic factors.

Adolescent↗

PubMed1999

A note on issues in meta-analysis for behavioral genetic studies using categorical phenotypes.

Meta-analysis of behavioral genetic studies would provide (i) tighter confidence intervals around parameter estimates, (ii) clarification of apparently discrepant study findings, and (iii) a mechanism for analyzing systematic causes of between-study differences. We examined some key issues that arise in the meta-analysis of categorical phenotypes. Data were simulated under a multifactorial threshold model that assumed an underlying normal liability distribution, and summary statistics (probandwise concordance rate, recurrence risk ratio, odds ratio, kappa) compared for given values of the liability correlation between relatives and given population prevalence. Although the odds ratio and kappa statistic performed well at moderate to high values of the population prevalence (15-50%), at low values all of these statistics were sensitive to overall prevalence. In cases where the assumption of a multifactorial threshold model is reasonable, direct estimation of genetic and environmental parameters from the summary statistics from all studies appears to be a preferable strategy. For cases where data from non-randomly ascertained samples are used, the impact of misspecification of the model for ascertainment was examined. For some parameter values, such misspecifications led to quite serious biases to estimates of genetic and environmental parameters. These biases varied in complex ways as a function of research design and of the true causes of variation in the population, so that the same misspecification could lead to an overestimate of the importance of genetic influences in twin data but an underestimation in adoption data or to an overestimate of the importance of genetic effects from twin data if shared environmental as well as genetic influences were simulated but an underestimate of genetic effects if shared environmental effects were assumed unimportant. These complexities emphasize the importance of being sensitive to the effects of misspecifying ascertainment corrections in any meta-analysis of behavioral genetic data.

Confidence Intervals↗

PubMed1999

Genetic and social determinants of initiation and age at onset of smoking in Australian twins.

Retrospective data on age at onset of smoking, reported by 3810 adult Australian twin pairs, were analyzed to determine the role of genetic and environmental factors in the onset of smoking. Results of nonmetric multidimensional scaling supported a two-process model in which different etiologic factors determined which individuals were at risk of becoming smokers and the age at onset of smoking in those who were at risk. Parametric model-fitting confirmed this difference. For female twins and younger male twins (aged 30 years or less), the onset of smoking was strongly influenced by genetic factors, with shared and nonshared environmental effects having a more modest impact. For older male twins, shared environmental influences on onset of smoking were very important, and the influence of genetic predisposition was slight. The age at which smoking onset occurred, however, was influenced by both genetic and nonshared environmental effects, but not by shared environmental effects, in both sexes and both cohorts.

Adolescent↗