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Kenneth S Kendler

Publications and source records attributed to Kenneth S Kendler.

At least 91 records · Page 5Linked to original sources
PubMed2004

Sources of individual differences in stressful life event exposure in male and female twins.

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.

Adult↗
PubMed2004

A twin study of personality and illicit drug use and abuse/dependence.

Although personality measures such as neuroticism (N), extraversion (E) and novelty-seeking (NS) are associated with the use and abuse/dependence of illicit drugs, little is known about the degree to which these associations are due to genetic or environmental factors. The goal of this analysis was to estimate the extent of genetic and environmental overlap between three dimensions of personality (N, E and NS) and illicit psychoactive substance use and abuse/dependence. Using data from adult male and female twins from the Mid-Atlantic Twin Registry, we used the structural equation modeling package Mx to perform bivariate Cholesky decompositions for personality measures of N, E and NS, individually with cannabis, cocaine, sedatives, stimulants and hallucinogens. This was done separately for use and for a polychotomous diagnosis of abuse and/or dependence. Sex differences were tested. The phenotypic relationship between personality and use and abuse/dependence of illicit drugs were moderate and most of the covariance was explained by genetic factors. Sexes could be equated for N and E but not for NS. For NS, use and abuse/dependence of illicit drugs showed greater phenotypic and genetic overlap in males than females. Of the personality measures, NS and illicit drug use and abuse/dependence were most closely related. NS was most closely related to cannabis use while N showed significant genetic overlap with sedative use. NS in males appears to be a good indicator of risk for cannabis use. This result may be useful for candidate gene studies.

Adult↗
PubMed2003

Multipoint and single point non-parametric linkage analysis with imperfect data.

We used simulation to explore the impact of common data imperfections (i.e., missing parents, genotyping error, map error, and missing genotypes) upon the performance of multipoint and single point linkage analysis in the analyses of linkage data from pairs of siblings affected with an idealized complex trait. The performance of single point and multipoint linkage was similar under an unrealistic best case scenario; however, when four data imperfections were combined, the performance of single point linkage analysis appeared to be superior to multipoint. The absence of parental genotypes in the presence of 1% genotype error led to marked degradation of linkage signal, particularly for multipoint analyses.

Computer Simulation↗
PubMed2003

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia.

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

Bipolar Disorder↗
PubMed2003

Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies.

CONTEXT: There are many published twin studies of schizophrenia. Although these studies have been reviewed previously, to our knowledge, no review has provided quantitative summary estimates of the impact of genes and environment on liability to schizophrenia that also accounted for the different ascertainment strategies used. OBJECTIVE: To calculate meta-analytic estimates of heritability in liability and shared and individual-specific environmental effects from the pooled twin data. DATA SOURCES: We used a structured literature search to identify all published twin studies of schizophrenia, including MEDLINE, dissertation, and books-in-print searches. STUDY SELECTION: Of the 14 identified studies, 12 met the minimal inclusion criteria of systematic ascertainment. DATA SYNTHESIS: By using a multigroup twin model, we found evidence for substantial additive genetic effects-the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia-joint estimate, 11% (95% confidence interval, 3%-19%). CONCLUSIONS: Despite evidence of heterogeneity across studies, these meta-analytic results from 12 published twin studies of schizophrenia are consistent with a view of schizophrenia as a complex trait that results from genetic and environmental etiological influences. These results are broadly informative in that they provide no information about the specific identity of these etiological influences, but they do provide a component of a unifying empirical basis supporting the rationality of searches for underlying genetic and common environmental etiological factors.

Diseases in Twins↗
PubMed2003

A twin study of the genetics of fear conditioning.

BACKGROUND: Fear conditioning is a traditional model for the acquisition of fears and phobias. Studies of the genetic architecture of fear conditioning may inform gene-finding strategies for anxiety disorders. The objective of this study was to determine the genetic and environmental sources of individual differences in fear conditioning by means of a twin sample. METHODS: Classic fear conditioning data were experimentally obtained from 173 same-sex twin pairs (90 monozygotic and 83 dizygotic). Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure was the electrodermal skin conductance response. We applied structural equation modeling methods to the 3 conditioning phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors underlie individual variation in associative and nonassociative learning. RESULTS: All components of the fear conditioning process in humans demonstrated moderate heritability, in the range of 35% to 45%. Best-fitting multivariate models suggest that 2 sets of genes may underlie the trait of fear conditioning: one that most strongly affects nonassociative processes of habituation that also is shared with acquisition and extinction, and a second that appears related to associative fear conditioning processes. In addition, these data provide tentative evidence of differences in heritability based on the fear relevance of the stimuli. CONCLUSION: Genes represent a significant source of individual variation in the habituation, acquisition, and extinction of fears, and genetic effects specific to fear conditioning are involved.

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

The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women.

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

Adult↗
PubMed2003

Genetic and environmental contributions to obesity and binge eating.

OBJECTIVE: Binge eating is present in a substantial proportion of obese individuals. A tendency toward obesity has been identified as a risk factor for eating disorders such as bulimia nervosa and binge eating disorder. The purpose of this article was to determine the extent of overlap between genetic and environmental factors that contribute to the liability to obesity and binge eating. RESEARCH METHOD: In a population-based sample of 2163 female twins, we conducted bivariate twin modeling to explore the relation between the genetic and environmental risk factors for obesity and binge eating. RESULTS: Bivariate twin modeling revealed substantial heritability for obesity (0.86: 95% CI, 0.77-0.94), moderate heritability for binge eating (0.49: 95% CI, 0.38-0.61), and a modest genetic correlation of +.34 (95% CI, 0.19-0.50) between the two traits. CONCLUSIONS: Both binge eating and obesity are heritable conditions, and there seems to be only modest overlap in the genetic risk factors that increase liability to each condition.

Adolescent↗
PubMed2003

Of genes and twins.

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Diseases in Twins↗
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

Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia.

OBJECTIVE: Childhood onset of "adult" psychiatric disorders may be caused, in part, by more salient genetic risk. In this study, the rates of schizophrenia spectrum disorders among parents of patients with childhood-onset and adult-onset schizophrenia and parents of community comparison subjects were compared. METHOD: To assess the presence of axis I and axis II disorders associated with schizophrenia, parents of patients with childhood-onset schizophrenia (95 parents), patients with adult-onset schizophrenia (86 parents), and community comparison subjects (123 parents) were interviewed directly by using semistructured instruments. Information on 19 additional parents (parents of childhood-onset patients, N=2; parents of adult-onset patients, N=11; parents of community comparison subjects, N=6) was obtained by using a family history interview with the same instruments. Transcribed interviews were scored by a rater blind to group membership, and the morbid risks for schizophrenia spectrum disorders in the three groups were compared. RESULTS: Parents of patients with childhood-onset schizophrenia had a significantly higher morbid risk of schizophrenia spectrum disorders (24.74%) than parents of patients with adult-onset schizophrenia (11.35%), and parents of both patient groups had a greater risk of schizophrenia spectrum disorders than did parents of comparison subjects (1.55%). CONCLUSIONS: Parents of patients with childhood-onset schizophrenia have a higher rate of schizophrenia spectrum disorders than parents of patients with adult-onset illness. This is consistent with the hypothesis that a childhood onset of schizophrenia is due, at least in part, to a greater familial diathesis for the disorder.

Adult↗
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↗
PubMed2003

Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins.

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

Adult↗
PubMed2002

Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia.

Prior evidence has supported the existence of multiple susceptibility genes for schizophrenia. Multipoint linkage analysis of the 270 Irish high-density pedigrees that we have studied, as well as results from several other samples, suggest that at least one such gene is located in region 6p24-21. In the present study, family-based association analysis of 36 simple sequence-length-polymorphism markers and of 17 SNP markers implicated two regions, separated by approximately 7 Mb. The first region, and the focus of this report, is 6p22.3. In this region, single-nucleotide polymorphisms within the 140-kb gene DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strongly associated with schizophrenia. Uncorrected, empirical P values produced by the program TRANSMIT were significant (P<.01) for a number of individual SNP markers, and most remained significant when the data were restricted to include only one affected offspring per nuclear family per extended pedigree; multiple three-marker haplotypes were highly significant (P=.008-.0001) under the restricted conditions. The pattern of linkage disequilibrium is consistent with the presence of more than one susceptibility allele, but this important issue is unresolved. The number of markers tested in the adjacent genes, all of which are negative, is not sufficient to rule out the possibility that the dysbindin gene is not the actual susceptibility gene, but this possibility appears to be very unlikely. We conclude that further investigation of dysbindin is warranted.

Animals↗
PubMed2002

The borderline diagnosis III: identifying endophenotypes for genetic studies.

Although it is generally acknowledged that borderline personality disorder (BPD) has a complex, multifactorial etiology with interacting genetic and environmental substrates, the specific genetic underpinnings of this disorder have not been extensively investigated. Family aggregation studies suggest the heritability for BPD as a diagnosis, but the genetic basis for this disorder may be stronger for dimensions such as impulsivity/aggression and affective instability than for the diagnostic criteria itself. Family, adoptive, and twin studies also converge to support an underlying genetic component to the disorder. An endophenotypic approach to defining the genetics of this complex disorder may be called for. Twin studies in an epidemiologic, non-clinically ascertained sample using both diagnostic measures and laboratory measures that can be operationalized, including neuropsychologic, psychophysiologic, and operationalized behavioral tests, may be useful. Large-scale family studies of clinically ascertained samples with careful diagnostic demarcation and measurement of endophenotypes in probands and relatives may also prove to be a promising approach. The use of laboratory paradigms for measures of aggression and affective instability are discussed in the context of such endophenotypic approaches.

Borderline Personality Disorder↗
PubMed2002

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample.

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Africa↗