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Kenneth S Kendler

Publications and source records attributed to Kenneth S Kendler.

At least 73 records · Page 4Linked to original sources
PubMed2004

Regulator of G-protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families.

The regulator of the G-protein signaling 4 (RGS4) gene was shown to have a different expression pattern in schizophrenia patients in a microarray study. A family-based study subsequently implicated the association of this gene with schizophrenia. We replicated the study with our sample from the Irish Study of High Density Schizophrenia Families (ISHDSF). Single marker transmission disequilibrium tests (TDT) for the four core SNPs showed modest association for SNP 18 (using a narrow diagnostic approach with FBAT P = 0.044; with PDT P = 0.0073) and a trend for SNP 4 (with FBAT P = 0.1098; with PDT P = 0.0249). For SNP 1 and 7, alleles overtransmitted to affected subjects were the same as previously reported. Haplotype analyses suggested that haplotype G-G-G for SNP1-4-18, which is the most abundant haplotype (42.3%) in the Irish families, was associated with the disease (narrow diagnosis, FBAT P = 0.0061, PDT P = 0.0498). This was the same haplotype implicated in the original study. While P values were not corrected for multiple testing because of the clear prior hypothesis, these results could be interpreted as supporting evidence for the association between RGS4 and schizophrenia.

Alleles↗
PubMed2004

Candidate genes for nicotine dependence via linkage, epistasis, and bioinformatics.

Many smoking-related phenotypes are substantially heritable. One genome scan of nicotine dependence (ND) has been published and several others are in progress and should be completed in the next 5 years. The goal of this hypothesis-generating study was two-fold. First, we present further analyses of our genome scan data for ND published by Straub et al. [1999: Mol Psychiatry 4:129-144] (PMID: 10208445). Second, we used the method described by Cox et al. [1999: Nat Genet 21:213-215] (PMID: 9988276) to search for epistatic loci across the markers used in the genome scan. The overall results of the genome scan nearly reached the rigorous Lander and Kruglyak [1995: Nat Genet 11:241-247] criteria for "significant" linkage with the best findings on chromosomes 10 and 2. We then looked for correspondence between genes located in the 10 regions implicated in affected sibling pair (ASP) and epistatic linkage analyses with a list of genes suggested by microarray studies of experimental nicotine exposure and candidate genes from the literature. We found correspondence between linkage and microarray/candidate gene studies for genes involved with the mitogen-activated protein kinase (MAPK) signaling system, nuclear factor kappa B (NFKB) complex, neuropeptide Y (NPY) neurotransmission, a nicotinic receptor subunit (CHRNA2), the vesicular monoamine transporter (SLC18A2), genes in pathways implicated in human anxiety (HTR7, TDO2, and the endozepine-related protein precursor, DKFZP434A2417), and the micro 1-opioid receptor (OPRM1). Although the hypotheses resulting from these linkage and bioinformatic analyses are plausible and intriguing, their ultimate worth depends on replication in additional linkage samples and in future experimental studies.

Chromosome Mapping↗
PubMed2004

Summer birth and deficit schizophrenia: a pooled analysis from 6 countries.

BACKGROUND: In some reports, summer birth has been associated with deficit schizophrenia. Deficit schizophrenia and nondeficit schizophrenia also differ in several other ways. OBJECTIVE: To conduct a combined analysis of the published and unpublished data sets from the northern hemisphere that relate deficit and nondeficit schizophrenia to month of birth. DATA SOURCES: Studies of season of birth in which it was possible to make a deficit/nondeficit categorization. STUDY SELECTION: Published studies with samples of convenience and all known population-based studies with the deficit/nondeficit categorization were included. The studies came from 6 countries. DATA EXTRACTION: Three published studies of samples of convenience, 2 population-based prevalence studies, and 5 population-based studies that approximated incident samples were included. Month of birth was compared for deficit and nondeficit schizophrenia, using meta-analytic fixed-effects models. DATA SYNTHESIS: A group x month goodness-of-fit chi2 showed a significant difference between deficit and nondeficit subjects in season of birth (P < .001) in the studies that approximated incidence. This difference was largely due to an increase in deficit schizophrenia births in June and July (odds ratio, 1.9; 95% confidence interval, 1.3-2.9). Similar results were found in the prevalence studies. A similar pattern was found in 2 of the 3 samples of convenience, but when combined, these 3 samples did not show a significant deficit/nondeficit difference. CONCLUSIONS: Deficit schizophrenia has a season of birth pattern that differs from that of nondeficit schizophrenia. This analysis supports the notion of a separate disease within schizophrenia.

Cohort Studies↗
PubMed2004

Sex influences on shared risk factors for bulimia nervosa and other psychiatric disorders.

BACKGROUND: 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. OBJECTIVE: To determine whether sex influences shared risk factors between bulimia nervosa (BN) and other forms of psychopathology. DESIGN: The study examines associations between BN and other forms of psychopathology in twin pairs using interview and survey reports. SETTING: Twins from the Virginia population-based twin registry. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗
PubMed2004

Undue influence of weight on self-evaluation: a population-based twin study of gender differences.

OBJECTIVE: To explore the extent to which genetic and environmental factors contribute to liability to placing undue importance on weight as an indicator of self-evaluation and to determine whether differences exist across genders in the nature and magnitude of these effects. METHOD: Self-report data were collected on 8,045 same-sex and opposite-sex twins, aged 18-31 years, from a population-based registry of Norwegian twins. Structural equation modeling was utilized to estimate the relative contribution of genetic and environmental factors to liability for undue influence of weight on self-evaluation, allowing for gender-specific effects. RESULTS: Individual variation in undue influence of weight on self-evaluation was best explained by shared and individual environmental influences. No significant gender differences were found. Shared environmental factors accounted for 31% of the variance. DISCUSSION: These results raise the possibility that there may be distinct sources of familial resemblance for different symptoms of bulimia nervosa as codified in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994).

Adolescent↗
PubMed2004

The genetic relationship of personality to major depression and schizophrenia.

Since ancient times, dimensions of personality have been linked with the liability to psychiatric illness. In modern times, several research approaches suggest that personality and the liability to psychiatric illness such as schizophrenia and major depression (MD) are influenced by many of the same genes. If this is true, it could shed light on the genetic architecture of psychiatric illness. It could also validate the use of personality measures in unaffected relatives in linkage and association studies of psychiatric illness. This approach could potentially increase statistical power to detect genetic effects. The personality trait neuroticism (N) may be genetically related to MD, while schizotypal traits may be genetically related to schizophrenia. Twin studies have reported that most of the covariation between N and MD is due to shared additive genetic factors. Adoption studies have demonstrated that the biological offspring of schizophrenic mothers are more likely to have schizotypal personality disorder than are children of control mothers. At the current time, only one genome wide scan of N has been published, which does show some overlap in linkage results with genome scans of MD. However, this should be replicated and more rigorously studied. At the present time, there are no established susceptibility genes for MD. When these are established, it will be necessary to assess their relationship with N. Currently, no genome scans of schizotypy have been published. Furthermore, although several putative susceptibility genes for schizophrenia have been reported and replicated, only one--catechol-O-methyltransferase (COMT)--has been tested in schizotypy.

Major Depressive Disorder↗
PubMed2004

A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence.

BACKGROUND: Numerous twin studies have reported significant genetic contributions to the variability of tobacco initiation (TI), while fewer studies have shown similar results for the persistence of smoking behavior, or nicotine dependence (ND). As the development of ND requires regular tobacco use (RTU) which in turn requires TI, a conditional approach is necessary. METHOD: We used structural equation modeling of multi-step conditional processes to examine the relationship between genetic and environmental risk factors for TI, RTU and ND. The tobacco variables were assessed by personal interview in female, male and opposite-sex twin pairs from the population-based Virginia Twin Registry. RESULTS: The results suggested that the liabilities to TI, RTU and ND were correlated. Over 80 % of the variance in liability to TI and RTU were shared, and a smaller proportion was shared between RTU and ND. The heritabilities were estimated at 75 %, 80 % and 60 % respectively for TI, RTU and ND. The variance specific to liability to RTU was entirely accounted for by additive genetic factors. Only a modest part of the heritability in liability of ND was due to genetic factors specific to ND. Shared environmental factors were not significant. No sex differences were found for the sources of variation or causal paths, but prevalences were significantly greater in males versus females. CONCLUSIONS: This study showed significant overlap in the contribution of genetic factors to individual differences in TI, RTU and ND. Furthermore, there was evidence for significant additional genetic factors specific to RTU and ND.

Adult↗
PubMed2004

Level of family dysfunction and genetic influences on smoking in women.

BACKGROUND: An adoption study of alcoholism suggests that in women, the impact of genetic risk factors become greater in the presence of conflict in the family of origin. Is the same true for cigarette smoking (CS)? METHOD: We obtained, in a sample of 1676 twins from female female twin pairs from a population-based register, a measure of maximum lifetime CS (divided into six ordinal categories) and family dysfunction (FD) assessed as the mean report of up to four informants (twin, co-twin, mother, father). Statistical analysis was conducted by traditional regression analysis and a moderator structural equation twin model using the computer program Mx. RESULTS: With increasing levels of FD, maximum CS increased substantially while correlations for CS in monozygotic (MZ) and dizygotic (DZ) twins decreased modestly. Regression analyses demonstrated reduced twin-pair resemblance for CS with increasing levels of FD. The best-fit structural equation model found high levels of heritability for CS and no evidence for a role of shared environment. With increasing levels of FD, the proportion of variance in CS due to genetic factors (i.e. heritability) decreased while that due to unique environmental effects increased. CONCLUSIONS: Several different statistical methods suggested that, contrary to prediction, heritability of CS decreased rather than increased with higher levels of dysfunction in the family of origin. The hypothesis that genetic effects for psychiatric and drug-use disorders become stronger in more adverse environments is not universally true.

Adult↗
PubMed2004

A twin study of early cannabis use and subsequent use and abuse/dependence of other illicit drugs.

INTRODUCTION: Cannabis use is strongly associated with the use and abuse/dependence of other illicit drugs. Gateway and common liabilities models have been employed to explain this relationship. We sought to examine this association using a combination of the discordant twin design and modeling methods. METHOD: We assess the relationship between early cannabis use and the subsequent use and abuse/ dependence of other illicit drugs in a population-based sample of male and female twin pairs using four analyses: (i) analysis of the association between early cannabis use and other illicit drug use and abuse/dependence in the entire sample of twins, (ii) assessment of the influence of early cannabis use in twin 1 on twin 2's use or abuse/dependence of other illicit drugs, (iii) use of twin pairs discordant for early cannabis use in a discordant twin design and (iv) a model-fitting procedure. RESULTS: We found: (i) a strong association between early cannabis use and use and abuse/dependence of other illicit drugs in the sample, (ii) twin 1's early cannabis use is significantly associated with the twin 2's other illicit drug use, (iii) the role of correlated genetic factors with some evidence for a causal influence, and (iv) the correlated liabilities model fits the data well. CONCLUSIONS: Early cannabis use is strongly associated with other illicit drug use and abuse/dependence. The relationship arises largely due to correlated genetic and environmental influences with persisting evidence for some causal influences.

Adult↗
PubMed2004

Childhood sexual abuse, stressful life events and risk for major depression in women.

BACKGROUND: In animals, early trauma can produce long-lasting changes in sensitivity to the pathogenic effects of stress. To explore whether similar processes occur in humans, we examine whether childhood sexual abuse (CSA) in women alters sensitivity in adulthood to the depressogenic effects of stressful life events (SLEs). METHOD: A history of CSA was obtained from a population-based sample of 1404 female adult twins. Cox Proportional hazard models were used to predict onsets of episodes of DSM-III-R major depression (MD) in the past year from previously assessed levels of neuroticism (N), CSA and past-year SLEs scored on long-term contextual threat. RESULTS: In the best-fit model, onset of MD was predicted by CSA, SLEs and N. Individuals with CSA (and especially with severe CSA) had both an overall increased risk for MD and a substantially increased sensitivity to the depressogenic effects of SLEs. A 'dose-response' relationship between severity of CSA and sensitivity to SLEs was clearer in those with low to average levels of N than in those with high levels of N. CONCLUSION: As documented with physiological responses to a standardized laboratory stressor, CSA increases stress sensitivity in women in a more naturalistic setting. Both genetic and early environmental risk factors can produce long-term increase in the sensitivity of individuals to depressogenic life experiences.

Adolescent↗
PubMed2004

Cannabis and other illicit drugs: comorbid use and abuse/dependence in males and females.

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.

Cannabinoids↗
PubMed2004

Characteristics of men with persistent thinness.

OBJECTIVE: Although Western society is increasingly obesogenic, some individuals maintain low weights. Thin women manifest fewer eating disorders and higher self-esteem. However, little is known about persistently thin men. RESEARCH METHODS AND PROCEDURES: Participants completed measures of demographics, psychiatric history, body size, eating behavior, and personality. RESULTS: Thinness was associated with less eating pathology. Thin men were more likely to meet criteria for generalized anxiety disorder (odds ratio = 2.46). DISCUSSION: Persistent thinness may protect men from eating disorders.

Adult↗
PubMed2004

Evaluation of genetic substructure in the Irish Study of High-Density Schizophrenia Families.

The presence of genetic substructure has the potential to diminish the chances of detecting a linkage signal. Using a Markov chain Monte Carlo procedure developed by Pritchard and colleagues and implemented in the program STRUCTURE, we evaluated the evidence for genetic substructure using genotypes from 37 microsatellite markers in affected individuals selected at random from 263 multiplex families in the Irish Study of High-Density Schizophrenia Families. We found no evidence for the presence of genetic substructure in this sample.

Family↗
PubMed2004

Is risk for alcoholism mediated by individual differences in drinking motivations?

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

Affect↗
PubMed2004

The interrelationship of neuroticism, sex, and stressful life events in the prediction of episodes of major depression.

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

Adult↗
PubMed2004

Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism.

OBJECTIVE: The authors examined the sources of covariation between generalized anxiety disorder and the personality trait of neuroticism. Because women have higher levels of neuroticism and twice the risk of lifetime generalized anxiety disorder of men, gender-specific effects were also explored. METHOD: Lifetime generalized anxiety disorder and neuroticism were assessed in more than 8,000 twins from male-male, female-female, and opposite-sex pairs through structured diagnostic interviews. Sex-limited Cholesky structural equation models were used to decompose the correlations between generalized anxiety disorder and neuroticism into genetic and environmental components, including sex-specific factors. RESULTS: Genetic correlations between generalized anxiety disorder and neuroticism were high and differed (nonsignificantly) between men and women (1.00 and 0.58, respectively). When nonsignificant gender differences were removed from the models, correlations between generalized anxiety disorder and neuroticism were estimated at 0.80 (95% confidence interval=0.52-1.00). The individual-specific environmental correlation between generalized anxiety disorder and neuroticism was estimated at 0.20 for both genders. CONCLUSIONS: There is substantial overlap between the genetic factors that influence individual variation in neuroticism and those that increase liability for generalized anxiety disorder, irrespective of gender. The life experiences that increase vulnerability to generalized anxiety disorder, however, have only modest overlap with those that contribute to an individual's level of neuroticism.

Adult↗
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↗