Biomedical subjects

Carol A Prescott

Publications and source records attributed to Carol A Prescott.

At least 19 recordsLinked to original sources

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

Challenges in genetic studies of the etiology of substance use and substance use disorders: introduction to the special issue.

Misuse of psychoactive substances is associated with substantial costs to users and to society. A growing literature suggests individual differences in vulnerability to develop substance related problems are influenced to a large degree by genetic factors. We review the evidence from genetic epidemiologic and molecular genetic studies of problematic use of alcohol, tobacco, and other drugs, then discuss the challenges for the next generation of studies of genetic influences on substance use. These challenges are addressed in the remaining papers of this special issue. The papers cover a variety of approaches, substances, and non-human as well as human studies, but are united by their focus on going beyond heritability estimates to address the mechanisms and processes underlying the development of substance use and substance related problems, including measurement, precursors of substance abuse, stages of substance involvement, and specificity of genetic influences.

Alcohol Drinking↗

PubMed2006

Effects of genetic and procedural variation on measurement of alcohol sensitivity in mouse inbred strains.

Mice from eight inbred strains were studied for their acute sensitivity to ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction from pre-injection baseline of their body temperature. Two weeks later, mice were tested for their loss of righting reflex (LRR) after a higher dose of ethanol. The LRR was tested using the "classical" method of watching for recovery in animals placed on their backs in a V-shaped trough and recording duration of LRR. In a separate test, naive animals of the same strains were tested for HT repeatedly to assess the development of rapid (RTOL) and chronic tolerance (CTOL). We have recently developed a new method for testing LRR that leads to a substantial increase in the sensitivity of the test. Strains also have been found to differ in the new LRR test, as well as in the development of acute functional tolerance (AFT) to this response. In addition, our laboratory has periodically published strain difference data on the older versions of the HT and LRR responses. The earlier tests used some of the exact substrains tested currently, while for some strains, different substrains (usually, Nih versus Jax) were tested. We examined correlations of strain means to see whether patterns of strain differences were stable across time and across different test variants assessing the same behavioral construct. HT strain sensitivity scores were generally highly correlated across a 10-23 years period and test variants. The CTOL to HT was well-correlated across studies, and was also genetically similar to RTOL. The AFT, however, was related to neither RTOL nor CTOL, although this may be because different phenotypic end points were compared. The LRR data, which included a variant of the classical test, were not as stable. Measures of LRR onset were reasonably well correlated, as were those taken at recovery (e.g., duration). However, the two types of measures of LRR sensitivity to ethanol appear to be tapping traits that differ genetically. Also, the pattern of genetic correlation between HT and LRR initially reported in 1983 was not seen in current and contemporaneous studies. In certain instances, substrain seems to matter little, while in others, substrains differed a great deal. These data are generally encouraging about the stability of genetic differences.

Alcoholism↗

PubMed2006

The impact of generalized anxiety disorder and stressful life events on risk for major depressive episodes.

BACKGROUND: Both generalized anxiety disorder (GAD) and stressful life events (SLEs) are established risk factors for major depressive disorder, but no studies exist that examine the interrelationship of their impact on depressive onsets. In this study, we sought to analyze the joint effects of prior history of GAD and recent SLEs on risk for major depressive episodes, comparing these in men and women. METHOD: In a population-based sample of 8068 adult twins, Cox proportional hazard models were used to predict onsets of major depression from reported prior GAD and last-year SLEs rated on long-term contextual threat. RESULTS: For all levels of threat, prior GAD increases risk for depression, with a monotonic relationship between threat level and risk. While females without prior GAD consistently show higher depressive risk than males, this is no longer the case in subjects with prior GAD who have experienced SLEs. Rather, males appear to be more vulnerable to the depressogenic effects of both prior GAD and SLEs. CONCLUSION: The effects of prior GAD and SLEs jointly increase the risk of depression in both sexes, but disproportionately so in males.

Adult↗

PubMed2006

Identification of susceptibility loci for alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence.

BACKGROUND: Alcoholism is a phenotypically and probably genetically heterogeneous condition. Thus, one strategy for finding genes influencing liability to alcoholism is to study the components of alcoholism, which may be more directly related to the underlying pathophysiology than is clinical diagnosis. The goal of this study was to identify genomic regions containing susceptibility loci for alcohol-related traits. METHODS: A 4-cM dense whole-genome linkage study was conducted in the Irish Affected Sib Pair Study of Alcohol Dependence. Probands, affected siblings, and parents were evaluated by structured interview. Variance component linkage analysis was applied to data from 485 families for 5 measures: initial sensitivity and tolerance (based on scales from the self-report of the effects of ethanol; maximum drinks within 24 hours, an empirically derived factor score based on withdrawal symptoms, and age at onset of alcohol dependence. RESULTS: Evidence for linkage (p<0.005) was found on 9 chromosomes. For age at onset, 2 regions were found on chromosome 9 (highest Lod=2.3, p=0.0005). For initial level of response to alcohol, suggestive regions were on chromosomes 1 and 11 (highest Lod=2.9, p=0.0001 on chromosome 11), while those for tolerance signals were on chromosomes 1, 6, and 22. Maximum drinking was associated with regions on chromosomes 12 and 18. For withdrawal symptoms, the highest peak was on chromosome 2 (Lod=2.2, p=0.0007). CONCLUSIONS: Using quantitative measures of components of alcohol dependence, we identified several regions of the genome that may contain susceptibility loci for specific alcohol-related traits and merit additional study.

Adult↗

PubMed2006

A joint genomewide linkage analysis of symptoms of alcohol dependence and conduct disorder.

BACKGROUND: A large linkage peak for alcohol dependence (AD) was detected on chromosome 4q in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Are the susceptibility genes underlying this peak specific for AD or do they increase risk for externalizing disorders more generally? Can we, in the IASPSAD, replicate prior evidence for linkage to conduct disorder (CD)? METHODS: The 733 all possible sibling pairs in IASPSAD were typed for 1,020 short-tandem-repeat genetic markers. Univariate and bivariate linkage analyses were conducted by the program sequential oligogenic linkage analysis routines (SOLAR), for both the raw and the transformed number of symptoms of AD (ADsx) and number of symptoms of CD (CDsx). In the bivariate analyses, specificity was assessed by the ratio of the variance accounted for in ADsx and CDsx by the quantitative trait locus. RESULTS: In the univariate linkage analyses, no evidence for linkage to CDsx was found under the 4q peak for ADsx and the largest peaks for CDsx were seen on chromosomes 1q (LOD=3.16) and 14p (LOD=2.36). In the bivariate linkage analysis, the 4q peak had high specificity for AD (AD/CD ratio of 39.9). Several smaller peaks, on chromosomes 1, 7, and 10, had moderate specificity for CD but also impacted on risk for AD, with AD/CD ratios of 0.18 to 0.32. CONCLUSIONS: Genes under the 4q linkage peak for AD in the IASPSAD impact specifically on risk for AD rather than more broadly on risk for externalizing syndromes. Suggestive linkages were found in several locations for CD, 2 of which broadly replicate prior findings. The bivariate analyses identified genomic locations containing susceptibility loci that impacted on risk for both CDsx and ADsx.

Alcohol-Related Disorders↗

PubMed2006

A population-based twin study of the relationship between neuroticism and internalizing disorders.

OBJECTIVE: The anxiety and depressive disorders exhibit high levels of lifetime comorbidity with one another. The authors examined how genetic and environmental factors shared by the personality trait neuroticism and seven internalizing disorders may help explain this comorbidity. METHOD: Lifetime major depression, generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal phobia, situational phobia, and neuroticism were assessed in over 9,000 twins from male-male, female-female, and opposite-sex pairs through structured diagnostic interviews. Multivariate structural equation models were used to decompose the correlations between these phenotypes into genetic and environmental components, allowing for sex-specific factors. RESULTS: Genetic factors shared with neuroticism accounted for between one-third and one-half of the genetic risk across the internalizing disorders. When nonsignificant gender differences were removed from the models, the genetic correlations between neuroticism and each disorder were high, while individual-specific environmental correlations were substantially lower. In addition, the authors could identify a neuroticism-independent genetic factor that significantly increased risk for major depression, generalized anxiety disorder, and panic disorder. CONCLUSIONS: There is substantial, but not complete, overlap between the genetic factors that influence individual variation in neuroticism and those that increase liability across the internalizing disorders, helping to explain the high rates of comorbidity among the latter. This may have important implications for identifying the susceptibility genes for these conditions.

Adult↗

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 Washington University Twin Study of alcoholism.

Genetic contributions to the liability to develop alcoholism in males of Northern and Western European ancestry are well-established. However, questions remain concerning the role of genetic variation in the etiology of alcoholism among non-white populations, among women, and the possibility of etiological heterogeneity in subtypes of alcoholism. The answers to these questions are needed to help define phenotypes for molecular genetic studies searching for QTLs for alcoholism. Twins from 295 pairs were consecutively ascertained at inpatient and outpatient psychiatric and alcohol treatment facilities in St. Louis, MO in 1981-1986. Probands and willing cotwins were evaluated by structured psychiatric interviews, psychometric assessment, and lifetime treatment records. One hundred fifty-four probands met criteria for alcohol abuse/dependence (AAD), including twins from 45 MZ, 50 same-sex DZ, and 59 opposite-sex pairs. Twin-pair resemblance was evaluated for AAD and alcohol dependence (AD), as well as for subsets defined by gender, patterns of comorbidity, ethnic background, and clinical features. Among males, heritability of AAD and AD was substantial, with little evidence for common environmental contributions to family resemblance. Pair resemblance among females was also substantial, but similar for MZ and DZ pairs, yielding near-zero heritability estimates. However, based on these sample sizes, the sex differences were not statistically significant. The results confirm prior studies of strong genetic influences on alcoholism in males, but suggest lower genetic influence in females. Power to test other sources of heterogeneity was limited, but the results suggest no evidence for higher heritability for male early onset alcoholism or for alcoholism with comorbid antisocial personality.

Adolescent↗

PubMed2005

The structure of genetic and environmental risk factors for anxiety disorders in men and women.

BACKGROUND: The anxiety disorders exhibit high levels of lifetime comorbidity with one another. Understanding the underlying causes of this comorbidity can provide insight into the etiology of the disorders and inform classification and treatment. OBJECTIVE: To explain anxiety disorder comorbidity by examining the structure of the underlying genetic and environmental risk factors. DESIGN: Lifetime diagnoses for 6 anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal phobia, and situational phobia) were obtained during personal interviews from a population-based twin registry. Multivariate structural equation modeling that allowed for sex differences was performed. SETTING: General community sample. PARTICIPANTS: More than 5000 members of male-male and female-female twin pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. MAIN OUTCOME MEASURES: Parameter estimates for best-fitting model. RESULTS: The full model, which contained 2 common genetic, shared environmental, and unique environmental factors plus disorder-specific factors, could be constrained to equality across male and female study participants. In the best-fitting model, the genetic influences on anxiety were best explained by 2 additive genetic factors common across the disorders. The first loaded most strongly in generalized anxiety disorder, panic disorder, and agoraphobia, whereas the second loaded primarily in the 2 specific phobias. Social phobia was intermediate in that it was influenced by both genetic factors. A small role for shared environmental influences was observed owing to a single common factor that accounted for less than 12% of the total variance for any disorder. Unique environmental influences could be explained by a single common factor plus disorder-specific effects. CONCLUSIONS: The underlying structure of the genetic and environmental risk factors for the anxiety disorders is similar between men and women. Genes predispose to 2 broad groups of disorders dichotomized as panic-generalized-agoraphobic anxiety vs the specific phobias. The remaining associations between the disorders are largely explained by a unique environmental factor shared across the disorders and, to a lesser extent, a common shared environmental factor.

Adult↗

PubMed2005

The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication.

CONTEXT: Prior evidence from twin studies suggested genetic moderation of the depressogenic effects of stressful life events (SLEs). Can the specific genes involved in this effect be identified? OBJECTIVE: To replicate and extend a recent study that a functional variant in the serotonin transporter (5-HTT) might in part explain these findings. DESIGN: Characterizing risk for major depression and generalized anxiety syndrome in the last year as a function of 5-HTT genotype, sex, and the occurrence of SLEs and ratings of the SLE-associated level of threat. SETTING: A population-based sample of adult twins. PARTICIPANTS: Five hundred forty-nine male and female twins with a mean age at participation of 34.9 years (SD 9.1). MAIN OUTCOME MEASURE: Episodes of major depression and generalized anxiety syndrome in the last year with onset measured to the nearest month. RESULTS: Individuals with 2 short (S) alleles at the 5-HTT locus were more sensitive to the depressogenic effects of all SLEs than were those with 1 or 2 long (L) alleles. When level of SLE-associated threat was examined, the interaction between genotype and SLE resulted from an increased sensitivity of SS individuals to the depressogenic effects of common low-threat events. These events had little impact on risk for those possessing the SL and LL genotypes. The 5-HTT genotype did not modify the effects of SLEs on risk for generalized anxiety syndrome. CONCLUSION: Variation at the 5-HTT moderates the sensitivity of individuals to the depressogenic effects of SLEs largely by producing, in SS individuals, an increased sensitivity to the impact of mild stressors. Replication of these intriguing results is needed.

Adult↗

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

Mixed-effects variance components models for biometric family analyses.

Recent substantive research on biometric analyses of twin and family data has used both a biometric path analysis model (PAM) and a biometric variance components model (VCM). Methodological research on these same topics have suggested benefits of using linear structural equation model algorithms (SEMA) as well as mixed effect multilevel algorithms (MEMA). To better understand the potential similarities and differences among these approaches we first highlight the algebraic equivalence between the standard biometric PAM and the corresponding biometric VCM models for family data. Second, we demonstrate how several SEMA programs based on either the PAM or VCM approach produce equivalent estimates for all phenotypic and biometric parameters. Third, we show how the biometric VCM approach (but not the PAM approach) can be easily programmed using current MEMA programs (e.g., SAS PROC MIXED). We then expand the scope of these different approaches to include measured covariates, observed variable interactions and multiple relatives within each family. MEMA software is compared to SEMA software for programming complex models, including the flexibility of data input, treatment of missing data, inclusion of covariates, and ease of accommodating varying numbers of observations (per family or individual).

Algorithms↗

PubMed2005

Genetic and environmental influences on illicit drug use and tobacco use across birth cohorts.

BACKGROUND: The prevalence of use of many psychoactive substances has changed considerably in recent years. While genetic factors impact on overall risk for substance use, we know little about whether the etiological importance of these factors differs across birth cohorts. One theory, which postulates that heritability of deviant traits increases in permissive environments, predicts a positive relationship across cohorts between prevalence and heritability of substance use. METHOD: The lifetime history of use of tobacco, cannabis, cocaine, sedatives and stimulants were assessed in 4826 twins from male-male and female-female pairs born in Virginia from 1934 to 1974. Using empirical methods based on prevalence by birth year, these twins were divided into three cohorts for each substance (e.g. for cannabis 1934-1953, 1954-1968 and 1969-1974). Structural equation modeling was performed using the Mx software package. RESULTS: Prevalence rates for psychoactive substance use differed substantially across cohorts, most markedly for cocaine, sedatives and stimulants, which were highest in the 1958-1963 cohort. However, for all substances, the best-fit model constrained estimates of the etiological role of genetic and environmental risk factors to be equal across both sex and cohort. CONCLUSIONS: We found no evidence in this sample for any systematic relationship between heritability and prevalence of psychoactive substance use--which should be a rough index of drug availability and/or acceptability. This sample had reasonable power to detect large changes in heritability across cohorts and at least moderate power to detect relatively small changes.

Adult↗

PubMed2005

The types of regular cigarette smokers: a latent class analysis.

The present study sought to refine cigarette smoking exposure by examining whether individuals with a history of regular cigarette smoking could be classified into meaningful subgroups based on their smoking habits, nicotine dependence, and quit attempts. Data were obtained from 3,025 male and female twins aged 22-59 years who participated in two longitudinal studies based on the Virginia Twin Registry. Latent class analysis was used to identify the number and nature of subgroups of smokers reporting similar smoking habits based on 18 characteristics. Estimates of prevalence for different classes of smoking were obtained along with expected frequencies of endorsements for each smoking behavior by class. Distributions of demographic characteristics, psychopathology, and personality were examined as external validators. The results demonstrated considerable heterogeneity and revealed eight classes of smokers who differed in their degree of nicotine dependence, cessation attempts, and ability to quit smoking. Smoking classes ranged from individuals who were all former smokers with low nicotine dependence who attempted to quit once and were successful, to individuals who were all current smokers with little desire to quit, to individuals with high nicotine dependence with multiple quit attempts, only a subset of which were successful. Estimates of prevalence for each class were 9%-20%. Our findings support the idea that regular cigarette smokers are highly heterogeneous and highlight the need for smoking exposure refinement in future studies. Acknowledging the complexity of cigarette smoking and classifying smokers into more specific subgroups based on their smoking behavior in future studies will enable more accurate evaluation of disease etiology and risk and could lead to more appropriate smoking cessation interventions.

Adult↗

PubMed2005

The Irish Affected Sib Pair Study of Alcohol Dependence: study methodology and validation of diagnosis by interview and family history.

BACKGROUND: This article is the first report of the Irish Affected Sib Pair Study of Alcohol Dependence, whose goal is to detect the genomic location of susceptibility loci for alcohol dependence (AD). This article describes phenotypic characteristics of the probands, siblings, and parents included in the sample and examines agreement among different sources of diagnostic information, including the validity of family history (FH) assessment. METHODS: Structured diagnostic interviews were conducted with 1414 individuals from 591 families ascertained in Ireland. AD was assessed among 1201 probands and affected siblings with use of the Semi-Structured Assessment for the Genetics of Alcoholism and among 213 parents with use of a modified version of the Structured Clinical Interview for DSM. Probands and siblings were also assessed for drinking history, comorbid disorders, and other clinical characteristics. FH reports based on FH-Research Diagnostic Criteria were obtained for 1113 of these individuals as well as for 3652 first-degree relatives who were not interviewed. RESULTS: Sample characteristics confirm the severity of AD among the affected individuals. Agreement between FH ratings and diagnoses based on direct interviews was high for both parent-offspring and sibling-sibling comparisons (e.g., positive and negative predictive values > 80% for a range of cutoffs). Agreement among individuals about their family members was also high for a single item (1 month or more of drinking problems, tetrachoric r = 0.86-0.98), the total number of DSM-IV AD symptoms (polychoric r = 0.86-0.96), and classifications based on a range of cutoffs (kappa = 0.75-0.80). Use of multiple informants improved classification accuracy only slightly (6-10%). CONCLUSIONS: The authors successfully collected data for a large sample of affected sibling pairs for molecular genetic analysis of AD. Individuals with AD were able to provide accurate evaluations of alcoholism symptoms in their parents and adult siblings. A single screening item performed nearly as well as the full scale. Collecting information from multiple informants may not be cost effective for the gain in predictive accuracy. FH information collected from affected informants can be a valuable source of diagnostic information for family studies of alcoholism.

Adult↗

PubMed2005

Sex differences in the relationship between social support and risk for major depression: a longitudinal study of opposite-sex twin pairs.

OBJECTIVE: Compared to men, women have larger and more intimate social networks and higher rates of major depression. Prior studies have suggested that women are more sensitive to the depressogenic effects of low social support, but most of these studies had substantial methodologic limitations. METHOD: In two interview waves at least 1 year apart, 1,057 pairs of opposite-sex dizygotic twin pairs ascertained from a population-based register were assessed. The authors predicted risk of major depression in the year before the wave 2 interview from levels of social support assessed at wave 1. RESULTS: Women reported higher levels of global social support than their twin brothers. Global social support at wave 1 predicted risk for major depression at wave 2 significantly more strongly in female than in male members of these pairs, and the same effect was seen when the analysis controlled for the history of major depression in the year prior to wave 1. Women were more sensitive than men to the depressogenic effects of low levels of social support, particularly from the co-twin, other relatives, parents, and spouses. Levels of social support did not explain the sex difference in risk for major depression. CONCLUSIONS: Emotionally supportive social relationships are substantially more protective against major depression for women than for men. While these effects cannot explain sex effects on the prevalence of major depression, they do suggest important sex differences in pathways of risk. Clarification of the nature of the causal links between low social support and depression in women is needed.

Adult↗

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↗