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Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and multiple sclerosis (MS) (n=43,879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.

Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.

Objective: The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).Method: The family sample included 2,461 individuals from 631 pedigrees (581 in the primary European-ancestry analyses). Association was tested for single SNPs and genetic pathways. Polygenic scores based on family study results were used to predict case-control status in the Schizophrenia Psychiatric GWAS Consortium (PGC) data set, and consistency of direction of effect with the family study was determined for top SNPs in the PGC GWAS analysis. Within-family segregation was examined for schizophrenia-associated rare CNVs.Results: No genome-wide significant associations were observed for single SNPs or for pathways. PGC case and control subjects had significantly different genome-wide polygenic scores (computed by weighting their genotypes by log-odds ratios from the family study) (best p=10(-17), explaining 0.4% of the variance). Family study and PGC analyses had consistent directions for 37 of the 58 independent best PGC SNPs (p=0.024). The overall frequency of CNVs in regions with reported associations with schizophrenia (chromosomes 1q21.1, 15q13.3, 16p11.2, and 22q11.2 and the neurexin-1 gene [NRXN1]) was similar to previous case-control studies. NRXN1 deletions and 16p11.2 duplications (both of which were transmitted from parents) and 22q11.2 deletions (de novo in four cases) did not segregate with schizophrenia in families.Conclusions: Many common SNPs are likely to contribute to schizophrenia risk, with substantial overlap in genetic risk factors between multiply affected families and cases in large case-control studies. Our findings are consistent with a role for specific CNVs in disease pathogenesis, but the partial segregation of some CNVs with schizophrenia suggests that researchers should exercise caution in using them for predictive genetic testing until their effects in diverse populations have been fully studied. [ABSTRACT FROM AUTHOR]

BackgroundPsychiatric conditions in which symptoms arise involuntarily (‘diseases’) might be assumed to be more heritable than those in which choices are essential (behavioral disorders). We sought to determine whether psychiatric ‘diseases’ (Alzheimer's disease, schizophrenia, and mood and anxiety disorders) are more heritable than behavioral disorders (substance use disorders and anorexia nervosa).MethodWe reviewed the literature for recent quantitative summaries of heritabilities. When these were unavailable, we calculated weighted mean heritabilities from twin studies meeting modern methological standards.ResultsHeritability summary estimates were as follows: bipolar disorder (85%), schizophrenia (81%), Alzheimer's disease (75%), cocaine use disorder (72%), anorexia nervosa (60%), alcohol dependence (56%), sedative use disorder (51%), cannabis use disorder (48%), panic disorder (43%), stimulant use disorder (40%), major depressive disorder (37%), and generalized anxiety disorder (28%).ConclusionsNo systematic relationship exists between the disease-like character of a psychiatric disorder and its heritability; many behavioral disorders seem to be more heritable than conditions commonly construed as diseases. These results suggest an error in ‘common-sense’ assumptions about the etiology of psychiatric disorders. That is, among psychiatric disorders, there is no close relationship between the strength of genetic influences and the etiologic importance of volitional processes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Twin studies have suggested that additive genetic factors significantly contribute to liability to bulimia nervosa (BN). However, the diagnostic criteria for BN remain controversial. In this study, an item-factor model was used to examine the BN diagnostic criteria and the genetic and environmental contributions to BN in a population-based twin sample. The validity of the equal environment assumption (EEA) for BN was also tested. METHOD: Participants were 1024 female twins (MZ n=614, DZ n=410) from the population-based Mid-Atlantic Twin Registry. BN was assessed using symptom-level (self-report) items consistent with DSM-IV and ICD-10 diagnostic criteria. Items assessing BN were included in an item-factor model. The EEA was measured by items assessing similarity of childhood and adolescent environment, which have demonstrated construct validity. Scores on the EEA factor were used to specify the degree to which twins shared environmental experiences in this model. RESULTS: The EEA was not violated for BN. Modeling results indicated that the majority of the variance in BN was due to additive genetic factors. There was substantial variability in additive genetic and environmental contributions to specific BN symptoms. Most notably, vomiting was very strongly influenced by additive genetic factors, while other symptoms were much less heritable, including the influence of weight on self-evaluation. These results highlight the importance of assessing eating disorders at the symptom level. CONCLUSIONS: Refinement of eating disorder phenotypes could ultimately lead to improvements in treatment and targeted prevention, by clarifying sources of variation for specific components of symptomatology. [ABSTRACT FROM AUTHOR]

BACKGROUND: Certain personality traits have long been suspected to reflect an enduring vulnerability to major depression (MD) in part because of shared genetic risk factors. Although many have agreed that normative personality is well captured by the 'Big-Five' personality traits of Openness (O), Conscientiousness (C), Extraversion (E), Agreeableness (A) and Neuroticism (N), to date genetically informative studies have only examined the relationship between MD and N and E. METHOD: Questionnaires were completed on a website, yielding a sample of 44 112 subjects including both members of 542 same-sex twin pairs. Personality was measured by the Big Five Inventory. Structural modeling was performed by Mx. RESULTS: Three of the big-five personality traits--O, E and A--had small phenotypic associations with risk for MD and small genetic correlations. Two traits--N and C--had stronger phenotypic associations (positive for N and negative for C) with the following estimates of the genetic correlation with MD: +0.43 for N and -0.36 for C. N and C were moderately negatively correlated. Controlling for N reduced the genetic correlation between C and MD more than controlling for C reduced the genetic correlation between N and MD. CONCLUSIONS: A large proportion of the genetic risk for MD that is expressed via personality is captured by N, with a modest amount due to C, and small amounts from O, E and A. [ABSTRACT FROM AUTHOR]

BACKGROUND: The diagnosis of certain psychiatric syndromes (e.g. panic attacks, post-traumatic stress disorder) is crucially dependent on the psychosocial context in which they arise. For other syndromes (e.g. schizophrenia), the context is generally irrelevant. Should the diagnosis of major depression (MD) be made dependent upon or independent of the psychosocial context in which it occurs? METHOD: Twins were selected from a population-based registry who, on personal interview, reported developing a full depressive syndrome either 'out of the blue' or in response to stressful life events (SLEs) rated objectively as having mild, low moderate, high moderate or severe long-term contextual threat (LTCT). RESULTS: In these depressed subjects, no relationship was found between the level of adversity associated with onset and most indices of liability to depression, including risk of MD in co-twin and parents, level of neuroticism, risk for future depressive episodes, co-morbidity with other internalizing disorders and history of sexual abuse. Compared to the remainder of this epidemiologic cohort, subjects developing depression in response to the severe threat events had substantially elevated levels of all the examined indices of liability to MD. CONCLUSIONS: Individuals who develop a full depressive syndrome in response to high-threat events do not have an appreciably lower liability to MD than those developing depression after exposure to low adversity and have much higher liability to depression than observed in their population cohort. These results support the hypothesis that, in general, MD can be diagnosed independently of the psychosocial context in which it arises. [ABSTRACT FROM AUTHOR]

BACKGROUND: Common fears change over development. Genetic and environmental risk factors for fears are partly shared across fears and partly fear-specific. The nature of the changes in common and fear-specific genetic and environmental risk factors over time is unknown.MethodSelf-reported fears were obtained at ages 13-14, 16-17 and 19-20 from 2404 twins in the Swedish Twin Study of Child and Adolescent Development. A multivariate longitudinal twin analysis was conducted with Mx. RESULTS: Eighteen individual items formed four fear factors: animal, blood-injury, situational, and social. The best-fit model had no quantitative or qualitative sex effects or shared environmental effects, but included a strong common factor with a stable cross-time structure with highest loadings on situational and lowest loadings on social fears. New common and fear-specific genetic risk factors emerged over development. With increasing age, genetic effects declined in overall importance and became more fear-specific. Cross-time continuity in specific genetic effects was highest for animal and lowest for social fears. Social fears had a 'burst' of specific genetic effects in late adolescence. Individual-specific environmental factors impacted both on the general fear factor and on specific fears. Compared to genetic effects, the impact of the unique environment was more time-specific. CONCLUSIONS: Genetic and environmental risk factors for individual fears are partly mediated through a common fear factor and are partly fear-specific in their effect. The developmental pattern of these risk factors is complex and dynamic with new common and specific genetic effects arising in late adolescence and early adulthood. [ABSTRACT FROM AUTHOR]

BACKGROUND: Little is known about the pattern of genetic and environmental influences on symptoms of anxiety and depression (SxAnxDep) from childhood to early adulthood.MethodParental- and self-reported levels of SxAnxDep were assessed at ages 8-9, 13-14, 16-17 and 19-20 years in 2508 twins from the Swedish Twin Study of Child and Adolescent Development (TCHAD). Analysis conducted using the Mx program included SxAnxDep by parental and self-report. RESULTS: The best-fit model revealed one genetic risk factor for SxAnxDep acting at ages 8-9, 13-14, 16-17 and 19-20, and new sets of genetic risk factors 'coming on line' in early adolescence, late adolescence and early adulthood. Together, these genetic factors were very strong influences on the levels of SxAnxDep reported in common by parents and twins with heritability estimates, correcting for rater- and time-specific effects, ranging from 72% to 89%. The first genetic factor, which accounted for 72% of the variance in SxAnxDep at ages 8-9, attenuated sharply in influence, accounting for only 12% of the variance by ages 19-20. No evidence was found for shared environmental influences. Although not statistically significant, the correlation between genetic risk factors for SxAnxDep in males and females declined with advancing age. CONCLUSIONS: Genetic effects on SxAnxDep are developmentally dynamic from middle childhood to young adulthood, demonstrating both genetic innovation and genetic attenuation. The attenuation might explain the low levels of continuity observed for anxiety and depressive disorders from childhood to adulthood. Differences in genetic risk factors for SxAnxDep in males and females may increase during development. [ABSTRACT FROM AUTHOR]

BACKGROUND: The personality disorders (PDs) in the 'dramatic' cluster B [antisocial (ASPD), histrionic (HPD), narcissistic (NPD) and borderline (BPD)] demonstrate co-morbidity. However, the degree to which genetic and/or environmental factors influence their co-occurrence is not known and, with the exception of ASPD, the relative impact of genetic and environmental risk factors on liability to the cluster B PDs has not been conclusively established. METHOD: PD traits were assessed in 1386 Norwegian twin pairs between the age of 19 and 35 years using the Structured Interview for DSM-IV Personality Disorders (SIDP-IV). Using the statistical package Mx, multivariate twin models were fitted to dimensional representations of the PDs. RESULTS: The best-fitting model, which did not include sex or shared family environment effects, included common genetic and environmental factors influencing all four dramatic PD traits, and factors influencing only ASPD and BPD. Heritability was estimated at 38% for ASPD traits, 31% for HPD traits, 24% for NPD traits and 35% for BPD traits. BPD traits had the lowest and ASPD traits the highest disorder-specific genetic variance. CONCLUSION: The frequently observed co-morbidity between cluster B PDs results from both common genetic and environmental influences. Etiologically, cluster B has a 'substructure' in which ASPD and BPD are more closely related to each other than to the other cluster B disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: While the role of genetic factors in self-report measures of emotion has been frequently studied, we know little about the degree to which genetic factors influence emotional facial expressions. METHOD: Twenty-eight pairs of monozygotic (MZ) and dizygotic (DZ) twins from the Minnesota Study of Twins Reared Apart were shown three emotion-inducing films and their facial responses recorded. These recordings were blindly scored by trained raters. Ranked correlations between twins were calculated controlling for age and sex. RESULTS: Twin pairs were significantly correlated for facial expressions of general positive emotions, happiness, surprise and anger, but not for general negative emotions, sadness, or disgust or average emotional intensity. MZ pairs (n=18) were more correlated than DZ pairs (n=10) for most but not all emotional expressions. CONCLUSIONS: Since these twin pairs had minimal contact with each other prior to testing, these results support significant genetic effects on the facial display of at least some human emotions in response to standardized stimuli. The small sample size resulted in estimated twin correlations with very wide confidence intervals. [ABSTRACT FROM AUTHOR]

BACKGROUND: Conduct disorder (CD) and peer deviance (PD) both powerfully predict future externalizing behaviors. Although levels of CD and PD are strongly correlated, the causal relationship between them has remained controversial and has not been examined by a genetically informative study.MethodLevels of CD and PD were assessed in 746 adult male-male twin pairs at personal interview for ages 8-11, 12-14 and 15-17 years using a life history calendar. Model fitting was performed using the Mx program. RESULTS: The best-fit model indicated an active developmental relationship between CD and PD including forward transmission of both traits over time and strong causal relationships between CD and PD within time periods. The best-fit model indicated that the causal relationship for genetic risk factors was from CD to PD and was constant over time. For common environmental factors, the causal pathways ran from PD to CD and were stronger in earlier than later age periods.ConclusionA genetically informative model revealed causal pathways difficult to elucidate by other methods. Genes influence risk for CD, which, through social selection, impacts on the deviance of peers. Shared environment, through family and community processes, encourages or discourages adolescent deviant behavior, which, via social influence, alters risk for CD. Social influence is more important than social selection in childhood, but by late adolescence social selection becomes predominant. These findings have implications for prevention efforts for CD and associated externalizing disorders. [ABSTRACT FROM AUTHOR]

OBJECTIVE: One of the most important controversies regarding depressive personality disorder is the overlap with mood disorders. The aim of this study was to estimate the genetic and environmental sources of covariance between depressive personality disorder and major depressive disorder and to what extent genetic, shared, and unique environmental factors are specific to each disorder. METHOD: A total of 2,801 young adult twins from the Norwegian Institute of Public Health Twin Panel were assessed at personal interview for depressive personality disorder and major depressive disorder with the Structured Interview for DSM-IV Personality and the Composite International Diagnostic Interview. Bivariate Cholesky models were fitted to the data by using the Mx statistical program. RESULTS: In the best-fitting model, the covariation between depressive personality disorder and major depressive disorder were accounted for by genetic and unique environmental factors only. A model that did not include genetic factors specific to major depressive disorder was rejected. The authors found no clear evidence for gender differences in sources of comorbidity of depressive personality disorder and major depressive disorder. CONCLUSIONS: Although depressive personality disorder and major depressive disorder share a substantial proportion of genetic and environmental risk factors, the results from this study support the hypothesis that the two disorders are distinct entities with overlapping, but not identical, etiologies. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: The relationship between personality and psychiatric illness is complex. It is not clear whether one directly causes the other.MethodIn a population-based sample of male twins (n=3030), we attempted to predict major depression (MD) from neuroticism (N) and extraversion (E) and vice versa, to evaluate the causal, scar, state, and prodromal hypotheses. In a longitudinal, structural equation twin model, we decomposed the covariation between N and MD into (a) genetic and environmental factors that are common to both traits, as well as specific to each one and (b) direct causal effects of N at time 1 on subsequent MD, as well as between MD and subsequent N. RESULTS: E was negatively correlated with lifetime and one-year prevalence of MD. N predicted the new onset of MD, and was predicted by both current and past MD. It did not predict the time to onset of MD. All of the covariation between N and MD was due to additive genetic and individual-specific environmental factors shared by both traits and a direct causal path between MD and N assessed later. No genetic factors were unique to either trait. CONCLUSIONS: In men, N may be a vulnerability factor for MD but does not cause it directly. However, MD may have a direct causal effect on N. The genetic overlap between N and MD in men may be greater than in women. [ABSTRACT FROM AUTHOR]

Background. Although an obvious environmental factor influencing drug use, the sources of individual differences in drug availability (DA) are unknown.Method. This report is based on 1788 adult males from the Mid-Atlantic Twin Registry who participated in a structured telephone interview that included retrospective assessments of DA (cigarette, alcohol, marijuana, cocaine and stimulants) between ages 8 and 25. We fitted a biometric dual change score (DCS) model, adapted for ordinal data, to model latent growth and estimate the genetic and environmental components of variance over time.Results. DA, despite being considered an environmental risk factor, is under both genetic and environmental control. For cigarette, alcohol, marijuana and cocaine availability, there was an overall increase in additive genetic variance and a decline in shared environmental variance over time. Non-shared environmental variance remained steady. Stimulant availability did not follow this pattern. Instead, there was an upswing in shared environmental effects with increasing age.Conclusion. We have modeled the genetic and environmental architecture of changes in DA across adolescence. The rise in additive genetic variance over time coincides with acceleration in the expression of individual differences, probably brought on by an increase in personal freedom and a reduction in social constraints. Understanding the etiology of DA is likely to reveal key components, acting directly or indirectly, in the pathway(s) leading to drug initiation, abuse and dependence. [ABSTRACT FROM AUTHOR]

Background. This review tackles the question: 'Is bereavement related depression (BRD) the same or different from standard (non-bereavement-related) major depression (SMD)?' To answer this question, we examined published data on key characteristics that define and characterize SMD to assess whether they also characterize BRD.Method. We searched all English-language reports in Medline up to November 2006 to identify relevant studies. Bibliographies of located articles were searched for additional studies.Results. Consistent with the position that BRD is distinct from SMD, some, but not all, studies report that men are as likely as women to have BRD and that past or family histories of SMD do not predict BRD. With greater consistency, studies suggest that, like SMD, BRD is: more common in younger than in older adults, predicated by poor health or low social support, followed by recurrent episodes of major depressive episode (MDE), and associated with impaired immunological responses, altered sleep architecture, and responsivity to antidepressant treatment.Conclusions. Overall, the prevailing evidence more strongly supports similarities than differences between BRD and SMD. Because so few studies focus on BRD occurring within the first 2 months of bereavement, the period identified by the DSM to exclude the diagnosis of MDE, more research is needed specifically on this group to help us evaluate the validity of this important diagnostic convention. [ABSTRACT FROM AUTHOR]

BACKGROUND: The DSM-IV cluster C Axis II disorders include avoidant (AVPD), dependent (DEPD) and obsessive-compulsive (OCPD) personality disorders. We aimed to estimate the genetic and environmental influences on dimensional representations of these disorders and examine the validity of the cluster C construct by determining to what extent common familial factors influence the individual PDs. METHOD: PDs were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in a sample of 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel (NIPHTP). A single-factor independent pathway multivariate model was applied to the number of endorsed criteria for the three cluster C disorders, using the statistical modeling program Mx. RESULTS: The best-fitting model included genetic and unique environmental factors only, and equated parameters for males and females. Heritability ranged from 27% to 35%. The proportion of genetic variance explained by a common factor was 83, 48 and 15% respectively for AVPD, DEPD and OCPD. Common genetic and environmental factors accounted for 54% and 64% respectively of the variance in AVPD and DEPD but only 11% of the variance in OCPD. CONCLUSION: Cluster C PDs are moderately heritable. No evidence was found for shared environmental or sex effects. Common genetic and individual environmental factors account for a substantial proportion of the variance in AVPD and DEPD. However, OCPD appears to be largely etiologically distinct from the other two PDs. The results do not support the validity of the DSM-IV cluster C construct in its present form. [ABSTRACT FROM AUTHOR]

BACKGROUND: Traditional models of psychiatric epidemiology often assume that the relationship between individuals and their environment is unidirectional, from environment to person. Accumulating evidence from developmental and genetic studies has made this perspective increasingly untenable. METHOD: Literature search using Medline, PsycINFO, article references and contact with experts to identify all papers examining the heritability of measures of environments of relevance to psychiatry/psychology. RESULTS: We identified 55 independent studies organized into seven categories: general and specific stressful life events (SLEs), parenting as reported by child, parenting reported by parent, family environment, social support, peer interactions, and marital quality. Thirty-five environmental measures in these categories were examined by at least two studies and produced weighted heritability estimates ranging from 7% to 39%, with most falling between 15% and 35%. The weighted heritability for all environmental measures in all studies was 27%. The weighted heritability for environmental measures by rating method was: self-report 29%, informant report 26%, and direct rater or videotape observation (typically examining 10 min of behavior) 14%. CONCLUSION: Genetic influences on measures of the environment are pervasive in extent and modest to moderate in impact. These findings largely reflect 'actual behavior' rather than 'only perceptions'. Etiologic models for psychiatric illness need to account for the non-trivial influences of genetic factors on environmental experiences. [ABSTRACT FROM AUTHOR]

BACKGROUND: Personality disorders (PDs) as assessed by questionnaires and personal interviews are heritable. However, we know neither how much unreliability of measurement impacts on heritability estimates nor whether the genetic and environmental risk factors assessed by these two methods are the same. We wish to know whether the same set of PD vulnerability factors are assessed by these two methods. METHOD: A total of 3334 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel (NIPHTP) completed a questionnaire containing 91 PD items. One to 6 years later, 1386 of these pairs were interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV). Self-report items predicting interview results were selected by regression. Measurement models were fitted using Mx. RESULTS: In the best-fit models, the latent liabilities to paranoid personality disorder (PPD), schizoid personality disorder (SPD) and schizotypal personality disorder (STPD) were all highly heritable with no evidence of shared environmental effects. For PPD and STPD, only unique environmental effects were specific to the interview measure whereas both environmental and genetic effects were found to be specific to the questionnaire assessment. For SPD, the best-fit model contained genetic and environmental effects specific to both forms of assessment. CONCLUSIONS: The latent liabilities to the cluster A PDs are highly heritable but are assessed by current methods with only moderate reliability. The personal interviews assessed the genetic risk for the latent trait with excellent specificity for PPD and STPD and good specificity for SPD. However, for all three PDs, the questionnaires were less specific, also indexing an independent set of genetic risk factors. [ABSTRACT FROM AUTHOR]

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

Background. The 'odd' or 'Cluster A' personality disorders (PDs) - paranoid, schizoid and schizotypal PDs - were created in DSM-III with little empirical foundation. We have examined the relationship between the genetic and environmental risk factors for dimensional representations of these three personality disorders.Method. These personality disorders were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel. Using Mx, a single-factor independent pathway twin model was fitted to the number of endorsed criteria for the three disorders.Results. The best-fit model included genetic and unique environmental common factors and genetic and unique environmental effects specific to each personality disorder. Total heritability was modest for these personality disorders and ranged from 21% to 28%. Loadings on the common genetic and unique environmental factors were substantially higher for schizotypal than for paranoid or schizoid PD. The proportion of genetic liability shared with all Cluster A disorders was estimated at 100, 43 and 26% respectively for schizotypal, paranoid and schizoid PDs.Conclusion. In support of the validity of the Cluster A construct, dimensional representations of schizotypal, paranoid and schizoid PD are all modestly heritable and share a portion of their genetic and environmental risk factors. No evidence was found for shared environmental or sex effects for these PDs. Schizotypal PD most closely reflects the genetic and environmental liability common to all three Cluster A disorders. These results should be interpreted in the context of the limited power of this sample. [ABSTRACT FROM AUTHOR]

Substantial advances have been made in recent years in the understanding of the genetic basis of behavior in 'simpler' organisms, especially the mouse and the fruit fly Drosophila. The authors examine the degree of similarity between the genetic underpinnings of psychiatric illness and genetic influences on behavior in such simpler organisms. Six topics are reviewed: 1) the extent of natural genetic variation, 2) the multigenic nature of natural variation, 3) the impact of individual genes on multiple traits, 4) gene-environment interactions, 5) genetic effects on the environment, and 6) gene-by-sex interactions. The results suggest that the pattern of results emerging in psychiatric genetics is generally consistent with the findings of behavioral genetics in simpler organisms. Across the animal kingdom, individual differences in behavior are nearly always influenced by genetic factors which, in turn, result from a substantial number of individual genes, each with a small effect. Nearly all genes that affect behavior influence multiple phenotypes. The impact of individual genes can be substantially modified by other genes and/or by environmental experiences. Many animals alter their environment, and the nature of that alteration is influenced by genes. For some behaviors, the pathway from genes to behavior differs meaningfully in males and females. With respect to the broad patterns of genetic influences on behavior, Homo sapiens appears to be typical of other animal species. [ABSTRACT FROM AUTHOR]