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Background: Genetic risk and environmental adversity-both important risk factors for major depression (MD)-are thought to differentially impact on depressive symptom types and associations. Does heterogeneity in these risk factors result in different depressive symptom networks in patients with MD?, Methods: A clinical sample of 5784 Han Chinese women with recurrent MD were interviewed about their depressive symptoms during their lifetime worst episode of MD. The cases were classified into subgroups based on their genetic risk for MD (family history, polygenic risk score, early age at onset) and severe adversity (childhood sexual abuse, stressful life events). Differences in MD symptom network structure were statistically examined for these subgroups using permutation-based network comparison tests., Results: Although significant differences in symptom endorsement rates were seen in 18.8% of group comparisons, associations between depressive symptoms were similar across the different subgroups of genetic and environmental risk. Network comparison tests showed no significant differences in network strength, structure, or specific edges (P-value > 0.05) and correlations between edges were strong (0.60-0.71)., Limitations: This study analyzed depressive symptoms retrospectively reported by severely depressed women using novel statistical methods. Future studies are warranted to investigate whether similar findings hold in prospective longitudinal data, less severely depressed patients, and men., Conclusions: Similar depressive symptom networks for MD patients with a higher or lower genetic or environmental risk suggest that differences in these etiological influences may produce similar symptom networks downstream for severely depressed women., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To investigate whether diagnostic data from structured interviews, primary care and specialist care registries on major depressive disorder (MDD), anxiety disorders (AD) and alcohol use disorder (AUD) identify the same individuals, yield comparable comorbidity estimates and reflect the same genetic influences., Methods: Registry data from primary and specialist care were available for 11 727 twins and diagnostic interview data for 2271 of these. We used logistic regression analyses and biometric modelling to investigate the overlap between the data sources., Results: Most individuals meeting diagnostic criteria at interview were not registered with a corresponding diagnosis. The rates of registration were higher for MDD (36% in primary care and 15% in specialist care) and AD (21% and 18%) than for AUD (3% and 7%). Comorbidity estimated as odds ratios, but not as polychoric correlations, was higher in the registries than in the interviews. Genetic influences on the disorders were highly correlated across data sources (median r = 0.81), bordering unity for MDD and AD., Conclusion: Prevalence and comorbidity estimates differ between registries and population-based assessment. Nevertheless, diagnoses from health registries reflect the same genetic influences as common mental disorders assessed in the general population, indicating generalizability of aetiological factors across data sources., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The precise nature of how genetic and environmental risk factors influence changes in alcohol use (AU) over time has not yet been investigated. Therefore, the aim of the present study is to examine the nature of longitudinal changes in these risk factors to AU from mid-adolescence through young adulthood. Using a large sample of male twins, we compared five developmental models that each makes different predictions regarding the longitudinal changes in genetic and environmental risks for AU. The best-fitting model indicated that genetic influences were consistent with a gradual growth in the liability to AU, whereas unique environmental risk factors were consistent with an accumulation of risks across time. These results imply that two distinct processes influence adolescent AU between the ages of 15-25. Genetic effects influence baseline levels of AU and rates of change across time, while unique environmental effects are more cumulative.

Background: DSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known., Methods: We use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors., Results: When measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91., Conclusion: The pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs.

Background: A clearer understanding of the etiological overlap between DSM-IV personality disorders (PDs) and alcohol use (AU) and alcohol use disorder (AUD) is needed. To our knowledge, no study has modeled the association between all 10 DSM-IV PDs and lifetime AU and AUD. The aim of the present study is to identify which PDs are most strongly associated with the phenotypic, genetic, and environmental risks of lifetime AU and AUD, and to determine if these associations are stable across time., Methods: Participants were Norwegian twins assessed at two waves. At Wave 1, 2801 twins were assessed for all 10 DSM-IV PD criteria, lifetime AU, and DSM-IV AUD criteria. At Wave 2, six of the 10 PDs were again assessed along with AU and AUD among 2393 twins. Univariate and multiple logistic regressions were run. Significant predictors were further analyzed using bivariate twin Cholesky decompositions., Results: Borderline and antisocial PD criteria were the strongest predictors of AU and AUD across the two waves. Despite moderate phenotypic and genetic correlations, genetic variation in these PD criteria explained only 4% and 3% of the risks in AU, and 5% to 10% of the risks in AUD criteria, respectively. At Wave 2, these estimates increased to 8% and 23% for AU, and 17% and 33% for AUD., Conclusions: Among a large Norwegian twin sample, borderline and antisocial PD criteria were the strongest predictors of the phenotypic and genotypic liability to AU and AUD. This effect remained consistent across time., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Recent work has suggested a high level of congruence between normative personality, most typically represented by the "big five" factors, and abnormal personality traits. In 2,293 Norwegian adult twins ascertained from a population-based registry, the authors evaluated the degree of sharing of genetic and environmental influences on normative personality, assessed by the Big Five Inventory (BFI), and personality disorder traits (PDTs), assessed by the Personality Inventory for DSM-5-Norwegian Brief Form (PID-5-NBF). For four of the five BFI dimensions, the strongest genetic correlation was observed with the expected PID-5-NBF dimension (e.g., neuroticism with negative affectivity [+], conscientiousness with disinhibition [-]). However, neuroticism, conscientiousness, and agreeableness had substantial genetic correlations with other PID-5-NBF dimensions (e.g., neuroticism with compulsivity [+], agreeableness with detachment [-]). Openness had no substantial genetic correlations with any PID-5-NBF dimension. The proportion of genetic risk factors shared in aggregate between the BFI traits and the PID-5-NBF dimensions was quite high for conscientiousness and neuroticism, relatively robust for extraversion and agreeableness, but quite low for openness. Of the six PID-5-NBF dimensions, three (negative affectivity, detachment, and disinhibition) shared, in aggregate, most of their genetic risk factors with normative personality traits. Genetic factors underlying psychoticism, antagonism, and compulsivity were shared to a lesser extent, suggesting that they are influenced by etiological factors not well indexed by the BFI.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs., Competing Interests: The authors declare no conflicts of interest.

Background: The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability., Method: AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits., Results: For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2., Conclusion: Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes.

Background: Mixed anxiety-depression (MAD) has been under scrutiny to determine its potential place in psychiatric nosology. The current study sought to investigate its prevalence, clinical characteristics, course and potential validators., Method: Restricted latent-class analyses were fit to 12-month self-reports of depression and anxiety symptom criteria in a large population-based sample of twins. Classes were examined across an array of relevant indicators (demographics, co-morbidity, adverse life events, clinical significance and twin concordance). Longitudinal analyses investigated the stability of, and transitions between, these classes for two time periods approximately 1.5 years apart., Results: In all analyses, a class exhibiting levels of MAD symptomatology distinctly above the unaffected subjects yet having low prevalence of either major depression (MD) or generalized anxiety disorder (GAD) was identified. A restricted four-class model, constraining two classes to have no prior disorder history to distinguish residual or recurrent symptoms from new onsets in the last year, provided an interpretable classification: two groups with no prior history that were unaffected or had MAD and two with prior history having relatively low or high symptom levels. Prevalence of MAD was substantial (9-11%), and subjects with MAD differed quantitatively but not qualitatively from those with lifetime MD or GAD across the clinical validators examined., Conclusions: Our findings suggest that MAD is a commonly occurring, identifiable syndromal subtype that warrants further study and consideration for inclusion in future nosologic systems.

Background: Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood., Method: DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria., Results: The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points., Conclusion: ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.

Purpose: Consistent and non-specific associations have been found between parenting style and major depression, anxiety disorders, and externalizing behavior. Although often considered part of twins' shared environment, parenting can also be conceptualized as non-shared environment. Non-shared environmental influences have important effects on development but are difficult to test and sort out because of the possible confounding effects of gene-environment interactions and evocative gene-environment correlations. The monozygotic (MZ) differences approach is one way to analytically investigate non-shared environment., Methods: The aim of the present study is to use the MZ differences approach to investigate the relationship between differential parenting among 1303 twin pairs (mean age 36.69 ± 8.56) and differences in total symptom counts of major depression (MD), generalized anxiety disorder (GAD), conduct disorder (CD), and anti-social behavior (ASB) during adulthood., Results: Although effect sizes tended to be small, a number of results were significantly different from zero. Perceived differences in parental coldness was positively associated with internalizing disorders. Differences in protectiveness were negatively associated with MD, GAD, and ASB. Differences in authoritarianism were positively associated with MD and CD, but negatively associated with ASB., Conclusions: Perceived differences in parenting style are associated with differences in MD, GAD, CD, and ASB outcomes in a sample of MZ twins. Despite the lack of a basis for making causal inferences about parenting style and psychopathology, these results are suggestive of such a relationship and show that non-shared environmental influence of parenting does in some cases significantly predict adult psychopathology.

Background: Do DSM-IV diagnostic criteria for major depression (MD) in Chinese and Western women perform in a similar manner?, Method: The CONVERGE study included interview-based assessments of women of Han Chinese descent with treated recurrent MD. Using Mplus software, we investigated the overall degree of between-sample measurement invariance (MI) for DSM-IV diagnostic criteria for MD in the CONVERGE sample and samples selected from four major Western studies from the USA and Europe matched to the inclusion criteria of CONVERGE. These analyses were performed one pair at a time. We then compared the results from CONVERGE paired with Western samples to those obtained when examining levels of MI between pairs of the Western samples., Results: Assuming a single factor model for the nine diagnostic criteria for MD, the level of MI based on global fit indexes observed between the CONVERGE and the four Western samples was very similar to that seen between the Western samples. Comparable results were obtained when using a two-factor structure for MI testing when applied to the 14 diagnostic criteria for MD disaggregated for weight, appetite, sleep, and psychomotor changes., Conclusions: Despite differences in language, ethnicity and culture, DSM criteria for MD perform similarly in Chinese women with recurrent MD and comparable subjects from the USA and Europe. The DSM criteria for MD may assess depressive symptoms that are relatively insensitive to cultural and ethnic differences. These results support efforts to compare findings from depressed patients in China and Western countries.

Background: While cluster A personality disorders (PDs) have been shown to be moderately heritable, we know little about the temporal stability of these genetic risk factors., Method: Paranoid PD (PPD) and schizotypal PD (STPD) were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 twins on average 10 years later at wave 2. Using the program Mx, we fitted a longitudinal latent factor model using the number of endorsed criteria for PPD and STPD., Results: The stability over time of the criteria counts for PPD and STPD, estimated as polychoric correlations, were +0.34 and +0.40, respectively. The best-fit longitudinal model included only additive genetic and individual-specific environmental factors with parameter estimates constrained to equality across the two waves. The cross-wave genetic and individual-specific environmental correlations for a latent cluster A factor were estimated to equal +1.00 and +0.13, respectively. The cross-time correlations for genetic and environmental effects specific to the individual PDs were estimated at +1.00 and +0.16-0.20, respectively. We found that 68% and 71% of the temporal stability of PPD and STPD derived, respectively, from the effect of genetic factors., Conclusion: Shared genetic risk factors for two of the cluster A PDs are highly stable in adults over a 10-year period while environmental risk factors are relatively transient. Over two-thirds of the long-term stability of the common cluster A PD liability can be attributed to genetic influences.

Background: Although prior genetic studies of interview-assessed fears and phobias have shown that genetic factors predispose individuals to fears and phobias, they have been restricted to the DSM-III to DSM-IV aggregated subtypes of phobias rather than to individual fearful and phobic stimuli., Method: We examined the lifetime history of fears and/or phobias in response to 21 individual phobic stimuli in 4067 personally interviewed twins from same-sex pairs from the Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders (VATSPSUD). We performed multivariate statistical analyses using Mx and Mplus., Results: The best-fitting model for the 21 phobic stimuli included four genetic factors (agora-social-acrophobia, animal phobia, blood-injection-illness phobia and claustrophobia) and three environmental factors (agora-social-hospital phobia, animal phobia, and situational phobia)., Conclusions: This study provides the first view of the architecture of genetic and environmental risk factors for phobic disorders and their subtypes. The genetic factors of the phobias support the DSM-IV and DSM-5 constructs of animal and blood-injection-injury phobias but do not support the separation of agoraphobia from social phobia. The results also do not show a coherent genetic factor for the DSM-IV and DSM-5 situational phobia. Finally, the patterns of co-morbidity across individual fears and phobias produced by genetic and environmental influences differ appreciably.

Background: Childhood sexual abuse (CSA) is strongly associated with risk for major depression (MD) but the degree to which this association is causal remains uncertain., Method: We applied structural equation modeling using the Mplus program to 1493 longitudinally assessed female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders., Results: Our model included (i) retrospective self- and co-twin reports on CSA, (ii) major potentially confounding covariates, (iii) assessment of lifetime history of MD at two separate interviews, and (iv) mood-congruent recall (implemented by allowing current depressive symptoms to predict reporting of CSA). In a model with only measurement error, CSA explained 9.6% of MD. Including four key covariates reduced the variance explained to 5.3%, with the largest effects found for parental loss and low parental warmth. Adding the effect of mood-congruent recall to a final well-fitting model reduced the percentage of variance explained in lifetime MD (LTMD) by CSA to 4.4%. In this model, current depressive symptoms significantly predicted recall of CSA., Conclusions: In a model correcting for measurement error, confounding and the impact of mood-congruent recall, CSA remains substantially associated with the risk for LTMD in women. These findings strongly suggest, but do not prove, that this association is causal, and are consistent with previous results in this sample using a co-twin control design, but also indicate that more than half of the uncorrected CSA-MD association is probably not causal. Traumatic life experiences contribute substantially to the risk for LTMD.

To determine the number of genetic factors underlying the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for alcohol dependence (AD), we conducted structural equation twin modeling for seven AD criteria, plus two summary screening questions, in 7133 personally interviewed male and female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, who reported lifetime alcohol consumption. The best-fit twin model required three genetic and two unique environmental common factors, and criterion-specific unique environmental factors. The first genetic factor was defined by high loadings for the probe question about quantity and frequency of alcohol consumption, and tolerance criterion. The second genetic factor loaded strongly on the probe question about self-recognition of alcohol-related problems and AD criteria for loss of control, desire to quit, preoccupation and activities given up. The third genetic factor had high loadings for withdrawal and continued use despite the problems criteria. Genetic factor scores derived from these three factors differentially predicted patterns of comorbidity, educational status and other historical/clinical features of AD. The DSM-IV syndrome of AD does not reflect a single dimension of genetic liability, rather, these criteria reflect three underlying dimensions that index risk for: (i) tolerance and heavy use; (ii) loss of control with alcohol associated social dysfunction and (iii) withdrawal and continued use despite problems. While tentative and in need of replication, these results, consistent with the rodent literature, were validated by examining predictions of the genetic factor scores and have implications for gene-finding efforts in AD.

Background: Previous research has shown that stressful life events (SLEs) influence the pattern of individual depressive symptoms. However, we do not know how these differences arise. Two theories about the nature of psychiatric disorders have different predictions about the source of these differences: (1) SLEs influence depressive symptoms and correlations between them indirectly, via an underlying acute liability to develop a dysphoric episode (DE; common cause hypothesis); and (2) SLEs influence depressive symptoms and correlations between them directly (network hypothesis). The present study investigates the predictions of these two theories., Method: We divided a population-based sample of 2096 Caucasian twins (49.9% female) who reported at least two aggregated depressive symptoms in the last year into four groups, based on the SLE they reported causing their symptoms. For these groups, we calculated tetrachoric correlations between the 14 disaggregated depressive symptoms and, subsequently, tested whether the resulting correlation patterns were significantly different and if those differences could be explained by underlying differences in a single acute liability to develop a DE., Results: The four SLE groups had markedly different correlation patterns between the depressive symptoms. These differences were significant and could not be explained by underlying differences in the acute liability to develop a DE., Conclusions: Our results are not compatible with the common cause perspective but are consistent with the predictions of the network hypothesis. We elaborate on the implications of a conceptual shift to the network perspective for our diagnostic and philosophical approach to the concept of what constitutes a psychiatric disorder.

Objective: To examine the negative statistical relationship between educational level and risk of anxiety disorders, and to estimate to what extent this relationship may be explained by genes or environmental factors influencing both phenotypes., Method: Registry data on educational level for 3339 young adult Norwegian twin pairs and diagnostic data on anxiety disorders for 1385 of these pairs were analysed, specifying structural equations models using MX software., Results: In the best-fitting model, genes accounted for 59% of the variance in education. 18% of the variance was due to environmental factors shared by co-twins, and the remaining 23% due to non-shared environment; 46% of the variance in liability to anxiety disorders was genetic, the remaining variance was due to non-shared environment. A phenotypic polychoric correlation of -0.30 between educational level and 'any anxiety disorder' was estimated to be primarily (83% in the best-fitting model) caused by genes common to the two traits., Conclusion: The relationship between low education and risk of anxiety disorders appears to be primarily determined by genetic effect common to educational level and anxiety disorders., (© 2011 John Wiley & Sons A/S.)

The histidine triad nucleotide-binding protein-1 gene (HINT1) is implicated in schizophrenia and in the behavioral effects of morphine and amphetamine. Because nicotine dependence (ND) is highly comorbid with schizophrenia and other substance abuse, we examined the association of HINT1 with ND. Association analyses from two independent samples show that HINT1 gene variants are associated with ND phenotypes. Furthermore, human postmortem mRNA expression shows that smoking status and genotype influence HINT1 expression in the brain. In animal studies, western blot analyses show an increase of HINT1 protein level in the mouse nucleus accumbens (NAc) after chronic nicotine exposure. This increase was reduced after treatment with the nicotinic-receptor antagonist mecamylamine, and 24 and 72 h after cessation of nicotine treatment. These results indicate a genetic association between HINT1 variants and ND, and indicate that nicotine-induced modulation of HINT1 level may be involved in mechanisms of excess smoking.

Background: Recent behavioral genetic studies have emphasized the importance of investigating eating disorders at the level of individual symptoms, rather than as overall diagnoses. We examined the heritability of binge eating disorder (BED) using an item-factor analytic approach, which estimates contributions of additive genetic (A), common environmental (C), and unique environmental (E) influences on liability to BED as well as individual symptoms., Method: Participants were 614 monozygotic and 410 dizygotic same-sex female twins from the Mid-Atlantic Twin Registry who completed a self-report measure of BED symptoms based upon DSM-IV criteria. Genetic and environmental contributions to BED liability were assessed at the diagnostic and symptom levels, using an item-factor approach., Results: Liability to BED was moderately heritable; 45% of the variance was due to A, with smaller proportions due to C (13%), and E (42%). Additive genetic effects accounted for 29-43% of the variance in individual items, while only 8-14% was due to C., Conclusions: Results highlight the relevance of examining eating disorders at the symptom level, rather than focusing on aggregate diagnoses.

Background: Severity is an important characteristic of major depression (MD) and an 'episode specifier' in DSM-IV classifying depressive episodes as 'mild', 'moderate' or 'severe'. These severity subtypes rely on three different measures of severity: number of criteria symptoms, severity of the symptoms and degree of functional disability. No prior empirical study has evaluated the coherence and validity of the DSM-IV definition of severity of MD., Method: In a sample of 1015 (518 males, 497 females) Caucasian twins from a population-based registry who met criteria for MD in the year prior to interview, factor analysis and logistic regression were conducted to examine the inter-relationships of the three severity measures and their associations with a wide range of potential validators including demographic factors, risk for future episodes, risk of MD in the co-twin, characteristics of the depressive episode, the pattern of co-morbidity, and personality traits., Results: Correlations between the three severity measures were significant but moderate. Factor analysis indicated the existence of a general severity factor, but the factor was not highly coherent. The three severity measures showed differential predictive ability for most of the validators., Conclusions: Severity of MD as defined by the DSM-IV is a multifaceted and heterogeneous construct. The three proposed severity measures reflect partly overlapping but partly independent domains with differential validity as assessed by a wide range of clinical characteristics. Clinicians should probably use a combination of severity measures as proposed in DSM-IV rather than privileging one.

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.

Background: Despite its importance as a paradigmatic personality disorder, little is known about the measurement invariance of the DSM-IV borderline personality disorder (BPD) criteria; that is, whether the criteria assess the disorder equivalently across different groups., Method: BPD criteria were evaluated at interview in 2794 young adult Norwegian twins. Analyses, based on item-response modeling, were conducted to test for differential age and sex moderation of the individual BPD criteria characteristics given factor-level covariate effects., Results: Confirmatory factor analytic results supported a unidimensional structure for the nine BPD criteria. Compared to males, females had a higher BPD factor mean, larger factor variance and there was a significant age by sex interaction on the factor mean. Strong differential sex and age by sex interaction effects were found for the 'impulsivity' criterion factor loading and threshold. Impulsivity related to the BPD factor poorly in young females but improved significantly in older females. Males reported more impulsivity compared to females and this difference increased with age. The 'affective instability' threshold was also moderated, with males reporting less than expected., Conclusions: The results suggest the DSM-IV BPD 'impulsivity' and 'affective instability' criteria function differentially with respect to age and sex, with impulsivity being especially problematic. If verified, these findings have important implications for the interpretation of prior research with these criteria. These non-invariant age and sex effects may be identifying criteria-level expression features relevant to BPD nosology and etiology. Criterion functioning assessed using modern psychometric methods should be considered in the development of DSM-V.

Background: While the family environment can directly influence later risk for psychopathology, dysfunction in the family of origin may also moderate the impact of genetic factors on liability for psychiatric disorders. Can a similar pattern be seen for the personality trait of Neuroticism (N)-which is a risk factor for many psychiatric conditions?, Method: Our sample of 957 complete female-female twin pairs from a population-based register had measures of self-reported N and multiple reporters (twin, co-twin, mother, father) for family dysfunction (FD). Statistical analysis was conducted by traditional regression analysis and a moderator structural equation twin model operationalized in the computer program Mx., Results: Dividing the sample into quartiles based on increasing levels of FD, the mean of N increased substantially while correlations of N in monozygotic (MZ) and dizygotic (DZ) twins were relatively constant. Regression analyses did not suggest greater twin resemblance for N with increasing levels of FD. The best-fit structural equation model was the standard un-moderated model in which the proportion of variance in N due to genetic (39%) and unique environmental effects (61%) remained constant across values of FD., Conclusions: Although a false-negative result due to limited power cannot be excluded, these analyses do not support the hypothesis that FD moderates the impact of genetic factors on levels of N.

Background: Three prior population-based twin studies, none of which was nationally representative, suggested that both genetic and familial-environmental factors contribute to family resemblance for lifetime cannabis use. We seek to replicate these results in a US national probability sample of twin and sibling pairs examining only last year cannabis use., Methods: Cannabis use in the last year was assessed by self-report questionnaire. Biometrical twin analyses were performed., Results: Twin and sibling resemblance for last-year cannabis use was substantial, and much higher in monozygotic pairs than in dizygotic and sibling pairs, where levels of resemblance were similar. Modeling suggested that sibling resemblance was due to genetic factors--with a heritability of at least 60% and probably family environmental factors. No evidence was found that cannabis use was influenced by a special twin environment., Conclusions: Consistent with prior studies, use of cannabis is substantially influenced by genetic factors but family-environment is also possibly of importance.

The association between pregnancy and perinatal complications (PPCs) and risks for adult psychiatric disorders other than psychoses has received relatively limited attention. In this study, we aim to characterize the associations between PPCs and risks for anxiety, affective, substance use, and eating disorders in a population-based sample of twins. Personal interviews were conducted with 1,806 female twin subjects to assess their lifetime history of alcoholism, anorexia nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic disorder, simple phobias, and social phobias. PPCs were retrospectively assessed at personal interview with the subject's parents. The associations between PPCs and risks for psychiatric disorders are characterized using logistic regression. In this sample of twins, gestational age is associated with a significantly increased risk for anorexia nervosa and pregnancy complications are associated with a significantly increased risk for both anorexia nervosa and bulimia nervosa. Pregnancy and perinatal complications may be associated with an increased risk for eating disorders in women., (Copyright 2001 Wiley-Liss, Inc.)

Objective: Although family, twin and adoption studies have suggested that lifetime major depression (MD) is a heritable condition, nearly all these studies have relied for the diagnosis on long-term human memory, which is fallible and potentially biased. Could the estimates of heritability of MD be biased by the well-demonstrated genetic influences on memory?, Methods: Both members of 858 female-female twin pairs from a population-based registry were personally interviewed at least three times over 9 years. The interview assessed a history of depressive onsets and recoveries in the last year to the nearest month. We examine heritability of MD using four recall intervals: last year, last 6 months, last 3 months and current month., Results: Examining the occurrence of one or more depressive episodes across all three interviews, heritabilities of MD (95% CI) for the four time periods were: 0.41 (0.27-0.54), 0.41 (0.26-0.55), 0.35 (0.16-0.52) and 0.34 (0.11-0.55). These heritability estimates did not differ significantly from one another. A similar pattern was found if heritability was assessed for the number of interviews in which criteria for MD were met., Conclusion: Modelling results suggest that the heritability of MD was not influenced by the duration of the required recall. Genetic influences on human recall do not appear to contribute substantially to estimated heritability of MD.

Background: While age-related increases of between-person variability in a variety of cognitive measures are commonly reported in cross-sectional studies, the nature of short-term intraindividual fluctuation in elderly people's performance is relatively unexplored., Objective: The goal of the present study is to examine short-term fluctuations in elderly people's sensorimotor functioning and their relations to individual differences in verbal and spatial memory., Methods: Fluctuations in old adults' (mean = 75.71 years, SD = 6.93 years) sensorimotor performance were investigated by biweekly measurements spanning approximately 7 months. Sensorimotor performance was measured by three walking tasks, including the duration and the number of steps taken to walk a 360-degree circle and to walk 10 feet both at normal and fast pace. Performances of verbal and spatial memory were assessed by weekly measurements of digit memory span, memory for short text and spatial recognition., Results: The magnitude of intraindividual fluctuation in most sensorimotor and memory tasks examined was at least half as great as the level of individual differences across persons. In addition, intraindividual fluctuation in sensorimotor performance is a relatively stable individual attribute, which correlates positively with age and negatively with the levels of sensorimotor, text and spatial memory performance. Although a substantial amount of individual differences in intraindividual fluctuation was shared with mean performance level, variance component and hierarchical regression analyses showed that intraindividual fluctuation in walking steps added significant independent contribution over and above that given by level of performance in predicting text and spatial memory., Conclusion: Taking these results together, we suggest that intraindividual fluctuations in elderly people's performance should not be ignored or simply treated as measurement error; rather, they are potentially important empirical variables for understanding sensory and cognitive aging and the nature of intraindividual response variations in general.

Background: Alcoholism and depression frequently co-occur, but the origins of this comorbidity remain uncertain. Most previous family, twin, and adoption studies of these disorders have used cases ascertained through treatment settings, who may differ from cases in epidemiological samples. We studied the importance of genetic influences on risk for lifetime comorbidity of major depression and alcoholism by means of a population-based twin sample., Methods: Lifetime major depression (MD), alcohol abuse, and alcohol dependence were assessed by structured interview for both members of 3755 twin pairs from the Mid-Atlantic Twin Registry. Pair resemblance was analyzed by means of structural equation models., Results: Individuals with MD were at significantly increased risk for alcohol dependence and for a combined diagnosis of alcohol abuse and/or dependence. History of MD in a twin significantly increased the risk of cotwin alcohol dependence and alcohol abuse and/or dependence among identical male pairs and for alcohol abuse and/or dependence in identical female pairs, but not among male or female fraternal pairs. Results of structural modeling indicate that comorbidity occurs because the genetic and specific environmental sources of liability to MD overlap with those underlying alcohol dependence and alcohol abuse and/or dependence. This overlap was significant only within sex, not across sexes., Conclusions: In this population-based twin sample, the familial transmission of MD and alcohol dependence was largely disorder specific. Comorbidity appears to be due to sex-specific genetic and environmental risk factors. The factors underlying depression in women do not appear to arise from the same factors underlying alcoholism in men.

Background: Some studies suggest that cortisol may be under genetic control. The aims of our study were to investigate the familial resemblance in morning and evening cortisol secretion as assessed by saliva cortisol and to assess the influence of history of major depression., Methods: Women for this investigation were selected from an ongoing study in female-female twin pairs ascertained from the Virginia Twin Registry. Telephone screening assured that current inclusion/exclusion criteria were met. Subjects were asked to collect AM samples within 45 min after awakening, and evening samples immediately before bedtime for 14 days., Results: There was a high degree of correlation across weeks in both the AM and PM cortisol values, indicating significant stability across individuals. There was significant correlation between AM and PM cortisol in monozygotic twins. In twins with a history of major depression (n = 30), compared with the twins without past major depression (n = 28), there was a trend towards higher cortisol (p = .056)., Conclusions: These results suggest that around 40-45% of the total variance in salivary cortisol is shared by monozygotic twins. Although the increase in baseline cortisol in twins with a history of major depression is only significant at the trend level, the effect size is comparable to an "in episode" depressed population.

Background: There are substantial sex differences in all levels of alcohol involvement among U.S. adults. The goal of this study was to test whether the magnitude and sources of genetic and environmental influences on liability for alcohol abuse and dependence differ for men and women., Methods: Structured personal interviews were used to assess DSM-III-R- and DSM-IV-defined alcohol abuse and dependence among 5091 male and 4168 female twins (including 1546 identical, 1128 same-sex fraternal, and 1423 opposite-sex pairs) born in Virginia between 1934 and 1974. Twin correlations were analyzed using structural equation modeling., Results: The magnitude of twin-pair resemblance was similar across several definitions of alcoholism and was substantially higher among identical than fraternal pairs. The proportion of population variation in liability attributed to genetic factors was substantial among both women (55-66%) and men (51-56%), and we found little evidence of a role of environmental factors shared by family members. In all definitions studied, we could reject a model that the genetic sources of liability in the two sexes overlap completely., Conclusion: In this first population-based study of alcoholism among male and female twins from the U.S., we found that genetic factors play a major role in the development of alcoholism in both sexes, that the magnitudes of genetic influence were equally high for men and women, and that the genetic sources of vulnerability are partially, but not completely, overlapping in men and women.