RESUMEN
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.
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Alcoholismo/psicología , Trastornos de Ansiedad/psicología , Trastorno Depresivo Mayor/psicología , Sistema de Registros , Gemelos/psicología , Adolescente , Adulto , Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Alcoholismo/genética , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/genética , Comorbilidad , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Femenino , Humanos , Entrevista Psicológica , Modelos Logísticos , Masculino , Noruega/epidemiología , Oportunidad Relativa , Gemelos/genética , Gemelos/estadística & datos numéricos , Gemelos Dicigóticos/genética , Gemelos Dicigóticos/psicología , Gemelos Dicigóticos/estadística & datos numéricos , Gemelos Monocigóticos/genética , Gemelos Monocigóticos/psicología , Gemelos Monocigóticos/estadística & datos numéricos , Adulto JovenRESUMEN
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.
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Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/etiología , Ambiente , Adulto , Edad de Inicio , Trastorno Depresivo Mayor/genética , Femenino , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Herencia Multifactorial , Recurrencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
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.
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Consumo de Bebidas Alcohólicas/genética , Adolescente , Consumo de Bebidas Alcohólicas/prevención & control , Ambiente , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad/genética , Humanos , Estudios Longitudinales , Masculino , Factores de Riesgo , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Adulto JovenRESUMEN
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.
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Manual Diagnóstico y Estadístico de los Trastornos Mentales , Modelos Estadísticos , Trastornos de la Personalidad/clasificación , Adolescente , Adulto , Biometría , Femenino , Humanos , Estudios Longitudinales , Masculino , Noruega/epidemiología , Trastornos de la Personalidad/etiología , Trastornos de la Personalidad/genética , Fenotipo , Factores de Riesgo , Adulto JovenRESUMEN
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.
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Consumo de Bebidas Alcohólicas/genética , Trastornos Relacionados con Alcohol/complicaciones , Trastornos de la Personalidad/complicaciones , Gemelos , Adulto , Trastornos Relacionados con Alcohol/genética , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Noruega , Trastornos de la Personalidad/genética , Medio Social , Adulto JovenRESUMEN
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.
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Trastornos de la Personalidad/genética , Inventario de Personalidad , Personalidad/genética , Adulto , Femenino , Humanos , MasculinoRESUMEN
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.
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Trastornos de Ansiedad/genética , Estudios de Casos y Controles , Estudios de Asociación Genética/métodos , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Población Blanca/genéticaRESUMEN
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.
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Interacción Gen-Ambiente , Trastorno Obsesivo Compulsivo/genética , Trastornos de la Personalidad/genética , Gemelos/genética , Adulto , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Estudios Longitudinales , Masculino , Noruega , Sistema de Registros , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
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.
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Trastorno de Personalidad Antisocial/genética , Trastorno de Personalidad Limítrofe/genética , Enfermedades en Gemelos/genética , Interacción Gen-Ambiente , Adulto , Biometría , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Estudios Longitudinales , Masculino , Noruega , Fenotipo , Factores de Riesgo , Adulto JovenRESUMEN
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.
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Trastornos de Ansiedad/epidemiología , Trastorno Depresivo Mayor/epidemiología , Psiquiatría/clasificación , Gemelos/psicología , Adulto , Ansiedad , Comorbilidad , Depresión , Femenino , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
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.
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Trastornos de Ansiedad/epidemiología , Trastorno de la Conducta/epidemiología , Trastorno Depresivo Mayor/epidemiología , Enfermedades en Gemelos/epidemiología , Responsabilidad Parental/psicología , Trastorno de la Conducta Social/epidemiología , Gemelos Monocigóticos/psicología , Adulto , Autoritarismo , Femenino , Humanos , Estudios Longitudinales , Masculino , Padres/psicología , Psicopatología , Riesgo , Medio Social , Gemelos Monocigóticos/estadística & datos numéricosRESUMEN
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.
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Trastorno Depresivo Mayor/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Adulto , China , Asistencia Sanitaria Culturalmente Competente , Trastorno Depresivo Mayor/etnología , Trastorno Depresivo Mayor/psicología , Europa (Continente) , Femenino , Humanos , Persona de Mediana Edad , Estados UnidosRESUMEN
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.
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Enfermedades en Gemelos/genética , Trastorno de Personalidad Paranoide/genética , Sistema de Registros/estadística & datos numéricos , Trastorno de la Personalidad Esquizotípica/genética , Adolescente , Adulto , Enfermedades en Gemelos/epidemiología , Enfermedades en Gemelos/etiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Noruega/epidemiología , Trastorno de Personalidad Paranoide/epidemiología , Trastorno de Personalidad Paranoide/etiología , Trastorno de la Personalidad Esquizotípica/epidemiología , Trastorno de la Personalidad Esquizotípica/etiología , Adulto JovenRESUMEN
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.
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Agorafobia , Enfermedades en Gemelos , Trastornos Fóbicos , Adulto , Anciano , Agorafobia/epidemiología , Agorafobia/etiología , Agorafobia/genética , Enfermedades en Gemelos/epidemiología , Enfermedades en Gemelos/etiología , Enfermedades en Gemelos/genética , Ambiente , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Trastornos Fóbicos/epidemiología , Trastornos Fóbicos/etiología , Trastornos Fóbicos/genética , Factores de Riesgo , Virginia/epidemiologíaRESUMEN
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.
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Abuso Sexual Infantil/psicología , Trastorno Depresivo Mayor/etiología , Adolescente , Adulto , Abuso Sexual Infantil/estadística & datos numéricos , Trastorno Depresivo Mayor/epidemiología , Enfermedades en Gemelos , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Modelos Estadísticos , Virginia/epidemiología , Adulto JovenRESUMEN
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.
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Trastornos de Ansiedad/genética , Ambiente , Interacción Gen-Ambiente , Medio Social , Adulto , Escolaridad , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Fenotipo , Factores de Riesgo , Gemelos Dicigóticos/genética , Gemelos Dicigóticos/psicología , Gemelos Monocigóticos/genética , Gemelos Monocigóticos/psicologíaRESUMEN
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.
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Trastorno Depresivo Mayor/epidemiología , Enfermedades en Gemelos/epidemiología , Acontecimientos que Cambian la Vida , Estrés Psicológico/epidemiología , Causalidad , Comorbilidad , Trastorno Depresivo Mayor/psicología , Enfermedades en Gemelos/psicología , Femenino , Humanos , Entrevista Psicológica , Estudios Longitudinales , Masculino , Factores de Riesgo , Estrés Psicológico/psicología , Gemelos/psicología , VirginiaRESUMEN
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.
Asunto(s)
Alcoholismo/genética , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Enfermedades en Gemelos/genética , Modelos Estadísticos , Adulto , Alcoholismo/diagnóstico , Enfermedades en Gemelos/diagnóstico , Femenino , Interacción Gen-Ambiente , Humanos , Masculino , Sistema de Registros/estadística & datos numéricos , Factores de Riesgo , Gemelos Dicigóticos/genética , Gemelos Dicigóticos/psicología , Gemelos Monocigóticos/genética , Gemelos Monocigóticos/psicología , Virginia , Población Blanca/genética , Población Blanca/psicologíaRESUMEN
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.