A Population-Based Twin Study of the Relationship Between Neuroticism and Internalizing Disorders

Department of Psychiatry, Virginia Commonwealth University, Ричмонд, Virginia, United States
American Journal of Psychiatry (Impact Factor: 12.3). 06/2006; 163(5):857-64. DOI: 10.1176/appi.ajp.163.5.857
Source: PubMed


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

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Available from: Michael C Neale, Oct 05, 2015
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    • "Anxiety is an all inclusive concept incorporating somatic symptoms (e.g., palpitations, dizziness, dyspnea), emotional and cognitive elements (e.g., negative affect, fear, worry, and rumination ) and behavioral components (e.g., avoidance) (Zebb and Beck, 1998). Additionally, personality traits such as neuroticism are highly comorbid with anxiety disorders (Clark et al., 1994; Hettema et al., 2004, 2006). All of these phenotypes have been the object of extensive research and have been characterized by constructs such as defensive reactivity (Lueken et al., 2013), intolerance of uncertainty (Krain et al., 2008; Simmons et al., 2008), anticipatory apprehension (Nitschke et al., 2009), emotional reactivity (Goldin et al., 2009), emotion regulation (Campbell-Sills et al., 2010), and interoceptive sensitivity (Domschke et al., 2010). "
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    ABSTRACT: Anxiety is an all-inclusive concept incorporating somatic symptoms (palpitations, dizziness, dyspnea), emotional and cognitive elements (negative affect, fear, worry, rumination) and behavioral components (e.g., avoidance). The aim of this study was to examine the specific neural correlates associated with anxiety phenotypes (worry, rumination, somatic anxiety) and negative affect (neuroticism). Twenty-nine anxious participants and 30 healthy controls were included in the study. We analyzed seed-based intrinsic connectivity and used correlation maps in a multivariable regression model to describe the specific effect of each anxiety phenotype independently of the effects of age and the other measures of anxiety. Worry severity was uniquely correlated with increased intrinsic connectivity between right anterior insula (RAI) and the precuneus. Global and somatic anxiety were associated with the limbic and paralimbic structures (increased connectivity between the amygdala, PVN, and hippocampus), while neuroticism was correlated with increased connectivity between limbic and prefrontal structures. Rumination severity did not correlate significantly with any measures of functional connectivity once we controlled for other clinical measures of anxiety. Measures of worry, global anxiety, somatic anxiety, and neuroticism have distinct 'neural signatures'. These results advocate for a fine-grain approach when analyzing the neural substrates of clinical samples with various anxiety disorders.
    Psychiatry Research: Neuroimaging 08/2015; DOI:10.1016/j.pscychresns.2015.08.013 · 2.42 Impact Factor
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    • "The addition of the influences of A, C, and E to the latent unmeasured factor indicate an entity with a basis in both biology and the environment. The factor is thought to be related to the predisposition of the symptom types, a proxy for negative affectivity and distress, and is most likely closely associated with the personality trait neuroticism (Griffith et al. 2010; Hettema et al. 2006). The significant genetic influence on latent factor variance is in line with several previous studies suggesting that genetic sources account for most of the covariance between the traits (Boomsma et al. 2000; Hansell et al. 2012). "
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    ABSTRACT: Somatic complaints in children and adolescents may be considered part of a broader spectrum of internalizing disorders that include anxiety and depression. Previous research on the topic has focused mainly on the relationship between anxiety and depression without investigating how common somatic symptoms relate to an underlying factor and its etiology. Based on the classical twin design with monozygotic and dizygotic twins reared together, our study aimed to explore the extent to which the covariation between three phenotypes in adolescent girls and boys can be represented by a latent internalizing factor, with a focus on both common and specific etiological sources. A population-based sample of twins aged 12–18 years and their mothers and fathers (N = 1394 families) responded to questionnaire items measuring the three phenotypes. Informants' ratings were collapsed using full information maximum likelihood estimated factor scores. Multivariate genetic analyses were conducted to examine the etiological structure of concurrent symptoms. The best fitting model was an ACE com-mon pathway model without sex limitation and with one substantially heritable (44 %) latent factor shared by the phenotypes. Concurrent symptoms also resulted from shared (25 %) and non-shared (31 %) environments. The factor loaded most on depression symptoms and least on somatic complaints. Trait-specific influences ex-plained 44 % of depression variance, 59 % of anxiety variance, and 65 % of somatic variance. Our results suggest the presence of a general internalizing factor along which somatic complaints and mental distress can be modeled. However, specific influences make the symptom types distinguishable.
    Journal of Abnormal Child Psychology 01/2015; DOI:10.1007/s10802-015-9977-y · 3.48 Impact Factor
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    • "Second, there is not an isomorphic relationship between OCS dimensions and underlying genetic factors, but rather, a portion of that risk is shared between them and the rest is dimension-specific. Third, similar to other internalizing symptoms [Jardine et al., 1984] and disorders [Hettema et al., 2006], "
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    ABSTRACT: Individuals with obsessive compulsive disorder can display diverse and heterogeneous patterns of symptoms. Little is known about the relationship between obsessive-compulsive symptom (OCS) dimensions and normal personality traits, particularly those that increase risk for other internalizing disorders. In this study of 1,382 individuals from female–female twin pairs, we examined the relationship between self-report OCS dimensions derived from the Padua Inventory and Eysenck's personality traits neuroticism and extraversion. We conducted factor analysis to determine their phenotypic structure followed by twin analyses to determine their genetic and environmental sources of covariation. A three-factor solution, with dimensions corresponding to checking, aggressive obsessions, and contamination, was the best fit for the Padua OCS items. These dimensions were significantly and somewhat variably associated with neuroticism but negligibly associated with extraversion. The genetic correlations between neuroticism and these three OCS dimensions were moderate to high (0.66 with checking, 0.89 with aggressive obsessions, and 0.40 with contamination). However, the estimated genetic correlation between neuroticism and a unified latent OCS construct was smaller (0.32). Overall this study suggests that genetic, and to a smaller extent environmental, factors underlying neuroticism may act differentially as risk factors for OCS dimensions. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 12/2014; 165(8). DOI:10.1002/ajmg.b.32269 · 3.42 Impact Factor
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