The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies

Middeldorp, Christel M.; Cath, Daniëlle C.; Dyck, Richard van; Boomsma, Dorret I.

doi:10.1017/s003329170400412x

Cited by 287 publications

(204 citation statements)

References 64 publications

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“…46 A review on the comorbidity between anxiety and depression showed that anxiety and depression might be influenced by shared genes, possibly expressed in the personality trait neuroticism. 17 Linkage findings for neuroticism were summarized by Fullerton et al 47 and do not include findings on chromosome 14 in humans.…”

Section: Discussionmentioning

confidence: 99%

“…11,15 Simple phobia and social phobia have each been investigated once. 9,10 Other anxiety phenotypes 12,14,16 have been based on findings from genetic epidemiological studies indicating a common genetic background for anxiety disorders, 4,17 Thorgeirsson et al 16 considered anxiety disorder or somatoform pain as indicators of affection status. Smoller et al 14 and Kaabi et al 12 constructed new phenotypes of anxiety proneness.…”

Section: Introductionmentioning

confidence: 99%

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Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype

et al. 2007

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Several linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of the Netherlands Twin Register. Genotype and phenotype data were available for 1602 twins and siblings. To estimate identity by descent , additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-regress on the average anxiety scores across time. A linkage signal (logarithm of odds score 3.4, empirical P-value 0.07) was obtained at chromosome 14 for marker D14S65 at 105 cM (90% confidence interval, 99-115 cM bounded by markers D14S1434 and D14S985). This finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might harbor a quantitative trait locus associated with the whole spectrum of general anxiety, that is from the normal to the clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on mouse chromosome 12. Two homolog genes lie in this region -Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future association studies of these genes are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype

et al. 2007

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“…T scores were calculated directly from college-age, sex-specific norms (Robert R McCrae PhD, personal communication, November 14, 2001). Neuroticism (as defined through the NEO) is a well-established, nonspecific risk factor for anxiety and mood disorders (Middeldorp et al, 2005). Given the partial conceptual overlap between AS and N (Cox et al, 1999a;Smoller and Tsuang 1998;Zinbarg et al, 2001), we included neuroticism as a covariate in some models in order to isolate genetic effects more specific to AS.…”

Section: Neo Personality Inventory-revised (Neo-ffi)mentioning

confidence: 99%

Gene-by-Environment (Serotonin Transporter and Childhood Maltreatment) Interaction for Anxiety Sensitivity, an Intermediate Phenotype for Anxiety Disorders

Stein

Schork

Gelernter

2007

Neuropsychopharmacol

204

146

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Anxiety sensitivity (AS) is a dispositional characteristic that predisposes to the development of anxiety disorders (eg, panic and posttraumatic stress disorder) and major depression. AS is subject to genetic and environmental influences, the former as yet unidentified and the latter known to include childhood maltreatment. The serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR) has been associated with depression, but most consistently in the context of environmental stress. We tested the hypothesis that 5-HTTLPR genotype and childhood maltreatment would interact to increase susceptibility to AS in young adults. Subjects were European-American college undergraduates (N ¼ 150, median age 18 years) characterized on a measures of AS (Anxiety Sensitivity Index) and retrospective childhood maltreatment (Childhood Trauma Questionnaire [CTQ]). 5-HTTLPR genotypes were obtained from blood-derived DNA. Linear regression was used to model relationships between 5-HTTLPR, childhood emotional abuse, and AS; covariates such as sex, neuroticism, and ancestral proportion scores were incorporated into some models in a larger, ethnically heterogenous sample (N ¼ 247) to evaluate robustness of the findings to model assumptions. A statistically signficant interaction was observed between levels of childhood emotional (or physical) maltreatment and 5-HTTLPR genotype. Specifically, S/S individuals with higher levels of maltreatment had significantly higher levels of AS than subjects in other groups. No such relationship was found for neuroticism, attesting to the possible specificity of the findings for AS. Findings were consistently robust to the inclusion of covariates, and were not confounded by population stratification. In conclusion, these results provide evidence of a specific genetic influence on anxiety sensitivityFan intermediate phenotype for anxiety (and depressive) disorders; this effect is modified by severity of childhood maltreatment. These findings are consistent with the notion that 5-HTTLPR operates broadly to moderate emotional responsivity to stress.

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“…First, we have taken advantage of the extant literature that suggests shared genetic susceptibility among neuroticism, the anxiety disorders, and major depression (25)(26)(27)(28). Starting with a total of 9270 twin subjects, we used multivariate structural equation modeling to estimate a latent genetic factor for neuroticism that is highly correlated with genetic susceptibility to major depression, generalized anxiety disorder, panic disorder, agoraphobia, and social phobia [see (28) for details].…”

Section: Sample Selectionmentioning

confidence: 99%

Catechol-O-Methyltransferase Contributes to Genetic Susceptibility Shared Among Anxiety Spectrum Phenotypes

Hettema

Bukszár

et al. 2008

Biological Psychiatry

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The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies

Cited by 287 publications

References 64 publications

Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype

Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype

Gene-by-Environment (Serotonin Transporter and Childhood Maltreatment) Interaction for Anxiety Sensitivity, an Intermediate Phenotype for Anxiety Disorders

Catechol-O-Methyltransferase Contributes to Genetic Susceptibility Shared Among Anxiety Spectrum Phenotypes

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