A twin study of generalized anxiety disorder and major depression

Abstract

SYNOPSISPrevious analyses with a sample of female twins sampled from the general population in Virginia have suggested that generalized anxiety disorder (GAD) and major depression (MD) share their genetic determinants but have partly different environmental determinants. The goal of this report is to examine whether these findings apply to samples that include male as well as female twins and contain high proportions of subjects who had been hospitalized for MD.The subjects were ascertained through two different sources: (i) index probands were ascertained through the Swedish Psychiatric Twin Registry for a diagnosis of unipolar or bipolar affective illness; (ii) control twin probands were ascertained through the Swedish Twin Registry. Subjects were sent questionnaires for the assessment of lifetime history of GAD and MD. Positing multinormal distribution of the liability for GAD and MD, we fitted bivariate models to examine the sources of comorbidity.The full model included additive genetic effects, shared environment and individual-specific environment, as well as scalar and non-scalar sex limitations and different thresholds across genders. The best-fitting model included: (i) a genetic correlation of unity; (ii) no common environment; (iii) an individual-specific environmental correlation of 0·28; (iv) different thresholds across genders, but neither scalar nor non-scalar sex-limitations. A model that included additive and dominant genetic effects and individual-specific environment, with correlation of unity for both additive and dominant genetic effects, provided an equivalent fit.These analyses confirm that GAD and MD share the same genetic factors but that their environmental determinants are mostly distinct. Moreover, the present report supports the feasibility of combining clinically ascertained and general-population samples into a single bivariate analysis.

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

“…Furthermore, in univariate analyses, some studies have indicated that genes influencing neuroticism, anxiety and depression are not entirely the same in men and women (Jardine et al 1984 ;Kendler et al 1987Kendler & Prescott, 1999;Fanous et al 2002) and that heritability of neuroticism, anxiety and depression is higher in women than in men (Jardine et al 1984;Bierut et al 1999;Boomsma et al 2000 ;Kendler et al 2001a). However, other studies have found no difference between sexes (Roy et al 1995;Hettema et al 2001 b;Kendler et al 2001 b;Ono et al 2002). It remains to be tested whether different models explain co-morbidity in females and males.…”

“…Studies that have analyzed categorical data (upper part of Table 3) found that, in general, genetic factors overlap more than unique environmental factors, while common environmental factors generally do not overlap (Kendler et al 1992(Kendler et al a, b, 1995Roy et al 1995 ;Kendler, 1996 ;Nelson et al 2000;Scherrer et al 2000;Chantarujikapong et al 2001). MDD and GAD appear to be most closely genetically related with the correlation between the genetic factors varying from 0 .…”

Association of the serotonin transporter gene, neuroticism and smoking behaviours

“…Short forms of two subscales were used from the Mood and Anxiety Symptoms Questionnaire to measure levels of anxious arousal (MASQ-AA), and high positive affect (Watson et al 1995) (MASQ-HPA) (a detailed description is provided in the original GENESiS study; Sham et al 2000). G was developed to represent a score that reflected the 'shared genetic liability' to depression and anxiety because there is evidence to suggest that, at a genetic and clinical level, depression and anxiety are closely related (Kendler et al 1987(Kendler et al , 1992Roy et al 1995). The maximum possible heritability estimate of the composite index in this sample was estimated at 42%, a result comparable to estimates given for neuroticism and depression (Kendler et al 1993a;Sullivan et al 2000).…”

Classical twin studies and beyond

“…27,28 The answers to these questions lie in the cross-twin, cross-trait correlations in MZ versus DZ pairs of twins, such as the correlation of anxiety in one twin with depression in the other twin. Using this design, Neale and Kendler 28 and Roy et al 29 found that co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) is not due to chance or to a third independent disorder, but is probably caused by correlated susceptibilities to the disorders. The model that best explained the association of MD and GAD included a strong genetic correlation (of one) between MD and GAD, and a weak correlation with the individual-specific environment.…”