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• We examined the etiologic role of genetic and environmental factors in 14 symptoms of anxiety and depression reported by 3,798 pairs of adult twins from the Australian National Health and Medical Research Council Twin Register. Multifactorlal multiple-threshold models fit the individual symptom scores well. For a substantial majority of the symptoms, the variance in liability was best explained by only genetic factors and environmental influences specific to the individual, where 33% to 46% of the variance was due to genetic factors. For four symptoms, it was not possible to choose definitively between models that, in addition to specific environment, included genetic vs familial environmental effects. These results provide strong evidence for the role of genetic factors in the etiology of symptoms of anxiety and depression as reported in a general population. Evidence for an etiologic role of familial environmental factors was much weaker. If familial environmental factors play any role in the production of these symptoms, they are more important in symptoms of depression than of anxiety, and the factors that predispose to these symptoms are only modestly correlated in males and females.

• Bivariate twin analysis can determine the extent to which two disorders share common genetic, familial environmental, or individual-specific environmental risk factors. We applied this method to lifetime diagnoses of major depression and generalized anxiety disorder as assessed at personal interview in a population-based sample of 1033 pairs of female same-sex twins. Three definitions of generalized anxiety disorder were used that varied in minimum duration (1 vs 6 months) and in the presence or absence of a diagnostic hierarchy. For all definitions of generalized anxiety disorder, the best-fitting twin model was the same. Familial environment played no role in the etiology of either condition. Genetic factors were important for both major depression and generalized anxiety disorder and were completely shared between the two disorders. A modest proportion of the nonfamilial environmental risk factors were shared between major depression and generalized anxiety disorder. Within the limits of our statistical power, our findings suggest that in women, the liability to major depression and generalized anxiety disorder is influenced by the same genetic factors, so that whether a vulnerable woman develops major depression or generalized anxiety disorder is a result of her environmental experiences.

• Little is known about the role of familial and genetic factors in the etiology of generalized anxiety disorder (GAD), a new disorder first proposed in DSM-III. We examine this question in 1033 female-female twin pairs from a population-based registry. Both members in each twin pair were "blindly" assessed by structured psychiatric interview. Our results suggest the following: (1) GAD is a moderately familial disorder; (2) the tendency for GAD to run in families seems to be due largely or entirely to genetic factors shared between relatives rather than to the effects of the familial environment; (3) the heritability of GAD, estimated at around 30%, is modest, with the remainder of the variance in liability resulting from environmental factors not shared by adult twins; (4) the heritability of GAD cannot be explained solely by the occurrence of GAD only during episodes of major depression or panic disorder; and (5) the etiologic role of genetic factors is probably similar in GAD with a 1- vs a 6-month minimum duration of illness.

• In 2163 personally interviewed female twins from a population-based registry, the pattern of age at onset and comorbidity of the simple phobias (animal and situational) — early onset and low rates of comorbidity—differed significantly from that of agoraphobia—later onset and high rates of comorbidity. Consistent with an inherited "phobia proneness" but not a "social learning" model of phobias, the familial aggregation of any phobia, agoraphobia, social phobia, and animal phobia appeared to result from genetic and not from familial-environmental factors, with estimates of heritability of liability ranging from 30% to 40%. The bestfitting multivariate genetic model indicated the existence of genetic and individual-specific environmental etiologic factors common to all four phobia subtypes and others specific for each of the individual subtypes. This model suggested that (1) environmental experiences that predisposed to all phobias were most important for agoraphobia and social phobia and relatively unimportant for the simple phobias, (2) environmental experiences that uniquely predisposed to only one phobia subtype had a major impact on simple phobias, had a modest impact on social phobia, and were unimportant for agoraphobia, and (3) genetic factors that predisposed to all phobias were most important for animal Phobia and least important for agoraphobia. Simple phobias appear to arise from the joint effect of a modest genetic vulnerability and phobia-specific traumatic events in childhood, while agoraphobia and, to a somewhat lesser extent, social phobia result from the combined effect of a slightly stronger genetic influence and nonspecific environmental experiences.

• Although depression aggregates in families, the degree to which this aggregation results from genetic vs environmental factors remains uncertain. We examined this question in 1033 female-female twin pairs from a population-based registry. Both members of each twin pair were "blindly" assessed by structured psychiatric interview. Nine commonly used definitions of major depression, which produced lifetime prevalence rates ranging from 12% to 33%, were examined. For all definitions, the results of model fitting to twin correlations suggested that the liability to depression results from genetic factors and environmental experiences unique to the individual. For seven of the definitions, the estimated heritability of liability was similar, ranging from 33% to 45%. For the two definitions that included only primary cases of depression, the heritability was lower (21% to 24%). The results document that in women (1) genetic factors play a substantial, but not overwhelming, role in the cause of depression; (2) the tendency for depression to aggregate in families results largely from shared genetic and not from shared environmental factors, (3) except for definitions that exclude secondary cases, the magnitude of genetic influence is similar in broadly and narrowly defined forms of major depression, and (4) most environmental experiences of causative importance for depression are those not shared by members of an adult twin pair.

• We examine the relationship between parental loss prior to age 17 years and adult psychopathology in 1018 pairs of female twins from a population-based registry. The relationship between loss and adult psychopathology varied as a function of the kind of loss (death vs separation), the parent involved, and the form of psychopathology. Increased risk for major depression and generalized anxiety disorder was associated with parental separation but not parental death and with separation from either mother or father. Panic disorder was associated with parental death and maternal, but not paternal, separation. Increased risk for phobia was associated with parental death and not parental separation. Risk for eating disorder was unrelated to the experience of parental loss. A model that includes parental loss as a form of "specified" family environment shows that, if it is truly an environmental risk factor for adult psychopatholgic conditions, it can account for between 1.5% and 5.1% of the total variance in liability to these disorders and is responsible for between 7.0% and 20.5% of the tendency for these disorders to aggregate in siblings.

• While traditional multivariate statistical methods can describe patterns of psychiatric symptoms, they cannot provide insight into why certain symptoms tend to co-occur in a population. However, this can be achieved using recently developed methods of multivariate genetic analysis. Examining self-report symptoms in a clinically unselected twin sample (3798 pairs), traditional factor analysis indicates that symptoms of depression and anxiety tend to form separate symptom clusters. Multivariate genetic analysis shows that genes act largely in a nonspecific way to influence the overall level of psychiatric symptoms. No evidence could be found for genes that specifically affect symptoms of depression without also strongly influencing symptoms of anxiety. By contrast, the environment seems to have specific effects, ie, certain features of the environment strongly influence symptoms of anxiety while having little impact on symptoms of depression. These results, which are replicated across sexes, suggest that the separable anxiety and depression symptom clusters in the general population are largely the result of environmental factors.