Generalized Anxiety Disorder: Advances in Research and Practice

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  2. A contemporary approach to the research and practice of generalized anxiety disorder.
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Supplementary analyses considered GAD with a shorter minimum duration. Based on the literature, 16 , 24 - 27 , 59 , 60 we examined the following putative risk factors. Family history items were designed using a modified version of the Family History Research Diagnostic Criteria 62 as a model.


Parental disorders were aggregated using a priority hierarchy that was determined following examination of agreement patterns between family history report and available parent interview data. This examination demonstrated the highest agreements regarding parental diagnoses, especially in terms of specificity tends to cause higher bias at T3 compared with T2 and T0. Parent interview information from T1 and T3 interviews was considered to be the most reliable and was used if available.

If parent interview data were not available, T3 family history reports were used, and if these reports were not available, then T2 family history reports and, last, T0 family history reports were used.

In the present study, we consider parental GAD of parents [9. The German version of the Retrospective Self-Report of Inhibition RSRI 63 was used at baseline to assess behavioral inhibition, defined as consistent restraint in response to social and nonsocial situations. The RSRI consists of 30 questions about specific childhood behaviors. Internal consistency of the RSRI was considered acceptable in clinical and nonclinical samples. Validity is high, which is reflected by a strong agreement between individuals self-reports and their parents observer reports regarding the individual's inhibited behaviors as a child, a positive relationship of retrospective self-report and contemporary measures of inhibition, and accounts for variance in general and specific measures of mental health.

The German version of the item Tridimensional Personality Questionnaire 65 was used at T3 to assess 11 subscales that load on 3 distinct dimensions: novelty seeking, reward dependence, and harm avoidance.

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Harm avoidance indicates the tendency toward behavioral inhibition to avoid punishment, novel stimuli, and nonreward. The Tridimensional Personality Questionnaire is based on Cloninger's general theory of personality and is conceptualized to measure stable traits by self-report. Reliability and construct validity of the German version indicate sufficient psychometric properties. A modified German version of the Resilience Scale 68 was used at T1 to assess the degree of individual resilience, defined as a protective personality factor that enhances individual adaptation to high-risk status, acute stressors, or recovery from trauma.

Resilience has been associated with healthy development among children, adolescents, and adults. Early separation events [ Reliability and validity of the Questionnaire of Recalled Parental Rearing Behavior have been reported to be high. The McMaster Family Assessment Device 74 was used at T1 to assess 6 dimensions of family functioning via parental interviews. The general functioning scale is used herein higher scores reflect dysfunctional family functioning , representing the overall family climate.

Reliability and validity of the scale have been established.

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A contemporary approach to the research and practice of generalized anxiety disorder.

Data are weighted by age, sex, and geographic location at baseline to match the distribution of the sampling frame; frequencies numbers are unweighted. Stata statistical software, version Age-specific cumulative incidence rates were estimated with the Kaplan-Meier method in survival analysis. Consistent with prior reports, 47 disorder age of onset was based on the minimum age reported by the respondent at any of the assessment waves.

For the diagnostic outcome categories, the lowest age of onset of the specific disorders was used. All Cox regressions were conducted using age and sex as stratification variables; ie, different curves are fitted according to the values of these variables before assessing the covariates of interest. Some data were missing because of missing age-of-onset information in outcome or time-dependent covariates. The estimated age-specific cumulative incidence for GAD at age 34 is 4.

The cumulative age-of-onset distribution Figure 1 B reveals the earliest onset for anxiety disorders; GAD shows an age-of-onset slope more similar to the depressive than the anxiety disorders, with core incidence periods occurring in adolescence and early adulthood. The considerable degree of heterogeneity among the anxiety disorders should be noted; panic disorder and agoraphobia have a similarly delayed age-of-onset as GAD Figure 1 C.

These patterns contrast with social phobia and particularly specific phobias, for which first onset almost never occurs after adolescence.

Generalized Anxiety Disorder Advances in Research and Practice

Phobias odds ratio, 2. Table 1 presents time-lagged associations between prior and subsequent disorders. Phobias and panic disorder, GAD, and depressive disorders significantly predict the onset of each other. For both directions, the associations of anxiety disorders or GAD with depressive disorders are consistently smaller HRs, 1.

When adjusting for comorbidity with disorders occurring before the outcome, HRs decreased but remained significant, except that the association between prior depressive disorder and subsequent GAD was reduced to nonsignificance. Given the significant associations among disorders, we first examined putative risk factors for any depressive or anxiety disorder, including GAD Table 2. Group A consisted of few cases without lifetime phobias or panic and depressive disorders 15 [ Table 3 shows the frequencies and means for putative risk factors for the 4 diagnostic outcome groups and Table 4 shows the respective associations.

Partly different factors are associated with anxiety alone and depression alone.

Harm avoidance and, less clearly, parental comorbid anxiety and depressive disorders are associated with both anxiety and depressive disorders. However, parental depressive disorders alone, low resilience, low parental emotional warmth, and high parental rejection appear to be specific to offspring depressive disorders; parental GAD, high behavioral inhibition, exposure to childhood separation events, and parental overprotection, in contrast, appear to be specific to anxiety disorders.

The factors associated with GAD overlap with all those that are specific for anxiety disorders parental GAD, behavioral inhibition, childhood separation events, and parental overprotection.

However, they overlap only partly with those that are specific to depressive disorders parental depressive disorders alone. Similar to GAD, comorbid cases with anxiety and depressive disorders reveal a broad range of strong risk associations.

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Since GAD cases group A revealed comorbidity, we repeated the analysis adjusting for comorbid anxiety and depressive disorders with onsets before GAD. Associations for overprotection and family functioning decreased to nonsignificance, likely owing to limited power in the smaller subsample. In supplementary analyses, we explored first whether separation anxiety disorder as an early, childhood-onset disorder is a differential predictor for the 4 diagnostic outcome groups.

Second, we explored the robustness of findings in Tables 3 and 4 by using different outcome definitions. Based on epidemiological evidence suggesting that current criteria for GAD may be too strict, 40 , 79 , 80 particularly for youth, 32 , 51 and given that other studies manipulated the threshold definitions for GAD to increase comparability with major depressive disorder, 17 , 18 , 25 we repeated the analyses using GAD with a shorter minimum duration 3 months and 1 month eTable 1.

When performing analyses using a minimum duration of 3 months for GAD, another indication for risk overlap for GAD and depression was found low resilience. Next, following structural models, we chose to consider in our primary analyses only some of the anxiety disorders, focusing on those with consistent loadings on the fear dimension phobias and panic. Then, contrary to procedures in other studies, 24 , 25 , 38 we considered major depression and dysthymia in our primary analyses following structural 7 , 9 , 10 and comorbidity findings, 32 , 39 - 43 but we chose to exclude bipolar cases because of inconclusive results from structural analyses.

Last, we explored whether the anxiety-specific predictors from Tables 3 and 4 appear consistently across the specific anxiety disorders and GAD without comorbid depression. As shown in Figure 2 , despite some variations, similarly directed risk patterns emerged across the specific anxiety disorders, except that panic disorder without depression was not associated with increased rates of parental GAD. Strong comorbidity between anxiety and depressive disorders raises questions about the need to reconceptualize these disorders, 13 , 14 , 58 , 82 with particularly intense focus on GAD.

The present study contributes novel data relevant to these questions by comparing GAD, other anxiety disorders, and depressive disorders in terms of developmental features and risk factors. Our results suggest some similarities and differences among GAD, other anxiety disorders, and depressive disorders. Although the age-of-onset distribution for GAD appears more similar to depressive disorders than specific and social phobias, panic disorder and agoraphobia also resembled GAD and depression.

Furthermore, temporal comorbidity for GAD showed at least as strong a tie to other anxiety disorders as to depressive disorders. Our findings differentiate patterns for anxiety and depressive disorders, with GAD showing more similarities to anxiety than depression. The diagnosis of GAD first appeared in the DSM-III , 83 when the traditional concept of anxiety neuroses was abandoned in favor of descriptive, phenomenological approaches.

Although originally a residual diagnostic class, GAD gained status as a unique condition based on steadily accumulating evidence. Most prominently, this debate is fueled by data on comorbidity and factor structure, 7 , 9 , 10 , 13 , 14 , 38 , 58 yet other, more substantial work also influences this discussion. Most prior studies compared selected features of GAD and major depression 16 , 24 , 25 without considering relationships to other anxiety disorders. The present study fills this gap by comparing developmental patterns and risk factors among GAD, anxiety disorders, and depressive disorders, including major depression and dysthymia.

Comparing first anxiety disorders alone and then depressive disorders alone, some common risk associations as well as considerable differences were found. For both groups, harm avoidance was an associated factor, and shared familial liability, reflected by parental comorbid anxiety and depression, was indicated. Parental GAD, behavioral inhibition, childhood separation events, and overprotective rearing, however, were specific to anxiety disorders; a history of parental depression alone, low parental emotional warmth, and high degrees of parental rejection were specific to offspring depressive disorders.

These findings are largely consistent with evidence from prior studies suggesting commonalities but also some specificity in the etiopathogenesis of anxiety and depressive disorders. In this context, it should be emphasized that anxiety disorders may themselves be a risk factor for the development of depressive disorders, 2 possibly owing to impairments or other characteristics associated with the respective condition.

Despite indications for the existence of bidirectional associations between anxiety and depressive disorders, mostly owing to the later-onset agoraphobia and panic disorder, this supports the view that anxiety disorders are powerful risk factors for secondary depression as the most frequent trajectory. This is in agreement with findings from many other studies 1 , 51 , 97 - and has led some to suggest that, similar to somatic disorders, staging models may be of potential value for specifying the complexity of developmental patterns of mental disorders.

Against expectations arising from comorbidity and factor-structure findings, our study provides little evidence that GAD is more similar to depressive than anxiety disorders. As in other studies, 24 , 38 , 79 , we do find that GAD and depressive disorders exhibit similar age-of-onset patterns and strong bidirectional associations.