Psychiatry and Clinical Neurosciences 2014; 68:

Psychiatry and Clinical Neurosciences 2014; 68: 712 720 doi:10.1111/pcn.12193 Regular Article Diagnostic utility of worry and rumination: A comparison between generalized anxiety disorder and major depressive disorder Min-Jeong Yang, MA, 1 Bin-Na Kim, MA, 1 Eun-Ho Lee, MA, 2 Dongsoo Lee, MD, PhD, 1 Bum-Hee Yu, MD, PhD, 1 Hong Jin Jeon, MD, PhD 2 and Ji-Hae Kim, PhD 1 * 1 Department of Psychiatry, and 2 Depression Center, Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Aim: Although previous reports have addressed worry and rumination as prominent cognitive processes in generalized anxiety disorder (GAD) and major depressive disorder (MDD) and their distinct correlation with anxious and depressive symptoms, the differential association of worry and rumination with the diagnosis of GAD and MDD remains unclear. The purpose of this study was to investigate the distinct features of worry and rumination in factor structure and their predictive validity for the diagnosis of GAD and MDD. Methods: Four hundred and sixty-eight patients with GAD (n = 148) and MDD (n = 320) were enrolled and the diagnoses were confirmed with the Structured Clinical Interview for DSM-IV. Participants completed the Penn State Worry Questionnaire and Ruminative Response Scale and the severity of anxiety and depressive symptoms was assessed via clinician ratings. Results: In joint factor analysis using the Penn State Worry Questionnaire and Ruminative Response Scale items, worry and rumination emerged as distinct factors. In logistic regression analyses, worry contributed to a higher probability of the diagnosis of GAD than rumination, as rumination did in MDD than worry. Conclusion: This is the first comprehensive study investigating the diagnostic utility of worry and rumination in a well-defined clinical sample of both GAD and MDD. Our results suggest that worry and rumination are distinct cognitive processes and play a differential role in the diagnosis of GAD and MDD, distinguishing them at the cognitive level. Key words: anxiety disorders, cognition, depressive disorder, depressive symptoms, differential diagnosis. THE NOSOLOGIC RELATIONSHIP between generalized anxiety disorder (GAD) and major depressive disorder (MDD) has been a controversial topic, due to high rates of comorbidity and overlapping diagnostic criteria in the DSM-IV. 1,2 In an extensive review, Hettema showed that overall lifetime *Correspondence: Ji-Hae Kim, PhD, Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea. Email: jihae0931.kim@samsung.com Both authors contributed equally to this article. Received 3 September 2012; revised 10 January 2014; accepted 11 April 2014. comorbidities have been reported to be as high as 70 90% and that GAD has substantial overlap with MDD in the areas of genetics, childhood environment, demographics, and personality traits as well as shared pharmacologic efficacy of antidepressants. 3 Despite high comorbidity and similarities between GAD and MDD, some evidence of differences and disorder-specific pathological processes has been reported. 3,4 Among them, worry has been considered to be a key cognitive process that characterizes GAD, whereas rumination has traditionally been related to depression. 5,6 Worry is defined as a chain of thoughts and images, negatively affect-laden and relatively uncontrollable 7 and excessive and uncontrollable 712

Psychiatry and Clinical Neurosciences 2014; 68: 712 720 Worry and rumination 713 worry is the cardinal diagnostic feature of DSM-IV GAD. Studies have pointed out that worry contributes to the maintenance and aggravation of anxiety by interfering with emotional processing. 8 On the other hand, rumination is defined as repetitively focusing one s attention on one s depressive symptoms and on the implications of these symptoms and has been found to be a salient cognitive feature of dysphoria, including MDD. Many studies have provided empirical support for the hypothesis that rumination prolongs and worsens depressed mood and predicts future depressive episodes. 9 However, worry and rumination, although differing in degree, are prevalent in other disorders as well. 10 Furthermore, due to apparent commonalities (e.g., repetitive thoughts in response to negative affect, maintenance or prolongation of pre-existing negative affect), the assertion of a distinctive role of the two constructs has been challenged. Accordingly, recent studies started to investigate the similarities and differences between worry and rumination and their relationship with anxious and depressive symptoms more systematically. Using structural equation modeling, Segerstrom et al. 11 found that both worry and rumination loaded onto a latent variable labeled as repetitive thought and specific factors of worry and rumination failed to differentially relate to anxiety and depression. Fresco et al. 12 reported that worry and rumination are distinct factors in joint factor analysis; however, when their relations to symptoms were examined, both worry and rumination showed an undifferentiated pattern of strong associations with both anxiety and depression, consistent with the study by Segerstrom et al. On the other hand, other joint factor analysis studies controlling for the overlap between worry and rumination in analysis, demonstrated that worry and/or rumination have a differential association with anxiety and depression. 13,14 In summary, results from previous studies converged on the conclusion that both worry and rumination are fairly similar, albeit not identical, cognitive processes, that impact anxiety and depression symptoms. However, methodological limitations prevent greater generalizability of previous findings to a clinical population. Most involved non-clinical student samples 12 14 and in a study including a small clinical sample, the selection depended not on the structured clinical interview but on the self-referral problem. 11 Also, whether worry and rumination are differentially related to the diagnosis of GAD and MDD has not been addressed and thus remains unclear, as previous studies focused only on symptom level in non-clinical samples. To date, no study examined whether two constructs can have differential value in diagnosis in a large patient sample diagnosed via formal structured diagnostic interview. As previous investigations recruited chiefly US or European participants, whether those results can be generalized to a Korean sample is another question that needs to be explored. Prevalence rates of MDD and GAD in East Asian countries, including South Korea, are reported to be lower than those in the West. 15 17 Although explanations for such difference are relatively scant owing to the lack of enough crosscultural studies, different symptom phenomenology might be a factor. Koreans with MDD expressed more symptoms of low energy, concentration difficulty or somatic symptoms and less symptoms of depressed mood. 15 Nevertheless, this does not mean that the DSM criteria are invalid. The DSM MDD in Korea showed good internal consistency and discrimination, but showed a higher diagnostic threshold and different symptom presentations. 15 With regard to GAD, even though the number and content of worry domains were reported to vary crossculturally, cross-cultural similarities in the Penn State Worry Questionnaire (PSWQ) scores indicate equivalent total level of worry across ethnic groups. 16 In the present study, we used the DSM-IV criteria for diagnosis and PSWQ and Ruminative Response Scale (RRS) to assess worry and rumination, all of which are widely utilized measures worldwide and translated and validated in Korean. This study aims to replicate and integrate the current findings and to test the diagnostic utility of worry and rumination in well-defined GAD and MDD patient groups in South Korea. Specifically, we tested the following hypotheses. First, worry and rumination would load onto different latent variables in joint factor analysis, despite a significant correlation. Second, in logistic regression, worry would contribute to a higher probability of the diagnosis of GAD than rumination, while rumination would increase the probability of the diagnosis of MDD than worry. METHODS Participants Four hundred and sixty-eight Korean participants were enrolled at Samsung Medical Center (SMC)

714 M-J. Yang et al. Psychiatry and Clinical Neurosciences 2014; 68: 712 720 Table 1. Demographic variables in GAD and MDD (n = 468) Total sample GAD (n = 148) MDD (n = 320) χ 2 P Age (mean, SD) 49 (15.80) 45.53 (15.15) 50.60 (15.85) 3.26 0.001 Sex Men 162 (34.6%) 55 (37.2%) 107 (33.4%) 1.05 0.592 Women 306 (65.4%) 93 (62.8%) 213 (66.6%) Education Less than elementary school 76 (16.2%) 21 (14.2%) 55 (17.2%) 2.50 0.286 Less than high school 203 (43.4%) 72 (48.6%) 131 (40.9%) Less than graduate school 189 (40.4%) 55 (37.2%) 134 (41.9%) Socioeconomic status Low 28 (6.0%) 7 (4.7%) 21 (6.6%) 7.61 0.179 Below average 64 (13.7%) 21 (14.2%) 43 (13.4%) Average 272 (58.1%) 86 (58.1%) 186 (58.1%) Above average 73 (15.6%) 27 (18.2%) 46 (14.4%) High 14 (3.0%) 6 (4.1%) 8 (2.5%) Missing 17 (3.6%) 1 (0.7%) 16 (5.0%) Statistics for ANOVA. GAD, generalized anxiety disorder; MDD; major depressive disorder. between April 2006 and July 2011. The participants gave written informed consent before participating in the study, which was approved by the Institutional Review Board of SMC. With regard to the ethnicity, although different symptom presentation and relatively lower prevalence were reported in a Korean sample with either MDD or GAD, DSM MDD criteria and the core feature of GAD, which is worry, have been found to be reliable in a Korean sample. 15,16 All participants, therefore, were diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) 18 carried out by a trained clinical psychologist. The primary inclusion criteria were the diagnoses of GAD and MDD. The inclusion criteria for MDD were patients with both single and recurrent episodes, while MDD patients with psychotic features or in full remission, and with comorbid anxiety disorders were excluded. In case of GAD, we decided to include GAD patients with comorbid MDD in order to increase the statistical power of the study, as excluding them would result in a much smaller sample size due to the high comorbidity of GAD and MDD. In order to control the severity of symptoms, we excluded the individuals with Hamilton Anxiety Rating Scale (HAM-A) score of less than 14 in the GAD group and the individuals with Hamilton Depression Scale (HAM-D) score of less than 17 in the MDD group. 19,20 Of the enrolled 468 participants, 148 patients fulfilled the DSM-IV criteria for GAD, and 320 patients fulfilled the DSM-IV criteria for MDD. While there were no significant differences in sex, education level, and socioeconomic status, age was significantly different between the groups (Table 1). In logistic regression, we restricted the scope of analysis to the sample of GAD without MDD (n = 93) in order to make a clear comparison, while the MDD group (n = 320) was still composed of patients only diagnosed with MDD. This means that we excluded GAD patients with comorbid MDD from the GAD group, because these patients with both the diagnoses would confound the differential role of worry and rumination in binary prediction of GAD versus MDD and vice versa. Measures PSWQ The PSWQ is a 16-item self-report scale that assesses the generality, excessiveness, and uncontrollability of pathological worry. 21 Items are rated on a five-point Likert scale and high score (range from 15 to 80) means a more frequent tendency to worry. Lim et al. 22 validated the Korean version (Cronbach s α=0.92). The total PSWQ score is a sum of the scores of positively worded and reversed scores of negatively worded items.

Psychiatry and Clinical Neurosciences 2014; 68: 712 720 Worry and rumination 715 RRS The RRS is a 22-item scale, a subscale of the original Response Style Questionnaire. 23 Each item is rated on a four-point Likert scale with higher total score (range from 22 to 88) indicating more prominent rumination response style. Kim et al. 24 showed good internal consistency, test retest reliability (Cronbach s α=0.89 and 0.59, respectively) of the Korean version. HAM-A The HAM-A is a 14-item clinician rating scale, designed to measure the severity of anxiety symptoms. 25 Items are rated on a four-point Likert scale and the total score ranges from 0 (remission) to 56 (moderate severe). The psychometric properties of the Korean version have been demonstrated by Kim. 26 HAM-D The HAM-D is a 17-item clinician rating scale that assesses the severity of depressive symptoms. 27 The HAM-D total scores range from 0 (remission) to 52 (severe), and higher scores indicate greater depression severity. The Korean version has displayed adequate validity and reliability. 28 Data analysis PASW Statistics 18.0 (SPSS, Chicago, IL, USA) was used for descriptive statistics, χ 2 -test, ANOVA, correlations, and logistic regression analysis. The joint exploratory factor analysis was performed using CEFA 3.04 software. 29 Statistical significance was defined at the 0.05 level, two-tailed. First of all, we performed the joint exploratory factor analysis using items from both the PSWQ and RRS. Maximum likelihood extraction with Quartimax rotation was chosen to allow for the anticipated correlation between factors. We adapted Thurstone s criteria 30 to define a well-loaded item, and the cleanest factor structure was determined if a factor included more than three items. The number of factors was determined by the Eigenvalues greater than 1.0, scree plot and interpretability of the factor. 31 Afterwards, logistic regression analysis was conducted to identify the constructs prognostic of the diagnosis of GAD versus MDD and MDD versus GAD. Total PSWQ and RRS scores were entered simultaneously into an enter model and odds ratios (OR) were adjusted for HAM-A and HAM-D scores. RESULTS General findings Descriptive statistics of PSWQ, RRS, HAM-A, and HAM-D for three groups (GAD without MDD, GAD with MDD, MDD) are presented in Table 2. The results of ANOVA and post-hoc Scheffe s test demonstrated significant differences in all variables between groups. Both the GAD without and with MDD groups showed a greater tendency to worry (PSWQ mean = 62.0, and 65.5, respectively) than the MDD group (PSWQ mean = 57.1; F = 15.214, P < 0.001). Also, the MDD group showed a greater tendency to ruminate (RRS mean = 57.4) than the GAD without MDD group (RRS mean = 49.8; F = 8.327, P < 0.001). Moreover, the GAD with MDD group Table 2. Descriptive statistics and ANOVA for comparison of measures (n = 468) GAD without MDD (n = 93) Mean (SD) GAD with MDD (n = 55) MDD (n = 320) d.f. F P (two-tailed) Post-hoc (Scheffe) PSWQ 62.0 (10.1) 65.5 (10.2) 57.1 (12.0) 2 15.214 <0.001 1,2 > 3 RRS 49.8 (11.2) 56.7 (10.3) 57.4 (12.7) 2 8.327 <0.001 3 > 1 HAM-A 19.4 (3.6) 21.9 (5.0) 19.6 (4.8) 2 6.145 <0.01 2 > 1,3 HAM-D 15.5 (3.8) 19.1 (4.5) 20.9 (3.3) 2 83.991 <0.001 3 > 2 > 1 GAD, generalized anxiety disorder; HAM-A, Hamilton Anxiety Rating Scale; HAM-D, Hamilton Depression Rating Scale; MDD; major depressive disorder; PSWQ, Penn State Worry Questionnaire; RRS, Ruminative Response Scale.

716 M-J. Yang et al. Psychiatry and Clinical Neurosciences 2014; 68: 712 720 showed higher anxiety level (HAM-A mean = 21.9) than the GAD without MDD and the MDD group (HAM-A mean = 19.4, and 19.6, respectively; F = 6.145, P < 0.01) while the MDD group showed higher depression level (HAM-D mean = 20.9) than the GAD with MDD group (HAM-D mean = 19.1), which was found to be more depressed than the GAD without MDD group (HAM-D mean = 15.5; F = 83.991, P < 0.001). To investigate the relationship between measures, we performed a correlation analysis. All measures showed significant positive correlations with each other. In particular, the total PSWQ and RRS scores were positively correlated (r[269] = 0.51, P < 0.001). The PSWQ score was positively correlated with only anxious symptoms (r[418] = 0.24, P < 0.001), while the RRS score showed a mild positive correlation with anxious and depressive symptoms (r[278] = 0.29, P < 0.001 and r[292] = 0.27, P < 0.001, respectively). Joint factor analysis of worry and rumination As the Kaiser Meyer Olkin 32 measure of sampling adequacy was 0.92 and the Bartlett s test of sphericity was significant, χ 2 (703, N = 270) = 5582.86, P < 0.001, our data seemed suitable for factor analysis. Although seven factors with initial Eigenvalue greater than 1 were found, when the scree plot and interpretability of factors were considered, four factors were chosen for further analysis (Table 3). Factor 1 contained 11 PSWQ items and was labeled Worry Engagement. Factor 2 contained five reversed PSWQ items and was labeled Absence of Worry. Factor 3 contained 11 RRS items and was labeled Brooding. Finally, Factor 4 contained eight RRS items and was labeled Reflective Pondering. Three RRS items were dropped, because of cross loading. In general, our results showed a consistent pattern with previous research in which worry was composed of two factors (Worry Engagement, Absence of Worry), and rumination was composed of two factors (Brooding, Reflective Pondering). 5,33 Correlation analysis was additionally performed in order to examine the relationship between derived factors. Factor 1 (Worry Engagement) was positively correlated with Factor 3 (Brooding) and Factor 4 (Reflective Pondering) (r[294] = 0.52, P < 0.001 and r[292] = 0.43, P < 0.001, respectively). Factor 3 (Brooding) was positively correlated with Factor 4 (Reflective Pondering) (r[301] = 0.65, P < 0.001). However, Factor 2 (Absence of Worry), consisting of reversed items of PSWQ, showed no significant correlation with the other factors, which was consistent with the previous study by Lim et al. 22 in which reversed items contributed little to the total score and had low internal consistency. Logistic regression analysis To identify the prognostic construct for the diagnosis of GAD and MDD, we conducted a logistic regression analysis by an enter model. We controlled for anxious and depressive symptoms to elucidate the unique prognostic contribution of worry and rumination above concurrent symptoms. Any demographic variables, however, were not included as they showed no statistically significant contribution in our regression model. After controlling for anxious and depressive symptoms, we computed the total PSWQ and RRS score as predictive variables and then the binary diagnostic groups as dependent variables defining MDD as the reference group. In our analysis model, the global test of significance was highly significant (χ 2 = 118.09, d.f. = 4, P < 0.001). As can be seen in Table 4, after HAM-A and HAM-D scores were controlled for, the total PSWQ score showed an OR greater than 1 (OR, 1.07; 95% confidence interval [CI], 1.02 1.13; P < 0.01) while the OR for the total RRS score was lower than 1 (OR, 0.90; 95%CI, 0.85 0.95; P < 0.001). DISCUSSION This study investigated whether worry and rumination are distinct cognitive processes in terms of construct validity (factor analysis) and predictive validity for diagnosing GAD and MDD. There were two major findings. First, although worry and rumination were substantially correlated with each other, they showed a degree of distinctiveness in the factor solution. Two worry factors (Worry Engagement, Absence of Worry) and two rumination factors (Brooding, Reflective Pondering) were derived by items from either the PSWQ or the RRS without containing items from both the scales. Second, worry was associated with greater odds of receiving a GAD diagnosis than an MDD diagnosis over and above the effect of rumination, whereas rumination was associated with greater odds of receiving an MDD diagnosis than a GAD diagnosis over and above the effect of worry. The current results replicated the findings from previous studies, demonstrating that worry and

Psychiatry and Clinical Neurosciences 2014; 68: 712 720 Worry and rumination 717 Table 3. Joint factor analysis of the PSWQ and the RRS (n = 468) Rotated factor loadings Factor 1 Factor 2 Factor 3 Factor 4 PSWQ 2. My worries overwhelm me 0.68 0.07 0.24 0.12 4. Many situations make me worry 0.73 0.04 0.19 0.13 5. I know I should not worry about things but I just cannot help it 0.67 0.03 0.18 0.05 6. When I am under pressure I worry a lot 0.74 0.02 0.24 0.18 7. I am always worrying about something 0.82 0.02 0.08 0.01 9. As soon as I finish one task, I start to worry about everything else I 0.59 0.03 0.08 0.04 have to do 12. I have been a worrier all my life 0.76 0.05 0.08 0.12 13. I notice that I have been worrying about things 0.80 0.02 0.12 0.14 14. Once I start worrying, I cannot stop 0.78 0.02 0.03 0.08 15. I worry all the time 0.84 0.04 0.09 0.17 16. I worry about projects until they are all done 0.80 0.03 0.05 0.11 1. If I do not have enough time to do everything, I do not worry 0.13 0.33 0.08 0.09 about it 3. I do not tend to worry about things 0.18 0.71 0.16 0.04 8. I find it easy to dismiss worrisome thoughts 0.06 0.49 0.00 0.00 10. I never worry about anything 0.22 0.78 0.11 0.09 11. When there is nothing more I can do about a concern, I do not 0.05 0.47 0.01 0.02 worry about it any more RRS 1. Think about how alone you feel 0.15 0.06 0.39 0.21 2. Think I won t be able to do my job if I don t snap out of this. 0.15 0.05 0.63 0.03 3. Think about your feelings of fatigue and achiness 0.06 0.03 0.53 0.00 4. Think about how hard it is to concentrate 0.07 0.05 0.55 0.08 5. Think What am I doing to deserve this? 0.05 0.06 0.42 0.19 6. Think about how passive and unmotivated you feel 0.07 0.04 0.60 0.09 8. Think about how you don t seem to feel anything anymore 0.02 0.07 0.70 0.04 14. Think I won t be able to concentrate if I keep feeling this way. 0.04 0.04 0.59 0.21 15. Think Why do I have problems other people don t have? 0.04 0.01 0.48 0.32 17. Think about how sad you feel 0.03 0.06 0.46 0.31 19. Think about how you don t feel up to doing anything 0.14 0.02 0.68 0.07 7. Analyze recent events to try to understand why you are depressed 0.01 0.03 0.20 0.49 10. Think Why do I always react this way? 0.08 0.01 0.32 0.49 11. Go away by yourself and think about why you feel this way 0.00 0.04 0.24 0.54 12. Write down what you are thinking and analyze it 0.09 0.05 0.09 0.49 18. Think about all your shortcomings, failings, faults, mistakes 0.17 0.12 0.24 0.38 2. Analyze your personality to try to understand why you are 0.06 0.04 0.08 0.64 depressed 21. Go someplace alone to think about your feelings 0.00 0.06 0.09 0.45 22. Think about how angry you are with yourself 0.02 0.02 0.03 0.56 Dropped items from the RRS 9. Think Why can t I get going? 0.02 0.07 0.40 0.43 13. Think about a recent situation, wishing it had gone better 0.02 0.00 0.30 0.27 16. Think Why can t I handle things better? 0.15 0.05 0.38 0.35 Factor 1, Worry Engagement; Factor 2, Absence of Worry; Factor 3, Brooding; Factor 4, Reflective Pondering; PSWQ, Penn State Worry Questionnaire; RRS, Ruminative Response Scale.

718 M-J. Yang et al. Psychiatry and Clinical Neurosciences 2014; 68: 712 720 Table 4. Logistic regression analysis predicting diagnosis of GAD and MDD (n = 413) Predicted variable β Wald s χ 2 d.f. P Odds ratio (95%CI) Reference Group: MDD HAM-A 0.30 16.21 1 <0.001 1.35 (1.17 1.57) HAM-D 0.89 37.11 1 <0.001 0.41 (0.31 0.55) PSWQ 0.07 7.36 1 <0.01 1.07 (1.02 1.13) RRS 0.11 14.30 1 <0.001 0.90 (0.85 0.95) Odds ratio was controlled for HAM-A and HAM-D. CI, confidence interval; GAD, generalized anxiety disorder; HAM-A, Hamilton Anxiety Rating Scale; HAM-D, Hamilton Depression Rating Scale; MDD, major depressive disorder; PSWQ, Penn State Worry Questionnaire; RRS, Ruminative Response Scale. rumination are related but distinct cognitive processes that are related to both anxiety and depression. 5,12,33,34 In addition, the present study revealed that self-reported worry and rumination may play a differential role in the diagnosis of GAD and MDD. To the best of our knowledge, this is the first study to examine the diagnostic relevance of worry and rumination in a clinical sample by means of logistic regression analyses. The prognostic effects of worry and rumination measured by questionnaires remained significant even after controlling for anxious and depressive symptoms. In other words, self-reported worry and rumination could possibly account for unique variance in the diagnosis beyond that accounted for by concurrent symptoms, thereby suggesting their relative importance as predictors. From the perspective of transdiagnostic processes, which have recently gained growing interest, repetitive negative thinking is a common process present across a large range of Axis I disorders (e.g., rumination, worry, obsession). However, studies suggest that there exists a disorder-specific content in that common process. 10,35 In particular, the finding that worry and rumination retain distinctive features that have implications for diagnosis is consistent with the view that suggested that different contents of repetitive thought may underpin differential mechanisms by which worry and rumination lead to the maintenance of GAD and MDD. 14,36 The content of thinking style has been considered important in differential diagnosis of psychiatric disorders. The contents of worry and rumination differ in terms of predominant theme and timeorientation. 11,37 GAD patients usually focus on negative things that might happen in the future with the aim to avoid or prevent anticipated danger or reduce uncertainty whereas depressive patients typically ruminate about negative things (e.g., loss, failure) that happened in the past in an attempt to establish understanding and meaning. 38 This distinction between worry and rumination reflects a basic difference in the cognitive process of anxiety and depression. With regard to the nosologic relationship, this suggests that GAD and MDD might be distinguished at the cognitive level, and thus provides suggestive evidence more in favor of the current DSM-IV classification of GAD in the category of anxiety disorders, as opposed to reclassifying GAD in the same category as MDD. 4 Also, delineating cognitive processes and contents that have stronger association with certain diagnosis can help us identify the mechanisms that are more central in the development, maintenance, and remission of psychiatric disorders. 35 This has clinical implications for treatment programs. Treatments targeting worry or rumination showed promising outcomes and addition of a cognitive process-focused component to the treatment as usual proved to improve the symptoms, especially in residual or recurrent cases. 39,40 There are also some limitations in this study that should be noted. First, one may argue whether the GAD group is a representative sample of GAD due to the high rate of comorbidity with MDD. Other than the practical difficulty of identifying pure GAD cases and the purpose of increasing the statistical power, our GAD group sampling, which does not artificially eliminate comorbidity with MDD, has some ecological validity. Previous studies have consistently shown high comorbidity with MDD in GAD, 41 and, in a comorbid sample, GAD tended to temporally precede the first episode of MDD and GAD was a

Psychiatry and Clinical Neurosciences 2014; 68: 712 720 Worry and rumination 719 predictor of subsequent depression. 42 44 Second, although our results suggest that worry and rumination may reflect different mechanisms that underpin psychopathology of GAD and MDD, variables, including the derived four factors, that could elucidate those mechanisms were not included in this study. Recent studies have proposed moderating or mediating factors between worry or rumination and anxious or depressive symptoms, such as cognitive bias 45 or coping behaviors. 14 In future research, it is necessary to explore the complex pattern, including the above factors, in clinical samples by adopting structural equation modeling. Third, the result of the joint factor analysis may reflect not only difference in latent constructs but also artifacts, such as scale construction (e.g., wording of items, response category). Although the current results cannot directly rule out this alternative explanation, the fact that no items cross-loaded both on PSWQ and RRS despite significant correlation and that separate factor solutions have been consistently replicated across different samples 12,13,34 implies presence of distinct constructs. Fourth, this study did not compare clinical groups with any other control groups due to the primary aim of this study. Therefore, by including control groups, worry and rumination could get stronger evidence of prognostic utility in diagnosing GAD and MDD in future studies. Lastly, the use of self-report measures and monoethnic composition of the sample may limit the generalizability of the current findings. Future studies utilizing additional experimental measures or other cultural samples would be beneficial. Nonetheless, to the best of our knowledge, this is the first comprehensive study investigating the diagnostic utility of self-reported worry and rumination in both GAD and MDD diagnosed via a structured diagnostic interview. Our results suggest that worry and rumination are related but distinctive cognitive processes and may play a differential role in the diagnosis of GAD and MDD. ACKNOWLEDGMENT The authors do not have any conflicts of interest. REFERENCES 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington, DC, 1994. 2. Kessler RC, Chiu WT, Demler OD, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication. Arch. Gen. Psychiatry 2005; 62: 612 627. 3. Hettema JM. The nosologic relationship between generalized anxiety disorder and major depression. Depress. Anxiety 2008; 25: 300 316. 4. Mennin DS, Heimberg RG, Fresco DM, Ritter MR. Is generalized anxiety disorder an anxiety or mood disorder? Considering multiple factors as we ponder the fate of GAD. Depress. Anxiety 2008; 25: 289 299. 5. Treynor W, Gonzales R, Nolen-Hoeksema S. Rumination reconsidered: A psychometric analysis. Cognit. Ther. Res. 2003; 27: 247 259. 6. Chelminski I, Zimmerman M. Pathological worry in depressed and anxious patients. J. Anxiety Disord. 2003; 17: 533 546. 7. Borkovec TD, Robinson E, Pruzinsky T, DePree JA. Preliminary exploration of worry: Some characteristics and processes. Behav. Res. Ther. 1983; 21: 9 16. 8. Borkovec TD, Inz J. The nature of worry in generalized anxiety disorder: A predominance of thought activity. Behav. Res. Ther. 1991; 28: 153 158. 9. Nolen-Hoeksema S. The role of rumination in depressive disorders and mixed anxiety/depressive symptoms. J. Abnorm. Psychol. 2000; 109: 504 511. 10. Ehring T, Watkins ER. Repetitive negative thinking as a transdiagnostic process. Int J Cognit Ther 2008; 1: 192 205. 11. Segerstrom SC, Tsao JCI, Alden LE, Craske MG. Worry and rumination: Repetitive thought as a concomitant and predictor of negative mood. Cognit. Ther. Res. 2000; 24: 671 688. 12. Fresco DM, Frankel AN, Mennin DS, Turk CL, Heimberg RG. Distinct and overlapping features of rumination and worry: The relationship of cognitive production to negative affective states. Cognit. Ther. Res. 2002; 26: 179 188. 13. Muris P, Roelofs J, Meesters C, Boomsma P. Rumination and worry in nonclinical adolescents. Cognit. Ther. Res. 2004; 28: 539 554. 14. Hong RY. Worry and rumination: Differential associations with anxious and depressive symptoms and coping behavior. Behav. Res. Ther. 2007; 45: 277 290. 15. Chang SM, Hahm B-J, Lee J-Y et al. Cross-national difference in the prevalence of depression caused by the diagnostic threshold. J. Affect. Disord. 2008; 106: 159 167. 16. Lewis-Fernández R, Hinton DE, Laria AJ et al. Culture and the anxiety disorders: Recommendations for DSM-V. Depress. Anxiety 2010; 27: 212 229. 17. Ohayon MM, Hong S-C. Prevalence of major depressive disorder in the general population of South Korea. J. Psychiatr. Res. 2006; 40: 30 36. 18. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders. American Psychiatric Press, Inc, Washington, DC, 1996.

720 M-J. Yang et al. Psychiatry and Clinical Neurosciences 2014; 68: 712 720 19. Bandelow B, Baldwin DS, Dolberg OT, Anderson HF, Stein DJ. What is threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder? J. Clin. Psychiatry 2006; 67: 1428 1434. 20. Shelton RC, Prakash A, Mallinckrodt CH et al. Patterns of depressive symptom response in duloxetine-treated outpatients with mild, moderate or more severe depression. Int. J. Clin. Pract. Suppl. 2007; 61: 1337 1348. 21. Meyer TJ, Miller ML, Metzger RL, Borkovec TD. Development and validation of the Penn State Worry Questionnaire. Behav. Res. Ther. 1990; 28: 487 495. 22. Lim Y-J, Kim Y-H, Lee E-H, Kwon S-M. The Penn State Worry Questionnaire: Psychometric properties of the Korean version. Depress. Anxiety 2008; 25: E97 E103. 23. Nolen-Hoeksema S, Morrow J. A prospective study of depression and posttraumatic stress symptoms after a natural disaster: The 1989 Loma Prieta earthquake. J. Pers. Soc. Psychol. 1991; 61: 115 121. 24. Kim SJ, Kim JH, Youn SC. Validation of the Korean- Ruminative Response Scale (K-RRS). Korean J Clin Psychol 2010; 29: 1 19. 25. Hamilton M. The assessment of anxiety states by rating. Br. J. Med. Psychol. 1959; 32: 50 55. 26. Kim CY. Psychiatric Assessment Instruments. Hana Medical Books, Seoul, 2000. 27. Hamilton M. Development of a rating scale for primary depressive illness. Br. J. Soc. Clin. Psychol. 1967; 6: 278 296. 28. Yi JS, Bae SO, Ahn YM et al. Validity and reliability of the Korean version of the Hamilton Depression Rating Scale (K-HDRS). J. Korean Neuropsychiatr. Assoc. 2005; 44: 456 465. 29. Browne MW, Cudeck R, Tateneni K, Mels G. CEFA: Comprehensive exploratory factor analysis, version 3.03. 2008 [Computer software and manual]. [Cited 15 May 2014.] Available from URL: http://faculty.psy.ohio-state.edu/ browne/software.php 30. Thurstone LL. Multiple Factor Analysis. University of Chicago Press, Chicago, 1947. 31. Tabachnick BG, Fidell LS. Using Multivariate Statistics. Allyn & Bacon, Boston, 2006. 32. Kaiser H. An index of factorial simplicity. Psychometrika 1974; 39: 32 36. 33. Fresco DM, Heimberg RG, Mennin DS, Turk CL. Confirmatory factor analysis of the Penn State Worry Questionnaire. Behav. Res. Ther. 2002; 40: 313 323. 34. Goring HJ, Papageorgiou C. Rumination and worry: Factor analysis of self-report measures in depressed participants. Cognit. Ther. Res. 2008; 32: 554 566. 35. Aldao A, Nolen-Hoeksema S, Schweizer S. Emotionregulation strategies across psychopathology: A metaanalytic review. Clin. Psychol. Rev. 2010; 30: 217 237. 36. Watkins E. Appraisals and strategies associated with rumination and worry. Pers. Individ. Dif. 2004; 37: 679 694. 37. Watkins E, Moulds M, Mackintosh B. Comparisons between rumination and worry in a non-clinical population. Behav. Res. Ther. 2005; 43: 1577 1585. 38. Wells A. Metacognitive Therapy for Anxiety and Depression. The Guilford Press, New York, 2011. 39. Wells A, Fisher P, Myers S, Wheatley J, Patel T, Brewin C. Metacognitive therapy in recurrent and persistent depression: A multiple-baseline study of a new treatment. Cognit. Ther. Res. 2009; 33: 291 300. 40. Watkins ER, Mullan E, Wingrove J et al. Ruminationfocused cognitive-behavioural therapy for residual depression: Phase II randomised controlled trial. Br. J. Psychiatry 2011; 199: 317 322. 41. Russell NJ. Comorbidity in generalized anxiety disorder. Psychiatr. Clin. North Am. 2001; 24: 41 55. 42. Fava M, Rankin MA, Wright EC et al. Anxiety disorders in major depression. Compr. Psychiatry 2000; 41: 97 102. 43. Kessler RC. The epidemiology of pure and comorbid generalized anxiety disorder: A review and evaluation of recent research. Acta Psychiatr. Scand. 2000; 102 (Suppl.): 7 13. 44. Tokuyama M, Nakao K, Seto M, Watanabe A, Takeda M. Predictors of first-onset major depressive episodes among white-collar workers. Psychiatry Clin. Neurosci. 2003; 57: 523 531. 45. Yook K, Kim K-H, Suh SY, Lee KS. Intolerance for uncertainty, worry, and rumination in major depressive disorder and generalized anxiety disorder. J. Anxiety Disord. 2010; 24: 623 628.