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Accepted Manuscript Repetitive negative thinking as a mediator in prospective cross-disorder associations between anxiety and depression disorders and their symptoms Philip Spinhoven, Albert M. van Hemert, Brenda W. Penninx PII:

S0005-7916(18)30101-0

DOI:

https://doi.org/10.1016/j.jbtep.2018.11.007

Reference:

BTEP 1439

To appear in:

Journal of Behavior Therapy and Experimental Psychiatry

Received Date: 11 April 2018 Revised Date:

11 November 2018

Accepted Date: 28 November 2018

Please cite this article as: Spinhoven, P., van Hemert, A.M., Penninx, B.W., Repetitive negative thinking as a mediator in prospective cross-disorder associations between anxiety and depression disorders and their symptoms, Journal of Behavior Therapy and Experimental Psychiatry (2018), doi: https:// doi.org/10.1016/j.jbtep.2018.11.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Repetitive negative thinking as a mediator in prospective cross-disorder associations between anxiety and depression disorders and their symptoms

& Brenda W. Penninx, MD, PhD 3

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Philip Spinhoven, PhD 1,2, Albert M. van Hemert, MD, PhD 2,

Leiden University Medical Center, Department of Psychiatry, Leiden, The Netherlands

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Affiliations: 1 Leiden University, Institute of Psychology, Leiden, The Netherlands

VU University Medical Center, Department of Psychiatry Amsterdam,

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The Netherlands

Corresponding author: Philip Spinhoven, PhD,

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Leiden University, Institute of Psychology, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands. Tel: +31 (0)71 5273377; Fax: +31 (0)71 5274678; E-mail: [email protected]

ACCEPTED MANUSCRIPT Abstract

Background and objectives: Comorbidity among anxiety and depression disorders and their symptoms is high. Rumination and worry have been found to mediate prospective cross-

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disorder relations between anxiety and depression disorders and their symptoms in

adolescents and adults. We examined whether generic repetitive negative thinking (RNT), that is content- and disorder-independent, also mediates prospective cross-disorder

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associations between anxiety and depressions disorders and their symptoms.

Methods: This was studied using a 5-year prospective cohort study. In a mixed sample of

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1,859 adults (persons with a prior history of or a current affective disorder and healthy individuals), we assessed DSM-IV affective disorders (Composite Interview Diagnostic Instrument), anxiety (Beck Anxiety Inventory) and depression symptoms (Inventory of Depressive Symptomatology) and RNT (Perseverative Thinking Questionnaire).

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Results: We found that baseline depression disorders and symptom severity have predictive value for anxiety disorders and symptom severity five years later (and vice versa) and that these associations were significantly mediated by level of RNT as assessed two years after

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baseline. The significant and rather large mediation effects seemed mainly due to the mental

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capacity captured by RNT, especially in the prospective relation of anxiety with future depression.

Limitations: The mediation effects were greatly attenuated or even nullified after rigorously controlling for concomitant psychopathology at two years after baseline. Conclusions: From these results it can be concluded that repetitive negative thinking could be an important transdiagnostic factor, that may constitute a suitable target for treatment.

Key words: anxiety; depression; repetitive negative thinking; longitudinal; mediation

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ACCEPTED MANUSCRIPT 1. Introduction

Anxiety and depression diagnoses tend to co-occur and also their symptoms are highly correlated (Jacobson & Newman, 2017). Several models have been proposed to

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explain the high co-occurrence among mental disorders (Krueger & Markon, 2006). The liability spectrum model assumes that psychopathology, rather than consisting of a multitude of discrete disorders, is more likely to reflect as a smaller number of broad

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dimensions (Kotov, et al., 2017). These underlying dimensions are also referred to as

transdiagnostic risk factors (e.g. Harvey, Watkins, Mansell, & Shafran, 2004). Repetitive

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negative thinking (RNT: Ehring & Watkins, 2008) in the form of rumination and worry is one of the main candidate cognitive transdiagnostic risk factors for comorbidity among anxiety and depression. Rumination and worry share many similarities, including the characteristics that they are repetitive, difficult to control, negative in content, predominantly

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verbal, and relatively abstract (Watkins, 2008).

The study of RNT is complicated by the fact that most measures relate either to rumination or worry, the assessment of which include content-specific or disorder-specific

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items (McEvoy, Watson, Watkins, & Nathan, 2013; Samtani & Moulds, 2017). To allow studies of content- and disorder-independent RNT, two generic RNT measures have been

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developed and validated: the Repetitive Thinking Questionnaire (RTQ; Mahoney, McEvoy, & Moulds, 2012; McEvoy, Mahoney, & Moulds, 2010; McEvoy, Thibodeau, & Asmundson, 2014) and the Perseverative Thinking Questionnaire (PTQ; Ehring, Raes, Weidacker, & Emmelkamp, 2012; Ehring, et al., 2011). Cross-sectional studies with the RTQ and PTQ in non-clinical (Ehring, et al., 2012; Ehring, et al., 2011; McEvoy, et al., 2010) and clinical (Ehring, et al., 2011; Mahoney, et al., 2012; Samtani, et al., 2018) samples showed that these disorder-independent measures of RNT are strongly associated with severity of depression, anxiety and general distress. In addition, it has been found that PTQ scores prospectively

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ACCEPTED MANUSCRIPT predict severity of depression symptoms in a non-clinical sample (Topper, Molenaar, Emmelkamp, & Ehring, 2014), also after controlling for baseline severity (Raes, 2012). In a pivotal prospective study McLaughlin and Nolen-Hoeksema (2011) found that baseline depression symptoms predicted subsequent increases in anxiety symptoms and

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rumination fully mediated this association. In line, baseline disorders (social anxiety

disorder, panic disorder and agoraphobia) have been found to predict subsequent changes in distress disorders (depressive disorder, dysthymia and Generalized Anxiety Disorder) (and

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vice versa) and changes in worry and rumination (partly) mediated these associations (Drost, van der Does, van Hemert, Penninx, & Spinhoven, 2014).

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We are not aware of studies examining generic RNT as a mediator in the prospective relationship of depression with anxiety (and vice versa). Conceptually replicating the above prospective associations of anxiety and depression with a generic RNT measure would contribute to evidence for the view that in particular content-independent dimensions of RNT

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(such as repetitiveness, intrusiveness, or difficulties with disengagement) are relevant in these associations. Consequently, the aim of the present 5-year longitudinal study is to examine to what extent dimensions of RNT mediate the prospective association of depression with

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anxiety and vice versa. We hypothesized that content-independent RNT would mediate both

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the longitudinal association of anxiety with subsequent depression and of depression with subsequent anxiety. We did not have specific predictions about which dimensions of RNT would be most influential in these relationships.

2. Material and methods 2.1. Participants and design The NESDA study is an ongoing cohort study designed to investigate determinants, course and consequences of depression and anxiety disorders. A sample of 2981 persons aged

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ACCEPTED MANUSCRIPT 18 to 65 years was included, consisting of healthy controls, persons with a prior history of depression and/or anxiety disorders, and persons with a current depression and/or anxiety disorder. Respondents were recruited in the general population, through a screening procedure in general practice, or when newly enrolled in specialized health care in order to different

health

care

settings

and

different

developmental

stages

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represent

of

psychopathology. General exclusion criteria were a primary diagnosis of severe psychiatric disorders such as psychotic, obsessive compulsive, bipolar or severe addiction disorder, and

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not being fluent in Dutch. A detailed description of the NESDA design and sampling procedures has been given elsewhere (Penninx, et al., 2008). The research protocol was

provided written informed consent.

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approved by the Ethical Committees of the participating universities and all respondents

The baseline assessment included demographic and personal characteristics, a standardized diagnostic psychiatric interview and a medical assessment including blood

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sampling. After two (T2), four (T4), six years (T6), and nine years (T9) a face-to-face followup assessment was conducted with a response of 87.1% (n=2596) at T2, 80.6 % (n=2402) at T4, 75.7 % (n = 2256) at T6, and 69.4% (n=2069) at T9. As within the NESDA study the

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PTQ was administered for the first time at T6, we selected all participants at T4 with

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complete T6 PTQ data and complete T9 CIDI data (n = 1859).

2.2. Measures

Psychiatric diagnoses. The diagnostic status (6-month prevalence) of depression

[Major Depressive Disorder (MDD), Dysthymia (DYS)] or anxiety [Panic Disorder with or without Agoraphobia (PD), Social Anxiety Disorder (SAD), Generalized Anxiety Disorder (GAD), Agoraphobia without panic (AGO)] disorders according to DSM-IV criteria (APA,

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ACCEPTED MANUSCRIPT 1994) was established at T4, T6 and T9 using the Composite Interview Diagnostic Instrument (CIDI-WHO lifetime version 2.1) (Wittchen, 1994). Symptom severity. Severity of depression symptoms was measured using the 30item Inventory of Depressive Symptomatology (IDS; Rush, et al., 1986; Rush, Gullion,

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Basco, Jarrett, & Trivedi, 1996). Severity of anxiety symptoms was measured using the 21item Beck Anxiety Inventory (BAI; Beck, Brown, Epstein, & Steer, 1988; Osman, et al., 2002).

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Perseverative thinking. Perseverative thinking was measured with the 15-item Perseverative Thinking Questionnaire (PTQ; Ehring, et al., 2012; Ehring, et al., 2011).

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Participants are asked to rate on a scale from ‘0’ (never) to ‘4’ (almost always) how often each of the items applies to their process of thinking. The item pool comprises three items for each of the assumed process characteristics of repetitive negative thinking: (1) repetitiveness, (2) intrusiveness, (3) difficulty to disengage from, as well as (4) unproductiveness, and (5)

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capturing mental capacity. Based on previous confirmatory factor-analyses (CFA) (Ehring, et al., 2012; Ehring, et al., 2011) three subscales were calculated called ‘core characteristics of RNT’ (i.e., repetitiveness, intrusiveness, difficulties with disengagement) (9 items),

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‘perceived unproductiveness of RNT’ (3 items), and ‘RNT capturing mental capacity’ (3

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items). In the present study, CFA using WLSMV parameter estimates in Mplus (version 7.0) (Muthén & Muthén, 1998-2012) showed that such a model showed an adequate fit to the data (CFI=.95; TLI=.94; RMSEA=.081 (95% CI: .078 - .084)).

2.3. Statistical analyses We examined ten multiple mediation models in which the longitudinal association of depression with anxiety (and vice versa) was mediated by subscale scores for repetitive negative thinking (see Fig. 1) using the Process macro of Hayes (Preacher & Hayes, 2008).

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ACCEPTED MANUSCRIPT More specifically, we analyzed: 1) four models for the indirect association of T4 mood disorders (MDD and/or DYS) with each of the T9 anxiety disorders (i.e. GAD, SAD, PD, or AGO) using logistic regression analyses; 2) four models for the indirect association of each of the T4 anxiety disorders with T9 mood disorders through T6 PTQ subscale scores,

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controlling for corresponding T4 depression or anxiety disorders using logistic regression analyses; and two models for the indirect association of T4 depression symptom severity with T9 anxiety symptom severity (and vice versa) through T6 PTQ scores controlling for

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corresponding T4 symptom severity scores using multiple regression analyses. Each of these 10 analyses was repeated by including psychiatric diagnoses (i.e., mood disorder, GAD,

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SAD, PD, and AGO) at T6 as control variables in the first eight models and both IDS and BAI scores at T6 as control variables in the last two models. The significance of the indirect effect through PTQ subscale scores was determined using a bootstrap approximation with 5000 iterations to obtain biased-controlled confidence intervals. The magnitude of the

3. Results

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3.1. Descriptive statistics

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indirect effect is presented by standardized beta weights.

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Study dropouts (n = 543; 22.6%) between T4 and T9 more often had mood disorder, GAD, SAD, PD or AGO, manifested higher levels of anxiety (BAI) and depression (IDS), and had a lower level of education at T4. The size of the differences was negligible except for small differences in years of education and level of anxiety (see supplementary material). Demographic and clinical characteristics of our final sample with complete PTQ T6 and T9 follow-up data are presented in Table 1.

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ACCEPTED MANUSCRIPT 3.2. Mediation analysis Results showed that mood disorders at T4 had a significant direct effect on each of the T9 anxiety disorders (.69 < β < .85; .05 > p > .01) and that each of the T4 anxiety disorders (except AGO) had a significant direct effect on T9 mood disorders (.53 < β < .71; .05 > p >

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.001) (see Table 2). None of these effects remained significant after including T6 PTQ subscale scores into the mediation model, while the total indirect effects of T4 mood

disorders on each of the T9 anxiety disorders through T6 PTQ subscale scores (.37 < estimate

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< .60, all p < .001) and the total indirect effect of each of the T4 anxiety disorders on T9

mood disorders through T6 PTQ subscale scores (.28 < estimate < .44; .01 > p > .001) were

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all statistically significant. The proportion mediated was rather large ranging from .51 to .80 in predicting T9 anxiety disorders and from .50 to .64 in predicting T9 mood disorders. Of note is that in predicting T9 mood disorders by T4 anxiety disorders, T6 subscale scores for capturing mental capacity were the only significant unique mediator in each

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analysis (.14 < estimate < .23; all p < .05). Only in the prediction of T9 SAD by T4 mood disorders, significant unique mediators were identified: capturing mental capacity (estimate = .33; p < .05) and unproductivity (estimate = .25; p < .05).

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In predicting T9 BAI anxiety severity scores by T4 IDS depression severity scores

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(and vice versa) comparable results were found, although the direct effect of anxiety severity on depression severity (β = .14, p < .001) (and vice versa) (β = .06, p < .05) remained statistically significant after including T6 PTQ subscale scores into the mediation model. In both analyses the total indirect effect was significant (estimate = .03 in predicting anxiety severity and .06 in predicting depression severity; all p < .001). In predicting T9 depression severity, capturing mental capacity was the only significant unique mediator (estimate = .02; p < .01) and in predicting T9 anxiety severity both capturing mental capacity (estimate = .03; p < .05) and core characteristics of repetitive negative thinking (estimate = .03; p < .05)

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ACCEPTED MANUSCRIPT proved to be significant unique mediators. Effect sizes for the total indirect effect of symptom severity were smaller than in predicting disorders: .48 in predicting anxiety severity and .19 in predicting depression severity.

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The associations of RNT dimensions with concomitant symptom severity were high (>.50), with mood disorders moderate (>.30) and with anxiety disorders small (>.10) (see supplementary material). Repeating the analyses above statistically controlling for presence

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of psychiatric disorders or symptom severity at T6 greatly reduced the direct predictive effect of psychopathology variables at T4 and attenuated and even nullified the mediation effect of

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PTQ scores at T6 in five of the ten analyses. Although in analyzing psychiatric disorders the total indirect effects remained significant in five of the eight analyses, only in predicting mood disorders by SAD at T4 a significant unique mediating effect of capturing mental capacity remained present (see table 2).

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4. Discussion

Our research aim was to assess to what extent dimensions of RNT mediate the longitudinal association of depression with anxiety (and vice versa). The results of our

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mediation analyses consistently show that the predictive value of depression disorders and

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severity of depression symptoms for future anxiety disorders, respectively severity of anxiety symptoms (and vice versa) is significantly mediated by RNT. This significant and rather large mediation effect seems mainly due to the mental capacity captured by RNT, especially in the prospective relation of anxiety with future depression. These results confirm previous studies showing that disorder- and content-dependent rumination or worry mediate the prospective relationship of anxiety with depression (and vice versa) (Drost, et al., 2014; McLaughlin & Nolen-Hoeksema, 2011). The present study extends these findings by demonstrating that disorder- and content-independent RNT also

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ACCEPTED MANUSCRIPT mediates these relations and that the results of previous studies are not entirely due to the putative biased way of measuring RNT in the form of rumination or worry. Interestingly, the core characteristics of the actual repetitive negative thinking process (i.e., the thinking is repetitive, it is at least partly intrusive, and it is difficult to disengage from) as measured by

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the NRT factor of the PTQ (Ehring, et al., 2011) proved to be less crucial in mediating the cross-disorder associations of anxiety with depression. In particular the perceived dysfunctional effects of RNT in the form of capturing mental capacity showed an

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independent unique contribution in most of the mediation analyses. Capturing mental

capacity is measured with the following items of the PTQ: "I can’t do anything else while

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thinking about my problems", "My thought prevent me from focusing on other things", and "My thoughts take up all my attention". Capturing of mental capacity may reflect impairments in attention and memory due to difficulties in expelling irrelevant or no longer relevant negative information from working memory. This interpretation is in line with recent

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experimental studies showing that individuals with high rumination scores are characterized by impaired inhibition and switching in working memory when negative information is in focal attention (Ansari, Derakshan, & Richards, 2008; Joormann & Gotlib, 2008). Moreover,

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previous studies have also observed overall reduced working memory capacity in anxiety and

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depression (Moran, 2016; Rose & Ebmeier, 2006) and both disorders are characterized by reduced levels of frontal activity (Bishop, Duncan, Brett, & Lawrence, 2004; Levin, Heller, Mohanty, Herrington, & Miller, 2007). However, it should be noted that after controlling for presence of psychiatric disorders

or symptom severity at T6, the direct predictive effect of psychopathology was greatly reduced and the total mediation effect of RNT was no longer significant in predicting mood disorder by PD and AGO and AGO by mood disorder and even nullified in analyzing symptom severity. Moreover, after this correction capturing mental capacity only remained a

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ACCEPTED MANUSCRIPT unique mediating variable in predicting mood disorder by SAD. A statistical reason for this 'shrinking' effect could be that RNT is so intrinsically associated with presence or severity of depression and anxiety that by statistically controlling for these variables, the statistical power of RNT to uniquely predict depression or anxiety is greatly reduced if not eliminated.

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Moreover, several symptoms tapped by measures for symptom severity (such as

dysfunctional thinking) may not only index symptom severity, but also play a causal role in the onset and maintenance of disorders according to network models of psychopathology

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(Borsboom and Cramer, 2013).

Our study also has a few limitations that should be kept in mind when interpreting the

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results. As there is no gold standard to assess the size of the indirect effect across different statistical models for multiple mediation, proportion mediated as effect sizes in the present study only gives a global indication and is difficult to interpret in an absolute way. A second limitation concerns the limited number of mental disorders assessed in the present study.

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Disorders such as PTSD and OCD were not represented, neither were other disorders known for elevated levels of RNT such as pain disorders or hypochondriasis. Moreover, selective attrition although minimal may limit generalizability of the present study results.

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Overall, the findings from the present study suggest that disorder- and content-

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independent RNT may constitute an important transdiagnostic factor responsible for the cooccurrence of anxiety and depression disorders and their symptom severity. Given the intricate association of RNT with psychopathology, mediation studies are needed in order to test whether including interventions specifically targeting RNT has benefit in the transdiagnostic treatment of depression and anxiety.

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ACCEPTED MANUSCRIPT Figure legend

Figure 1. Multiple mediation model of prospective cross-disorder relationships through

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dimensions of repetitive negative thinking

Note. Anx = Anxiety disorder or anxiety symptom severity; Dep = Depression disorder or depression symptom severity; RNT = core characteristics of RNT (i.e., repetitiveness,

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intrusiveness, difficulties with disengagement); Unp = perceived unproductiveness of RNT;

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MC = RNT capturing mental capacity.

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Table 1. Demographic and clinical characteristics (N = 1,859) ACCEPTED MANUSCRIPT Variables T4 T9 N % N % Demographic characteristics Age (M/SD) 46.0 13.2 Gender (Female) 1229 66.1 Education (M/SD) 13.0 3.3 Self-reports IDS (M/SD) 14.8 11.7 14.5 11.4 BAI (M/SD) 7.6 8.1 7.4 8.2 PTQ at T6 Core characteristics (M/SD) 2.5 0.9 Perceived unproductiveness (M/SD) 2.3 1.0 Capturing mental capacity (M/SD) 2.0 0.9 Psychiatric diagnosis Any disorder 542 29.2 491 26.4 MD 322 17.3 286 15.4 GAD 104 5.6 77 4.1 SAD 184 9.9 159 8.6 PD 131 7.0 132 7.1 AGO 76 4.1 87 4.7 MD + GAD 66 / 322 20.5 48 / 286 16.8 MD + SAD 83 / 322 25.8 71 / 286 24.8 MD + PD 60 / 322 18.6 60 / 286 21.0 MD + AGO 27 / 322 8.4 28 / 286 9.8 GAD + MD 66 / 104 63.5 48 / 77 62.3 SAD + MD 83 / 184 45.1 71 / 159 44.7 PD + MD 60 / 131 45.8 60 / 132 45.5 AGO + MD 27 / 76 35.5 28 / 87 32.2 Note. M = mean; SD = standard deviation; IDS = Inventory of Depressive Symptomatology; BAI = Beck Anxiety Inventory; PTQ = Perseverative Thinking Questionnaire; MDD = Major Depressive Disorder; Dys = Dysthymia; GAD = Generalized Anxiety Disorder; SAD = Social Anxiety Disorder; PD = Panic Disorder; Ago = Agoraphobia; MD = Mood Disorder (i.e., MDD and/or DYS)

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Table 2. PTQ scores at T6 as mediators of the effect of T4 predictors on T9 outcomes correcting for corresponding T4 baseline values

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PTQ scores while controlling for concurrent psychopathology Total Direct Total Unique Effect effect effect indirect indirect size effect effect mediation (1-c’/c) (c) (c’) (Σ a x b) (a x b) .235 .077 .198 *** .672 -.015 .050 .163 ** .171 .009 .188 * .995 .024 .060 .105 .448 .292 .166** .349 .049 .090 .026 .228 .134 .082 .412 .024 -.033 .092 .183 .073 .164 *** .601 .080 -.012 .098 .193 .084 .128 ** .565 .069 -.012 .071

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MD to SAD x RNT x Unp x MC MD to GAD x RNT x Unp x MC MD to PD x RNT x Unp x MC MD to AGO x RNT x Unp x MC SAD to MD x RNT x Unp x MC GAD to MD x RNT x Unp x MC

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Mediator

PTQ scores without control for concurrent psychopathology Total Direct Total Unique Effect effect effect indirect indirect size effect effect mediation (c) (c’) (1-c’/c) (Σ a x b) (a x b) .599 ** .146 .572 *** .756 -.003 .247 * .327 * .669 * .151 .597 *** .734 .089 .275 .232 .606 ** .265 .427 *** .563 .126 .235 .067 .696 ** .346 .367 *** .503 .034 .069 .261 .626 ** .272 .438 *** .566 .138 .073 .227 * .601 * .268 .409 *** .554 .131 .072 .206 *

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na

.424

.800

.036

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PD to MD .451 * .193 .342 *** .572 -.097 -.128 .073 x RNT .114 .042 x Unp .054 -.001 x MC .173 ** .032 AGO to MD .516 .278 .280 ** .461 .132 .076 .097 x RNT .094 .053 x Unp .045 -.005 x MC .141 * .050 IDS to BAI a .123 *** .064 * .059 *** .480 .005 .001 .004 x RNT .033 * .007 x Unp -.003 -.004 x MC .029 * .001 BAI to IDS b .173 *** .140 *** .033 *** .191 .083** .080 ** .003 x RNT .008 .001 x Unp .005 .000 x MC .021 ** .002 Note. MD = mood disorder (Major Depressive Disorder and/or Dysthymia); SAD = Social Anxiety Disorder; GAD = Generalized Anxiety Disorder; PD = Panic Disorder with or without agoraphobia; AGO = Agoraphobia without panic; Unp = perceived unproductiveness of RNT; MC = RNT capturing mental capacity; RNT = core characteristics of RNT (i.e., repetitiveness, n = 1769 because of missing data; b = 1764 because of missing data; * p <.05; ** p<.01; *** p <.001

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a

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intrusiveness, difficulties with disengagement);

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ACCEPTED MANUSCRIPT Penninx, B. W., Beekman, A. T., Smit, J. H., Zitman, F. G., Nolen, W. A., Spinhoven, P., Cuijpers, P., De Jong, P. J., Van Marwijk, H. W., Assendelft, W. J., Van Der Meer, K., Verhaak, P., Wensing, M., De Graaf, R., Hoogendijk, W. J., Ormel, J., & Van Dyck, R. (2008). The Netherlands Study of Depression and Anxiety (NESDA):

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ACCEPTED MANUSCRIPT Samtani, S., & Moulds, M. L. (2017). Assessing maladaptive repetitive thought in clinical disorders: a critical review of existing measures. Clinical Psychology Review, 53, 1428. Topper, M., Molenaar, D., Emmelkamp, P. M. G., & Ehring, T. (2014). Are rumination and

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57-84.

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ACCEPTED MANUSCRIPT Highlights

* Baseline depression disorder and severity predicted anxiety five years later * Baseline anxiety disorder and severity predicted depression five years later

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* Associations were mediated by level of repetitive negative thinking (RNT)

* Mediation effects seemed mainly due to the mental capacity captured by RNT

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* Mediation effects were attenuated by controlling for concomitant psychopathology

ACCEPTED MANUSCRIPT Conflict of interest All authors declare that they have no conflicts of interest.

Acknowledgement

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The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and

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mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical

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Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). This article was written while prof. Philip Spinhoven, was a Fellow at the Netherlands Institute of Advanced Studies (NIAS) as part of the theme group "My

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optimism wears heavy boots".

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