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Repetitive negative thinking and intolerance of uncertainty are risk and maintenance factors for emotional disorders. Although emerging evidence suggests that intolerance of uncertainty predicts increases in distress through repetitive negative thinking, these relationships have yet to be investigated among veterans. The present study examines if repetitive negative thinking mediates the relationships of intolerance of uncertainty with stress, disordered symptoms and impairment among a mixed clinical sample of veterans. Two hundred and forty-four treatment-seeking veterans with diagnoses of major depressive disorder, panic disorder, or posttraumatic stress disorder completed measures of intolerance of uncertainty, repetitive negative thinking, stress, impairment, depression, panic, and posttraumatic stress prior to receiving treatment. Mediation models revealed indirect effects of intolerance of uncertainty through repetitive negative thinking on stress and impairment in the full sample, and on disordered symptoms in subsamples with major depressive disorder and posttraumatic stress disorder. Conversely, intolerance of uncertainty did not have direct or indirect effects on disordered symptoms in a panic disorder subsample. Findings suggest that repetitive negative thinking and intolerance of uncertainty uniquely contribute to stress, impairment, and disordered symptoms, but repetitive negative thinking, may, in part, drive intolerance of uncertainty's contribution to emotional disorders. Interventions for repetitive negative thinking might improve the efficacy of existing transdiagnostic treatment protocols. Cross-sectional data is a limitation of the present study. Prospective designs in civilian samples can better establish the temporality of these relationships and if they are generalizable to the larger population.

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BACKGROUND: Repetitive negative thinking (RNT) is a transdiagnostic process involving perseverative, unproductive, and uncontrollable thoughts. Although RNT may impede adaptive psychosocial functioning by prolonging negative mood states, strengthening cognitive biases, and preventing effective problem-solving, the extent to which RNT is associated with risk for poor psychosocial outcomes is unclear. Given that this has clear transdiagnostic treatment implications, the present study aimed to isolate the unique relationship of RNT with social functioning and life satisfaction in a mixed clinical and non-clinical sample. METHODS: In 201 mid-to-later life adult participants (27 with primary diagnoses of bipolar disorder, 84 with major depressive disorder, and 90 healthy volunteers), we measured RNT, social functioning, life satisfaction, trait rumination, DSM-5 diagnoses, depressive symptoms, manic symptoms, cognitive control performance, and global cognitive functioning. RESULTS: Linear regression models revealed that RNT, but not rumination, was significantly associated with poorer social functioning (ß = 0.42 p < .001) and reduced life satisfaction (ß = -0.42, p < .001) after controlling for clinical and cognitive covariates. LIMITATIONS: Limited demographic diversity, cross-sectional design, self-reporting of outcomes. CONCLUSIONS: Results suggest that RNT may confer risk for key psychosocial outcomes during middle to later adulthood, over and above the effects of clinical and cognitive variables and independent of diagnostic status. Findings lend support to the notion of RNT as a transdiagnostic process and suggest that RNT may be an important therapeutic target for adults with poor social functioning and/or reduced life satisfaction.

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BACKGROUND: Delivery of preventative interventions via mobile phone apps offers an effective and accessible way to address the global priority of improving the mental health of adolescents and young adults. A proven risk factor for anxiety and depression is elevated worry and rumination, also known as repetitive negative thinking (RNT). OBJECTIVE: This was a prevention mechanism trial that aimed to investigate whether an RNT-targeting self-help mobile phone app (MyMoodCoach) reduces worry and rumination in young adults residing in the United Kingdom. A secondary objective was to test whether the app reduces symptoms of anxiety and depression and improves well-being. METHODS: A web-based, single-blind, 2-arm parallel-group randomized controlled trial was conducted with 236 people aged between 16 and 24 years, who self-reported high levels of worry or rumination. Eligible participants were randomized to an active intervention group (usual practice, plus up to 6 weeks of using the RNT-targeting mobile app, n=119) or a waitlist control group (usual practice with no access to the app until after 6 weeks, n=117). The primary outcome was changes in worry and rumination 6 weeks after randomization. Secondary outcomes included changes in well-being and symptoms of anxiety and depression after 6 weeks and changes in all measures after 12 weeks. RESULTS: Participants randomly allocated to use the RNT-targeting self-help app showed significantly lower levels of rumination (mean difference -2.92, 95% CI -5.57 to -0.28; P=.03; ηp2=0.02) and worry (mean difference -3.97, 95% CI -6.21 to -1.73; P<.001; ηp2=0.06) at 6-week follow-up, relative to the waitlist control. Similar differences were observed for well-being (P<.001), anxiety (P=.03), and depression (P=.04). The waitlist control group also showed improvement when given access to the app after 6 weeks. Improvements observed in the intervention group after 6 weeks of using the app were maintained at the 12-week follow-up point. CONCLUSIONS: The MyMoodCoach app had a significant positive effect on worry and rumination, well-being, anxiety, and depression in young adults, relative to waitlist controls, providing proof-of-principle that an unguided self-help app can effectively reduce RNT. This app, therefore, has potential for the prevention of anxiety and depression although longer-term effects on incidence need to be directly evaluated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04950257; https://www.clinicaltrials.gov/ct2/show/NCT04950257. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-021-03536-0.

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Introduction: Individuals with subjective cognitive decline (SCD) express concern about self-perceived cognitive decline despite no objective impairment and are at higher risk of developing Alzheimer's disease. Despite documented links between SCD and repetitive negative thinking (RNT), the specific impact of RNT on brain integrity and cognition in exacerbating the SCD condition remains unclear. We aimed to investigate the influence of RNT on global cognition and brain integrity, and their interrelationships among healthy middle-aged and older adults experiencing SCD. Methods: Out of 616 individuals with neuroimaging and neuropsychological data available, 89 (mean age = 56.18 years; 68.54% females) met SCD criteria. Eighty-nine non-SCD individuals matched by age, sex, and education were also selected and represented the control group (mean age = 56.09 years; 68.54% females). Global cognition was measured using the preclinical Alzheimer's cognitive composite (PACC5), which includes dementia screening, episodic memory, processing speed, and category fluency tests. RNT was calculated through three questionnaires assessing intrusive thoughts, persistent worry, and rumination. We generated cortical thickness (CTh) maps and quantified the volume of white matter lesions (WML) in the whole brain, as grey and white matter integrity measures, respectively. Results: SCD individuals exhibited higher RNT scores, and thinner right temporal cortex compared to controls. No differences were observed in PACC5 and WML burden between groups. Only the SCD group demonstrated positive associations in the CTh-PACC5, CTh-RNT, and WML-RNT relationships. Discussion: In this cross-sectional study, RNT was exclusively associated with brain integrity in SCD. Even though our findings align with the broader importance of investigating treatable psychological factors in SCD, further research may reveal a modulatory effect of RNT on the relationship between cognition and brain integrity in SCD.

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Exposure to nature can enhance mental well-being, making nature-based interventions promising for the treatment and prevention of mental health problems like depression. Given the decreased self-focus and sense of self-diminishment associated with awe, the present study investigated the impact of exposure to awe-evoking nature on two key risk and maintenance factors of depression-repetitive negative thinking (RNT) and dampening of positive feelings-and on subjective happiness. In a randomized controlled trial, we tested the effects of exposure to awe-evoking nature clips through a 1-week intervention, consisting of watching a 1-min clip on a daily basis of either awe-evoking (n high awe = 108) or more mundane nature scenes (n low awe = 105). Before, immediately after (post-intervention) and 1 week after the intervention (follow-up), participants completed self-report scales probing RNT, dampening, and subjective happiness. Results indicated significant decreases in these outcomes at post-intervention and follow-up in both groups. We discuss study limitations, touch upon future research ideas, and reflect upon the role of nature for clinical applications.

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Repetitive negative thinking (RNT) is a transdiagnostic construct that encompasses rumination and worry, yet what precisely is shared between rumination and worry is unclear. To clarify this, we develop a meta-control account of RNT. Meta-control refers to the reinforcement and control of mental behavior via similar computations as reinforce and control motor behavior. We propose rumination and worry are coarse terms for failure in meta-control, just as tripping and falling are coarse terms for failure in motor control. We delineate four meta-control stages and risk factors increasing the chance of failure at each, including open-ended thoughts (stage 1), individual differences influencing subgoal execution (stage 2) and switching (stage 3), and challenges inherent to learning adaptive mental behavior (stage 4). Distinguishing these stages therefore elucidates diverse processes that lead to the same behavior of excessive RNT. Our account also subsumes prominent clinical accounts of RNT into a computational cognitive neuroscience framework.

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Insomnia symptoms are highly prevalent during pregnancy; therefore, identifying modifiable risk markers is important for risk prediction and early intervention. This study aimed to examine the role of sleep-specific rumination and sleep-specific worry in prenatal insomnia symptoms. A total of 859 married pregnant women without history of psychiatric illnesses (mean [standard deviation] age, 30.15 [3.86] years; 593 [69.0%] with a bachelor's degree or above) were enrolled from the obstetrical outpatient departments of two tertiary comprehensive hospitals in Shandong, China, who completed assessments of sleep-specific rumination, sleep-specific worry, and insomnia symptoms at baseline (mid-pregnancy) and follow-up (late-pregnancy). Measures included Daytime Insomnia Symptom Response Scale, Anxiety and Preoccupation about Sleep Questionnaire, and Insomnia Severity Index. Our results showed that after controlling for covariates, both sleep-specific rumination and sleep-specific worry showed significant concurrent and prospective associations with insomnia symptoms, and the increases in scores of sleep-specific rumination and sleep-specific worry over time were significantly associated with the increased likelihood of insomnia symptoms at follow-up. Moreover, the increases in sleep-specific rumination and sleep-specific worry over time were significantly associated with the increased likelihood of reporting newly developed insomnia symptoms rather than persistent normal sleep. However, the changes in sleep-specific rumination and sleep-specific worry were not significantly associated with the likelihood of reporting persistent or remitted insomnia symptoms rather than persistent normal sleep. In conclusion, sleep-specific rumination and sleep-specific worry were significantly associated with concurrent or subsequent insomnia symptoms; thus, they may be promising cognitive risk markers and intervention targets.

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Introduction: Mental health conditions are associated with cognition and physical function in older adults. We examined whether worry and ruminative brooding, key symptoms of certain mental health conditions, are related to subjective and/or objective measures of cognitive and physical (cardiovascular) health. Methods: We used baseline data from 282 participants from the SCD-Well and Age-Well trials (178 female; agemean = 71.1 years). We measured worry and ruminative brooding using the Penn State Worry Questionnaire and the Ruminative Response Scale-brooding subscale. We assessed subjective physical health using the WHOQOL-Bref physical subscale, and objective physical health via blood pressure and modified versions of the Framingham Risk Score and Charlson Comorbidity Index. With subjective and objective cognition, we utilized the Cognitive Difficulties Scale and a global composite (modified Preclinical Alzheimer's Cognitive Composite, PACC5, with the Wechsler Adult Intelligence Scale-IV, category fluency, Mattis Dementia Rating Scale-2, and either the California Verbal Learning Test or the Rey Auditory Verbal Learning Test). We conducted linear regressions, adjusted for education, age, sex and cohort. Results: Worry and ruminative brooding were negatively associated with subjective physical health (worry: ß = -0.245, 95%CI -0.357 to -0.133, p < 0.001; ruminative brooding: ß = -0.224, 95%CI -0.334 to -0.113, p < 0.001) and subjective cognitive difficulties (worry: ß = 0.196, 95%CI 0.091 to 0.302, p < 0.001; ruminative brooding: ß = 0.239, 95%CI 0.133 to 0.346, p < 0.001). We did not observe associations between worry or ruminative brooding and any measure of objective health. Discussion: Worry and ruminative brooding may be common mechanisms associated with subjective but not objective health. Alternatively, cognitively unimpaired older adults may become aware of subtle changes not captured by objective measures used in this study. Interventions reducing worry and ruminative brooding may promote subjective physical and cognitive health; however, more research is needed to determine causality of the relationships.

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BACKGROUND: Repetitive negative thinking (RNT) symptoms, which are characterized by pervasive, uncontrollable negative thoughts, are common in individuals with mood, anxiety, and traumatic stress disorders. Inability to regulate the contents of working memory is a hypothesized etiological factor in RNT, which suggests that training to improve working memory may be beneficial. This study examined the effects of working memory training on resting-state functional connectivity (rsFC) in individuals with elevated RNT and whether such changes would be associated with clinical improvement. METHODS: We conducted a secondary analysis of pre-post resting-state data collected as part of a randomized controlled trial (NCT04912089) of working memory training interventions (n = 42) compared with a waitlist control group (n = 23). We hypothesized that individuals who completed training would show increased rsFC between the 2 key intrinsic connectivity networks-the default mode network (posterior cingulate cortex) and the frontoparietal network (dorsolateral prefrontal cortex). We explored whether the magnitude of rsFC change was associated with change in RNT symptom severity. RESULTS: rsFC increased between the posterior cingulate cortex and regions including the frontal and parietal cortex in the training group compared with the waitlist group. Increased connectivity between the posterior cingulate cortex and superior frontal cortex was associated with RNT symptom reduction. CONCLUSIONS: These data provide evidence that working memory training can modulate neural circuitry at rest in individuals with RNT. Results are consistent with accounts of working memory training effects on large-scale neurocircuitry changes and suggest that these changes may contribute to clinical promise of this type of intervention on transdiagnostic RNT symptoms.

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People high in depressive or anxious symptom severity show repetitive negative thinking, including worry and rumination. They also show various cognitive phenomena, including probability, cost, and interpretation biases. Since there is conceptual overlap between these cognitive biases and repetitive negative thinking - all involve thinking about potential threats and misfortunes - we wondered whether repetitive negative thinking could account for (mediate) these cognitive biases' associations with depressive and anxious symptom severity. In three studies, conducted in two languages and cultures, cost bias and (in two studies) interpretation bias only predicted symptom severity via worry and repetitive negative thinking; this suggests these biases are actually associated with repetitive negative thinking, rather than with symptoms. In contrast, probability bias showed direct relationships with depressive (all studies) and anxious (two studies) symptom severity, suggesting its relationships with symptoms are partly independent of repetitive negative thinking. These results show the value of studying relationships among the various cognitive features of psychopathology. Furthermore, new interventions which target cognitive biases in depression or anxiety must show that they can improve upon cognitive behavioural therapy, which is already widely available, targets both repetitive negative thinking and probability bias, and is highly effective.

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Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.

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Background: Immediate reward preference in repetitive negative thinking (RNT) has a high clinical correlation with a variety of maladaptive behaviors, whereas episodic future thinking (EFT) may be conducive to dealing with non-adaptive thinking and decision-making. Objectives: This study aimed to evaluate the efficacy of EFT training combined with transcranial direct current stimulation (tDCS) stimulation over the ventromedial PFC (vmPFC) in inhibiting impulsive choice of RNT individuals. Method: Study 1 explored the effects of EFT on immediate reward preference of participants with high and low RNT (N = 48). Study 2 conducted a randomized controlled trial (RCT) to examine the treatment effect of the EFT-neural training on impulsive choice of high RNT individuals (N = 103). Results: In study 1, individuals with high RNT were more likely to choose smaller and sooner (SS) rewards, however, there were no significant differences between the high-RNT group and the low-RNT group under the positive EFT condition. In study 2, a significant decrease was shown in the proportion of choosing SS rewards under the 8-week EFT-neural training, and the effect was maintained at 1 month follow-up. Conclusion: RNT is a vulnerability factor for short-sighted behaviors, and EFT-neural training could be suitable for reducing RNT and improving immediate reward preference.

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Prior research suggests that repetitive negative thinking (RNT) negatively impacts mental health by intensifying and prolonging emotional reactivity to stress. This study investigated whether an intervention designed to reduce RNT alters emotional reactivity. Young adults with high trait RNT (N = 79) were randomly allocated to an RNT-focused intervention (smartphone app-based, 10 days) or a waiting list before exposure to a standardized stressor. The pre-registered analysis did not reveal a significant condition * time interaction for negative affect. However, exploratory analyses showed that whilst initial increases in negative affect in response to the stressor did not differ between conditions, participants in the intervention condition reported less negative affect throughout the following recovery phase. Additionally, participants in the intervention condition appraised their ability to cope with the stressor as higher and reported less RNT in the recovery phase. In contrast, the intervention did not affect biological stress responses. The findings indicate that RNT-focused interventions might have positive effects on mental health by breaking the self-reinforcing cycle of RNT, negative affect and maladaptive appraisals in response to stress. However, as findings are partly based on exploratory analyses, further research is needed to confirm whether reduced subjective stress reactivity mediates the effects of RNT-focused interventions on psychopathological symptoms.

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BACKGROUND: Posttraumatic stress disorder (PTSD) and sleep disturbance are highly comorbid and repetitive negative thinking (RNT) is associated with both sleep disturbance and PTSD. However, few studies have examined the association between RNT and sleep disturbance in individuals exposed to trauma, with and without PTSD. METHOD: Associations between trait-level and trauma-related RNT, insomnia, and sleep quality were investigated in a trauma-exposed MTurk (N = 342) sample. Additionally, PTSD symptom severity was tested as a moderator of the associations between RNT and insomnia and sleep quality. RESULTS: Trait-level RNT predicted poorer sleep quality and greater insomnia, regardless of PTSD severity. Trauma-related RNT was also associated with greater insomnia, though the effect was moderated by PTSD severity such that it was significant for participants with low and moderate, but not severe, PTSD. Both trait- and trauma-related RNT were associated with several specific aspects of sleep quality, including: sleep disturbances, daytime dysfunction, use of sleep medications, sleep onset latency, and subjective sleep quality. CONCLUSIONS: This study demonstrates significant associations linking RNT with insomnia and sleep disturbance in trauma-exposed individuals. Clinically, results suggest that it may be helpful to target both general and trauma-related RNT in sleep interventions for trauma-exposed individuals with insomnia.

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INTRODUCTION: Non-suicidal self-injury (NSSI) is a highly prevalent maladaptive behavior, often used to cope with intense negative affect. Rumination is an emotion regulation strategy that leads to fixation on and exacerbation of (typically) negative affective states. However, studies examining the relationship between rumination and NSSI have yielded mixed results, showing high degrees of heterogeneity. METHODS: The present study conducted meta-analyses (k = 50) of the association between overall rumination and NSSI, and independent meta-analyses for each of four subtypes of rumination (general, depressive, brooding, reflection rumination). Potential moderators that may influence the magnitude of these relationships were also examined. RESULTS: A small-to-moderate positive association between rumination and NSSI was found independent of rumination subtype. Moderating effects included NSSI outcome measure and study design for overall rumination and general rumination, respectively. Race was found to moderate the relationships between both brooding and depressive rumination and NSSI, though in inverse directions. An analysis of effect heterogeneity across studies suggested that undetected moderators may be present. CONCLUSION: Results of this study support the relationships between rumination subtypes and NSSI and identify factors that may impact these relationships. Continued research is needed to understand this association, particularly in more varied subtypes of rumination and cognitive-affective moderators.

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Although a probable association between metacognitive beliefs (also termed 'metacognitions') and emotion dysregulation has been suggested in the literature, the evidence is still sparse and inconclusive. The current study aims to present a comprehensive evaluation of the literature examining the association between metacognitive beliefs and emotion dysregulation. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, a search was conducted on PubMed and Ebsco. A manual search of reference lists was also run. Search terms were 'metacognitions/metacognitive beliefs/positive metacognitive beliefs/negative metacognitive beliefs/cognitive self-consciousness/beliefs about the need to control thoughts/cognitive confidence/negative beliefs about thoughts concerning uncontrollability and danger/AND difficulties emotion regulation/emotion dysregulation'. A total of 19 studies met the inclusion criteria. In both non-clinical and clinical populations, a higher endorsement of dysfunctional metacognitive beliefs was found to be associated with emotion dysregulation and vice versa. A higher endorsement of metacognitive beliefs may be associated, either directly or via maladaptive forms of mental control (e.g., worry, rumination and suppression) to emotion dysregulation. Metacognitive beliefs could be the potential therapeutic target in clinical interventions aimed at reducing emotion regulation difficulties.

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Self-compassion is a construct of positive psychology related to personality and cognitive factors. Perfectionism and interpersonal sensitivity are prevalent personality traits among university students and are associated with low self-compassion. Further research is required to comprehend how these mechanisms work in creating self-compassion. Consequently, the current study investigated the direct and indirect relationship between perfectionism and interpersonal sensitivity with self-compassion via repetitive negative thinking. To this end, a sample of 450 students studying in Tehran during the 2022 academic year was selected as the study sample. The results indicated that perfectionism and interpersonal sensitivity demonstrate a negative direct relationship with self-compassion, while perfectionism and interpersonal sensitivity exhibit an indirect relationship with self-compassion via repetitive negative thinking. Based on the findings, it can be concluded that the relationship between perfectionism and interpersonal sensitivity with self-compassion is not straightforward and that repetitive negative thinking can mediate this relationship. The results can be used to improve methods for increasing self-compassion and paying attention to personality, and cognitive factors can be an important step toward more effective self-compassion interventions.

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Fibromyalgia can be considered to be a model of chronic pain resulting from dysregulation of pain processing. From a psychological point of view, it is possible to consider transdiagnostic processes that would participate in both the dysregulation of pain and associated emotions. OBJECTIVE: The aim of this study was to test the links that exist between the tendency to Repetitive Negative Thinking (RNT) and the anxious-depressive manifestations in fibromyalgia. More specifically, we wanted to test a double mediation model where RNT would mediate the link between pain and depression/anxiety via catastrophizing. METHOD: Eighty-two patients with fibromyalgia completed a series of questionnaires evaluating their level of depression, anxiety, disability related to pain, catastrophizing as well as various measures of Repetitive Thoughts. RESULTS: The results showed strong correlations between RNT levels, pain, and anxious-depressive manifestations in this population. Moreover, the links between pain and depression/anxiety were mediated by catastrophizing and RNT in serial. CONCLUSION: Results support the interest of studying RNT as a transdiagnostic process in fibromyalgia pain. Considering RNT in fibromyalgia allows a better understanding of tthe links that exist between pain and emotional disorders in this population and thus to better understand the psychopathological comorbidity of fibromyalgia.

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BACKGROUND: Repetitive negative thinking (RNT) is a key transdiagnostic mechanism underpinning depression and anxiety. Using "just-in-time adaptive interventions" via smartphones may disrupt RNT in real time, providing targeted and personalized intervention. OBJECTIVE: This pilot randomized controlled trial evaluates the feasibility, acceptability, and preliminary clinical outcomes and mechanisms of Mello-a fully automated, personalized, transdiagnostic, and mechanistic smartphone intervention targeting RNT in young people with depression and anxiety. METHODS: Participants with heightened depression, anxiety, and RNT were recruited via social media and randomized to receive Mello or a nonactive control over a 6-week intervention period. Assessments were completed via Zoom sessions at baseline and at 3 and 6 weeks after baseline. RESULTS: The findings supported feasibility and acceptability, with high rates of recruitment (N=55), uptake (55/64, 86% of eligible participants), and retention (52/55, 95% at 6 weeks). Engagement was high, with 90% (26/29) and 59% (17/29) of the participants in the Mello condition still using the app during the third and sixth weeks, respectively. Greater reductions in depression (Cohen d=0.50), anxiety (Cohen d=0.61), and RNT (Cohen d=0.87) were observed for Mello users versus controls. Mediation analyses suggested that changes in depression and anxiety were accounted for by changes in RNT. CONCLUSIONS: The results indicate that mechanistic, targeted, and real-time technology-based solutions may provide scalable and effective interventions that advance the treatment of youth mental ill health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621001701819; http://tinyurl.com/4d3jfj9f.

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BACKGROUND: Repetitive negative thinking (RNT), often referred to as rumination in the mood disorders literature, is a symptom dimension associated with poor prognosis and suicide in major depressive disorder (MDD). Given the transdiagnostic nature of RNT, this study aimed to evaluate the hypothesis that neurobiological substrates of RNT in MDD may share the brain mechanisms underlying obsessions, particularly those involving cortico-striatal-thalamic-cortical (CSTC) circuits. METHODS: Thirty-nine individuals with MDD underwent RNT induction during fMRI. Trait-RNT was measured by the Ruminative Response Scale (RRS) and state-RNT was measured by a visual analogue scale. We employed a connectome-wide association analysis examining the association between RNT intensity with striatal and thalamic connectivity. RESULTS: A greater RRS score was associated with hyperconnectivity of the right mediodorsal thalamus with prefrontal cortex, including lateral orbitofrontal cortex, along with Wernicke's area and posterior default mode network nodes (t = 4.66-6.70). A greater state-RNT score was associated with hyperconnectivity of the right laterodorsal thalamus with bilateral primary sensory and motor cortices, supplementary motor area, and Broca's area (t = 4.51-6.57). Unexpectedly, there were no significant findings related to the striatum. CONCLUSIONS: The present results suggest RNT in MDD is subserved by abnormal connectivity between right thalamic nuclei and cortical regions involved in both visceral and higher order cognitive processing. Emerging deep-brain neuromodulation methods may be useful to establish causal relationships between dysfunction of right thalamic-cortical circuits and RNT in MDD.

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