State rumination predicts inhibitory control failures and dysregulation of default, salience, and cognitive control networks in youth at risk of depressive relapse: Findings from the RuMeChange trial.

This is the final version. Available from Elsevier via the DOI in this record. This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Background: Trait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets. Methods: Fifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART. Results: Greater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsal-medial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyses suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination. Limitations: The correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC. Conclusions: State rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target.National Institute of Mental Healt

Self-Motion Holds a Special Status in Visual Processing

Agency plays an important role in self-recognition from motion. Here, we investigated whether our own movements benefit from preferential processing even when the task is unrelated to self-recognition, and does not involve agency judgments. Participants searched for a moving target defined by its known shape among moving distractors, while continuously moving the computer mouse with one hand. They thereby controlled the motion of one item, which was randomly either the target or any of the distractors, while the other items followed pre-recorded motion pathways. Performance was more accurate and less prone to degradation as set size increased when the target was the self-controlled item. An additional experiment confirmed that participant-controlled motion was not physically more salient than motion recorded offline. We found no evidence that self-controlled items captured attention. Taken together, these results suggest that visual events are perceived more accurately when they are the consequences of our actions, even when self-motion is task irrelevant

Self-injury in adolescence is associated with greater behavioral risk avoidance, not risk-taking.

This is the final version. Available from MDPI via the DOI in this record. Data Availability Statement: The study is registered on clinicaltrials.gov (NCT03859297), which will be updated with the published protocol and the study results and associated publications. Deidentified data and results will be submitted to the National Database for Clinical Trials Related to Mental Illness (NDCT).Strategies to link impulsivity and self-injurious behaviors (SIBs) show highly variable results, and may differ depending on the impulsivity measure used. To better understand this lack of consistency, we investigated correlations between self-report and behavioral impulsivity, inhibitory control, SIBs, and rumination. We included participants aged 13-17 years with either current or remitted psychopathology who have (n = 31) and who do not have (n = 14) a history of SIBs. Participants completed self-report measures of impulsivity, the Rumination Responsiveness Scale (RRS), and two behavioral measures of impulsivity: the Balloon Analogue Risk Task (BART) and Parametric Go/No-Go (PGNG). Lifetime SIBs were positively associated with self-reported impulsivity, specifically positive and negative urgency. However, individuals with greater lifetime SIBs demonstrated greater risk aversion (lower impulsivity) as measured by the BART, whereas there was no relation between lifetime SIBs and PGNG performance. There was no relation between rumination and behavioral impulsivity, although greater rumination was associated with higher negative urgency. Future research examining the role of SIBs in the context of active versus remitted psychopathology is warranted. Because most adolescents were remitted from major depressive disorder at the time of study, follow-up studies can determine if lower risk-taking may aid individuals with more prior SIBs to achieve and maintain a remitted state.National Institute of Mental Health (NIMH

Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care.

Osteoarthritis is the most common joint disease diagnosed in veterinary medicine and poses considerable challenges to canine welfare. This study aimed to investigate prevalence, duration and risk factors of appendicular osteoarthritis in dogs under primary veterinary care in the UK. The VetCompassTM programme collects clinical data on dogs attending UK primary-care veterinary practices. The study included all VetCompassTM dogs under veterinary care during 2013. Candidate osteoarthritis cases were identified using multiple search strategies. A random subset was manually evaluated against a case definition. Of 455,557 study dogs, 16,437 candidate osteoarthritis cases were identified; 6104 (37%) were manually checked and 4196 (69% of sample) were confirmed as cases. Additional data on demography, clinical signs, duration and management were extracted for confirmed cases. Estimated annual period prevalence (accounting for subsampling) of appendicular osteoarthritis was 2.5% (CI95: 2.4-2.5%) equating to around 200,000 UK affected dogs annually. Risk factors associated with osteoarthritis diagnosis included breed (e.g. Labrador, Golden Retriever), being insured, being neutered, of higher bodyweight and being older than eight years. Duration calculation trials suggest osteoarthritis affects 11.4% of affected individuals' lifespan, providing further evidence for substantial impact of osteoarthritis on canine welfare at the individual and population level

Rumination-Focused Cognitive Behavioral Therapy Reduces Rumination and Targeted Cross-network Connectivity in Youth With a History of Depression: Replication in a Preregistered Randomized Clinical Trial

This is the final version. Available from Elsevier via the DOI in this record. Background: Rumination-focused cognitive behavioral therapy (RF-CBT) is designed to reduce depressive rumination or the habitual tendency to dwell on experiences in a repetitive, negative, passive, and global manner. RF-CBT uses functional analysis, experiential exercises, and repeated practice to identify and change the ruminative habit. This preregistered randomized clinical trial (NCT03859297, R61) is a preregistered replication of initial work. We hypothesized a concurrent reduction of both self-reported rumination and cross-network connectivity between the left posterior cingulate cortex and right inferior frontal and inferior temporal gyri. Methods: Seventy-six youths with a history of depression and elevated rumination were randomized to 10 to 14 sessions of RF-CBT (n = 39; 34 completers) or treatment as usual (n = 37; 28 completers). Intent-to-treat analyses assessed pre-post change in rumination response scale and in functional connectivity assessed using two 5 minute, 12 second runs of resting-state functional magnetic resonance imaging. Results: We replicated previous findings: a significant reduction in rumination response scale and a reduction in left posterior cingulate cortex to right inferior frontal gyrus/inferior temporal gyrus connectivity in participants who received RF-CBT compared with those who received treatment as usual. Reductions were large (z change = 0.84; 0.73, respectively [ps < .05]). Conclusions: This adolescent clinical trial further demonstrates that depressive rumination is a brain-based mechanism that is modifiable via RF-CBT. Here, we replicated that RF-CBT reduces cross-network connectivity, a possible mechanism by which rumination becomes less frequent, intense, and automatic. This National Institute of Mental Health-funded fast-fail study continues to the R33 phase during which treatment-specific effects of RF-CBT will be compared with relaxation therapy.National Institute of Mental HealthHuntsman Mental Health Institut

How do parents experience being asked to enter a child in a randomised controlled trial?

<p>Abstract</p> <p>Background</p> <p>As the number of randomised controlled trials of medicines for children increases, it becomes progressively more important to understand the experiences of parents who are asked to enrol their child in a trial. This paper presents a narrative review of research evidence on parents' experiences of trial recruitment focussing on qualitative research, which allows them to articulate their views in their own words.</p> <p>Discussion</p> <p>Parents want to do their best for their children, and socially and legally their role is to care for and protect them yet the complexities of the medical and research context can challenge their fulfilment of this role. Parents are simultaneously responsible for their child and cherish this role yet they are dependent on others when their child becomes sick. They are keen to exercise responsibility for deciding to enter a child in a trial yet can be fearful of making the 'wrong' decision. They make judgements about the threat of the child's condition as well as the risks of the trial yet their interpretations often differ from those of medical and research experts. Individual pants will experience these and other complexities to a greater or lesser degree depending on their personal experiences and values, the medical situation of their child and the nature of the trial. Interactions at the time of trial recruitment offer scope for negotiating these complexities if practitioners have the flexibility to tailor discussions to the needs and situation of individual parents. In this way, parents may be helped to retain a sense that they have acted as good parents to their child whatever decision they make.</p> <p>Summary</p> <p>Discussing randomised controlled trials and gaining and providing informed consent is challenging. The unique position of parents in giving proxy consent for their child adds to this challenge. Recognition of the complexities parents face in making decisions about trials suggests lines for future research on the conduct of trials, and ultimately, may help improve the experience of trial recruitment for all parties.</p

The Arabidopsis leucine-rich repeat receptor kinase MIK2/LRR-KISS connects cell wall integrity sensing, root growth and response to abiotic and biotic stresses

Plants actively perceive and respond to perturbations in their cell walls which arise during growth, biotic and abiotic stresses. However, few components involved in plant cell wall integrity sensing have been described to date. Using a reverse-genetic approach, we identified the Arabidopsis thaliana leucine-rich repeat receptor kinase MIK2 as an important regulator of cell wall damage responses triggered upon cellulose biosynthesis inhibition. Indeed, loss-of-function mik2 alleles are strongly affected in immune marker gene expression, jasmonic acid production and lignin deposition. MIK2 has both overlapping and distinct functions with THE1, a malectin-like receptor kinase previously proposed as cell wall integrity sensor. In addition, mik2 mutant plants exhibit enhanced leftward root skewing when grown on vertical plates. Notably, natural variation in MIK2 (also named LRR-KISS) has been correlated recently to mild salt stress tolerance, which we could confirm using our insertional alleles. Strikingly, both the increased root skewing and salt stress sensitivity phenotypes observed in the mik2 mutant are dependent on THE1. Finally, we found that MIK2 is required for resistance to the fungal root pathogen Fusarium oxysporum. Together, our data identify MIK2 as a novel component in cell wall integrity sensing and suggest that MIK2 is a nexus linking cell wall integrity sensing to growth and environmental cues

Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions

Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.</p> <p>Methods/Design</p> <p>STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.</p> <p>Clinical Trials Registry</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01141608">NCT01141608</a></p> <p><url>http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1</url></p