The 'revolving door' of mental illness: A meta-analysis and systematic review of current versus lifetime rates of psychological disorders.

OBJECTIVES: Therapists have long observed a phenomenon referred to as the 'revolving door' of mental health services, in which individuals often develop, seek treatment for, and recover from multiple mental illnesses across their life. However, this has not been systematically examined. If this phenomenon is widespread, one would expect that the number of lifetime disorders would exceed that of current disorders. The aim of this meta-analysis was to test this hypothesis. METHODS: A search was conducted of the following databases: MEDLINE, PsycINFO and Web of Science. In total, 38 studies were included in the current review; 27 of these contained sufficient quantitative data to be included in the meta-analysis, addressing the primary research aim. The remaining 11 studies were included in the systematic review only. RESULTS: Meta-analyses of the 27 studies indicated that the average number of lifetime disorders was 1.84 times that of current disorders. Previous treatment significantly moderated this relationship, while the clinical nature of the sample did not. Examination of the remaining studies revealed common temporal sequences, indicating disorders which typically develop first or consequently to other disorders. CONCLUSIONS: These findings provide support for the revolving door of mental illness, suggesting a need for transdiagnostic treatments and broader conceptualisation of relapse prevention.

Benign or painful? The interpretation of pain and fear of progression in rheumatoid arthritis.

ABSTRACT: People with chronic pain tend to interpret ambiguous information as health-related, more so than people without. In this study, we aimed to investigate whether people with rheumatoid arthritis (RA) exhibit this interpretation bias and whether it is associated with fear of disease progression (FoP). The interpretation biases of people with RA (n = 164) were compared with an age- and gender-matched control group. We hypothesized that (1) people with RA would have larger interpretation biases than people without; (2) those who scored in the clinical range for FoP would have larger interpretation bias than those who did not; (3) interpretation bias would moderate the relationship between pain severity and FoP; and (4) interpretation bias would explain variance in FoP above and beyond other established predictors. Our results confirmed that people with RA were more likely to interpret ambiguous information as health-related compared with people without RA. This effect was more pronounced for the RA subgroup with clinically significant FoP than those scoring in the normal range. We did not find evidence to suggest interpretation bias moderated the relationship between pain and FoP or that FoP added to the variance of other known predictors. Our results indicate that interpretation bias is common amongst people with RA and is associated with FoP. Further research is required to illuminate the exact nature of this relationship.

The development and validation of the Worries About Recurrence or Progression Scale (WARPS).

OBJECTIVES: Worry about recurrence or progression is a common concern among people with chronic physical illnesses. Although there are options to measure the fear of cancer recurrence and other illness-specific measures, there is only one transdiagnostic measure of fear of progression, which does not assess the fear of recurrence or relapse. DESIGN: A multi-phase study outlining the development and validation of a novel transdiagnostic measure of fear of recurrence or progression, the Worries About Recurrence and Progression Scale (WARPS). METHOD: From a prior systematic review, we used quotes from people with lived experience to generate 55 items. Next, we piloted the items with 10 people with a range of chronic conditions, leading to a final total of 57 items. We then recruited four groups of people with cardiac disease, rheumatic disease, diabetes and respiratory disease (n = 804). An exploratory factor analysis in a randomly split sample resulted in an 18 item, single factor scale. We then performed confirmatory factor analysis on these 18 items in the remaining sample. RESULTS: The 18-item WARPS demonstrated good construct validity, internal consistency and test-retest reliability. Specifically, the WARPS was strongly correlated with the Fear of Progression Questionnaire, and with illness-specific fears. Significant, moderate correlations were observed with depression, anxiety, stress, and death anxiety. The WARPS demonstrated the validity and reliability amongst people with four of the most common chronic conditions and the factor structure was invariant across genders. CONCLUSION: The WARPS is a valid and reliable tool to measure transdiagnostic worries about recurrence and progression.

A synthesis of meta-analyses of mindfulness-based interventions in pain.

ABSTRACT: Mindfulness interventions have become popular in recent decades, with many trials, systematic reviews, and meta-analyses of the impact of mindfulness-based interventions (MBIs) on pain. Although many meta-analyses provide support for MBIs, the results are more mixed than they at first appear. The aim of this umbrella review was to determine the strength of evidence for MBIs by synthesizing available meta-analyses in pain. We conducted a systematic search in 5 databases and extracted data from published meta-analyses as the unit of analysis. For each outcome, we reported the range of effect sizes observed across studies and identified the largest meta-analysis as the "representative" study. We separately analysed effect sizes for different pain conditions, different types of MBIs, different control groups, and different outcomes. We identified 21 meta-analyses that included 127 unique studies. According to Assessment of Multiple Systematic Review ratings, the meta-analyses ranged from very strong to weak. Overall, there was an impact of MBIs on pain severity, anxiety, and depression but not pain interference or disability. When conditions were considered in isolation, only fibromyalgia and headache benefited significantly from MBIs. Mindfulness-based interventions were more efficacious for pain severity than passive control conditions but not active control conditions. Only pain severity and anxiety were affected by MBIs at follow-up. Overall, our results suggest that individual meta-analyses of MBIs may have overestimated the efficacy of MBIs in a range of conditions. Mindfulness-based interventions likely have a role in pain management but should not be considered a panacea.

A cross-sectional study of existential concerns and fear of progression in people with Rheumatoid Arthritis.

OBJECTIVES: People with rheumatoid arthritis (RA) have higher levels of fear of disease progression (FOP) than cancer survivors. In cancer, FOP is inextricably linked with existential concerns. However, this has not been investigated in people with RA. METHODS: We recruited 165 people with RA (96%F) who volunteered for a treatment trial of psychological intervention. Participants completed the Existential Concerns Questionnaire (ECQ) and questionnaires measuring constructs associated with FOP in cancer. We created groups of people with RA, with and without clinically significant levels of FOP (clinical and control groups) and compared their existential concerns. We hypothesized that existential concerns would add to the variance in FOP over and above pain, psychopathology, and disability. RESULTS: Nearly two-thirds of people with RA scored in the clinical range for FOP. The clinical group had higher levels of all existential concerns than the control group. When subscales of the ECQ were entered into a multiple regression with FOP as the dependent variable, death anxiety, meaninglessness and guilt domains accounted for significant variance in FOP. Moreover, when added to a regression equation controlling all other variables, existential concerns continued to account for unique variance in FOP (t = 2.712, p = 0.007). CONCLUSION: Existential concerns were strongly associated with FOP. While this cross-sectional study cannot determine whether existential concerns underlie FOP in RA, these results show robust relationships that warrant future investigation.

Plant-Environment Response Pathway Regulation Uncovered by Investigating Non-Typical Legume Symbiosis and Nodulation.

Nitrogen is an essential element needed for plants to survive, and legumes are well known to recruit rhizobia to fix atmospheric nitrogen. In this widely studied symbiosis, legumes develop specific structures on the roots to host specific symbionts. This review explores alternate nodule structures and their functions outside of the more widely studied legume-rhizobial symbiosis, as well as discussing other unusual aspects of nodulation. This includes actinorhizal-Frankia, cycad-cyanobacteria, and the non-legume Parasponia andersonii-rhizobia symbioses. Nodules are also not restricted to the roots, either, with examples found within stems and leaves. Recent research has shown that legume-rhizobia nodulation brings a great many other benefits, some direct and some indirect. Rhizobial symbiosis can lead to modifications in other pathways, including the priming of defence responses, and to modulated or enhanced resistance to biotic and abiotic stress. With so many avenues to explore, this review discusses recent discoveries and highlights future directions in the study of nodulation.

Rhizobial nitrogen fixation efficiency shapes endosphere bacterial communities and Medicago truncatula host growth.

BACKGROUND: Despite the knowledge that the soil-plant-microbiome nexus is shaped by interactions amongst its members, very little is known about how individual symbioses regulate this shaping. Even less is known about how the agriculturally important symbiosis of nitrogen-fixing rhizobia with legumes is impacted according to soil type, yet this knowledge is crucial if we are to harness or improve it. We asked how the plant, soil and microbiome are modulated by symbiosis between the model legume Medicago truncatula and different strains of Sinorhizobium meliloti or Sinorhizobium medicae whose nitrogen-fixing efficiency varies, in three distinct soil types that differ in nutrient fertility, to examine the role of the soil environment upon the plant-microbe interaction during nodulation. RESULTS: The outcome of symbiosis results in installment of a potentially beneficial microbiome that leads to increased nutrient uptake that is not simply proportional to soil nutrient abundance. A number of soil edaphic factors including Zn and Mo, and not just the classical N/P/K nutrients, group with microbial community changes, and alterations in the microbiome can be seen across different soil fertility types. Root endosphere emerged as the plant microhabitat more affected by this rhizobial efficiency-driven community reshaping, manifested by the accumulation of members of the phylum Actinobacteria. The plant in turn plays an active role in regulating its root community, including sanctioning low nitrogen efficiency rhizobial strains, leading to nodule senescence in particular plant-soil-rhizobia strain combinations. CONCLUSIONS: The microbiome-soil-rhizobial dynamic strongly influences plant nutrient uptake and growth, with the endosphere and rhizosphere shaped differentially according to plant-rhizobial interactions with strains that vary in nitrogen-fixing efficiency levels. These results open up the possibility to select inoculation partners best suited for plant, soil type and microbial community. Video Abstract.

"Life's too short to be small": An experimental exploration of the relationship between death anxiety and muscle dysmorphia symptoms.

Growing research demonstrates that death anxiety is strongly associated with numerous mental health conditions. It is possible that death anxiety may similarly contribute to behaviours associated with muscle dysmorphia (MD). The current pre-registered study examined this possibility in 322 young men with an interest in health and fitness. The mortality salience paradigm was used to experimentally examine whether reminders of death increased behaviours relevant to MD. Measures of MD symptoms and death anxiety were also completed by participants. Contrary to expectations, reminders of death did not significantly increase willingness to trial workout supplements, or dissatisfaction with current muscularity. Participants reminded of death reported lower intention to exercise in the near future, compared to the control condition. Moreover, death reminders did not lead to significantly larger portion sizes being chosen. However, in post-hoc analyses, men with high, but not low, MD symptoms did choose larger portions after being primed with death. Lastly, positive correlations were found between self-report measures of MD symptoms and two measures of death anxiety. Cumulatively, these results suggest that while fears of death may be associated with self-reported MD symptoms, they may not drive excessive exercise, nor body dissatisfaction in men.

The relationship between expectancy, anxiety, and the nocebo effect: a systematic review and meta-analysis with recommendations for future research.

Despite the theoretical prominence of expectancy and anxiety as potential mechanisms of the nocebo effect, not all studies measure expectancy and/or anxiety, and there are inconsistent findings among those that do. The present study sought to systematically review and meta-analyse available data to evaluate the relationship between expectancy, anxiety and the nocebo effect. The two key questions were: (1) whether nocebo manipulations influence expectancy and anxiety; and (2) whether expectancy and anxiety are associated with the subsequent nocebo effect. Fifty-nine independent studies (n = 3129) were identified via database searches to 1st August 2021. Nocebo manipulations reliably increased negative expectancy with a large effect (g = .837) and state anxiety with a small effect (g = .312). Changes in expectancy and state anxiety due to the nocebo manipulation were associated with larger nocebo effects (r = .376 and .234, respectively). However, there was no significant association between dispositional anxiety and the nocebo effect. These findings support theories that rely on situationally-induced expectancy and anxiety, but not dispositional anxiety, to explain nocebo effects. Importantly, being malleable, these findings suggest that interventions that target maladaptive negative expectancies and state anxiety could be beneficial for reducing the harm nocebo effects cause across health settings. Recommendations for future research are discussed.

Are Fear Campaigns Effective for Increasing Adherence to COVID-Related Mitigation Measures?

BACKGROUND: Using fear to increase the uptake of preventative health behaviours is a longstanding practice, which could be useful in mitigating the spread of COVID-19. However, the impact of fear campaigns beyond behavioural outcomes has rarely been considered. It is possible that these threatening health messages could heighten health-related anxiety by inducing a tendency to interpret ambiguous stimuli in a threatening manner. This research aimed to evaluate the effects of fear-based articles about COVID-19, on intentions to adhere to mitigation measures and interpretation bias-a core maintenance factor in health anxiety. METHOD: Two pilot studies were conducted with the aim of validating our novel COVID-related measures and assessing engagement with the threat manipulation. Following this, 375 community members were recruited through social media for the main study. Participants were then randomly allocated to read an article about COVID which was manipulated on both threat and efficacy. After reading the article, participants then completed measures of interpretation bias and intentions to engage in COVID-19 mitigation measures. RESULTS: Although the threatening articles consistently produced greater COVID-related threat, they only generated a stronger interpretation bias in the first pilot study. Importantly, threat-based communications failed to enhance intentions to perform mitigation measures in any of the studies. Likewise, reading an article which bolstered self-efficacy did not increase intentions, compared to reading a low efficacy article. CONCLUSION: This research suggests that fear appeals are unlikely to increase intentions to perform COVID-related mitigation measures.

Polymer nanoparticles pass the plant interface.

As agriculture strives to feed an ever-increasing number of people, it must also adapt to increasing exposure to minute plastic particles. To learn about the accumulation of nanoplastics by plants, we prepared well-defined block copolymer nanoparticles by aqueous dispersion polymerisation. A fluorophore was incorporated via hydrazone formation and uptake into roots and protoplasts of Arabidopsis thaliana was investigated using confocal microscopy. Here we show that uptake is inversely proportional to nanoparticle size. Positively charged particles accumulate around root surfaces and are not taken up by roots or protoplasts, whereas negatively charged nanoparticles accumulate slowly and become prominent over time in the xylem of intact roots. Neutral nanoparticles penetrate rapidly into intact cells at the surfaces of plant roots and into protoplasts, but xylem loading is lower than for negative nanoparticles. These behaviours differ from those of animal cells and our results show that despite the protection of rigid cell walls, plants are accessible to nanoplastics in soil and water.

Randomised controlled trial of cognitive behaviour therapy versus mindfulness for people with rheumatoid arthritis with and without a history of recurrent depression: study protocol and design.

INTRODUCTION: Psychosocial treatments have been shown to benefit people with rheumatoid arthritis (RA) on various outcomes. Two evidence-based interventions are cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR). However, these interventions have been compared only once. Results showed that CBT outperformed MBSR on some outcomes, but MBSR was more effective for people with RA with a history of recurrent depression, with efficacy being moderated by history of depressive episodes. However, this was a post-hoc finding based on a small subsample. We aim to examine whether a history of recurrent depression will moderate the relative efficacy of these treatments when delivered online. METHODS AND ANALYSIS: This study is a randomised controlled trial comparing CBT and MBSR delivered online with a waitlist control condition. History of recurrent depressive episodes will be assessed at baseline. The primary outcome will be pain interference. Secondary outcomes will include pain intensity, RA symptoms, depressive symptoms and anxiety symptoms. Outcome measures will be administered at baseline, post-treatment and at 6 months follow-up. We aim to recruit 300 participants, and an intention-to-treat analysis will be used. Linear mixed models will be used, with baseline levels of treatment outcomes as the covariate, and group and depressive status as fixed factors. The results will demonstrate whether online CBT and MBSR effectively improve outcomes among people with RA. Importantly, this trial will determine whether one intervention is more efficacious, and whether prior history of depression moderates this effect. ETHICS AND DISSEMINATION: The trial has been approved by the Human Research Ethics Committee of the University of Sydney (2021/516). The findings will be subject to publication irrespective of the final results of the study, and based on the outcomes presented in this protocol. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000997853p).

Elucidating connections between the strigolactone biosynthesis pathway, flavonoid production and root system architecture in Arabidopsis thaliana.

Strigolactones (SLs) are the most recently discovered phytohormones, and their roles in root architecture and metabolism are not fully understood. Here, we investigated four MORE AXILLARY GROWTH (MAX) SL mutants in Arabidopsis thaliana, max3-9, max4-1, max1-1 and max2-1, as well as the SL receptor mutant d14-1 and karrikin receptor mutant kai2-2. By characterising max2-1 and max4-1, we found that variation in SL biosynthesis modified multiple metabolic pathways in root tissue, including that of xyloglucan, triterpenoids, fatty acids and flavonoids. The transcription of key flavonoid biosynthetic genes, including TRANSPARENT TESTA4 (TT4) and TRANSPARENT TESTA5 (TT5) was downregulated in max2 roots and seedlings, indicating that the proposed MAX2 regulation of flavonoid biosynthesis has a widespread effect. We found an enrichment of BRI1-EMS-SUPPRESSOR 1 (BES1) targets amongst genes specifically altered in the max2 mutant, reflecting that the regulation of flavonoid biosynthesis likely occurs through the MAX2 degradation of BES1, a key brassinosteroid-related transcription factor. Finally, flavonoid accumulation decreased in max2-1 roots, supporting a role for MAX2 in regulating both SL and flavonoid biosynthesis.

Plant circadian clock control of Medicago truncatula nodulation via regulation of nodule cysteine-rich peptides.

Legumes house nitrogen-fixing endosymbiotic rhizobia in specialized polyploid cells within root nodules, which undergo tightly regulated metabolic activity. By carrying out expression analysis of transcripts over time in Medicago truncatula nodules, we found that the circadian clock enables coordinated control of metabolic and regulatory processes linked to nitrogen fixation. This involves the circadian clock-associated transcription factor LATE ELONGATED HYPOCOTYL (LHY), with lhy mutants being affected in nodulation. Rhythmic transcripts in root nodules include a subset of nodule-specific cysteine-rich peptides (NCRs) that have the LHY-bound conserved evening element in their promoters. Until now, studies have suggested that NCRs act to regulate bacteroid differentiation and keep the rhizobial population in check. However, these conclusions came from the study of a few members of this very large gene family that has complex diversified spatio-temporal expression. We suggest that rhythmic expression of NCRs may be important for temporal coordination of bacterial activity with the rhythms of the plant host, in order to ensure optimal symbiosis.

Regulation of Resource Partitioning Coordinates Nitrogen and Rhizobia Responses and Autoregulation of Nodulation in Medicago truncatula.

Understanding how plants respond to nitrogen in their environment is crucial for determining how they use it and how the nitrogen use affects other processes related to plant growth and development. Under nitrogen limitation the activity and affinity of uptake systems is increased in roots, and lateral root formation is regulated in order to adapt to low nitrogen levels and scavenge from the soil. Plants in the legume family can form associations with rhizobial nitrogen-fixing bacteria, and this association is tightly regulated by nitrogen levels. The effect of nitrogen on nodulation has been extensively investigated, but the effects of nodulation on plant nitrogen responses remain largely unclear. In this study, we integrated molecular and phenotypic data in the legume Medicago truncatula and determined that genes controlling nitrogen influx are differently expressed depending on whether plants are mock or rhizobia inoculated. We found that a functional autoregulation of nodulation pathway is required for roots to perceive, take up, and mobilize nitrogen as well as for normal root development. Our results together revealed that autoregulation of nodulation, root development, and the location of nitrogen are processes balanced by the whole plant system as part of a resource-partitioning mechanism.