Advancing randomized controlled trial methodologies: The place of innovative trial design in eating disorders research.

Randomized controlled trials can be used to generate evidence on the efficacy and safety of new treatments in eating disorders research. Many of the trials previously conducted in this area have been deemed to be of low quality, in part due to a number of practical constraints. This article provides an overview of established and more innovative clinical trial designs, accompanied by pertinent examples, to highlight how design choices can enhance flexibility and improve efficiency of both resource allocation and participant involvement. Trial designs include individually randomized, cluster randomized, and designs with randomizations at multiple time points and/or addressing several research questions (master protocol studies). Design features include the use of adaptations and considerations for pragmatic or registry-based trials. The appropriate choice of trial design, together with rigorous trial conduct, reporting and analysis, can establish high-quality evidence to advance knowledge in the field. It is anticipated that this article will provide a broad and contemporary introduction to trial designs and will help researchers make informed trial design choices for improved testing of new interventions in eating disorders. PUBLIC SIGNIFICANCE: There is a paucity of high quality randomized controlled trials that have been conducted in eating disorders, highlighting the need to identify where efficiency gains in trial design may be possible to advance the eating disorder research field. We provide an overview of some key trial designs and features which may offer solutions to practical constraints and increase trial efficiency.

A new network analysis model in anorexia nervosa patients based on self-reported eating disorder symptoms, psychological distress, and cognitive flexibility.

OBJECTIVES: Cognitive flexibility and psychological distress, such as depression and anxiety, have been implicated in the aetiology of Anorexia Nervosa (AN). Despite the known associations between eating disorder (ED) symptoms, depression, anxiety, and cognitive flexibility, the specific pathways that connect these constructs are unclear. We therefore used network analysis to examine the relationship between these symptoms in an AN sample. METHODS: One hundred and ninety-three treatment-seeking individuals diagnosed with AN (95.6% female, M = 26.89 [SD = 9.45] years old) completed self-report measures assessing depression, anxiety, cognitive flexibility, and ED symptoms. To determine each symptom's influence in the network, we calculated the expected influence. RESULTS: The two relationships with the greatest edges were those between (1) weight/shape concerns and eating/dietary restraint and (2) weight/shape concerns and psychological distress (a measure that combined depression and anxiety). Cognitive flexibility was not connected to weight/shape concerns but had negative partial associations with eating concerns/dietary restraint and psychological distress. There was also a slight, non-zero connection between eating concerns/dietary restraint and psychological distress. CONCLUSIONS: The findings underscore the importance of weight/shape, eating/dietary concerns, and psychological distress in the AN network and suggest that addressing cognitive flexibility may be a useful target for eating concerns/dietary restraint and psychological distress. Future studies assessing the longitudinal course of psychopathology within the AN network structure may help in identifying whether specific symptoms function as risk factors or maintaining factors for this co-occurrence.

Striving to support the supporters: A mixed methods evaluation of the strive support groups for caregivers of individuals with an eating disorder.

This mixed-methods study evaluated a peer-led support group for ED caregivers; the Eating Disorders Families Australia strive support groups. Quantitatively, 110 past or current strive attendees completed an online survey assessing their own and their care recipients' demographic profiles, strive's impact on caregiving experiences, and caregivers' psychological distress, burden, caregiving skills and self-efficacy. Qualitative assessment comprised open-ended survey questions about caregivers' strive experiences, reinforced by in-depth focus group assessment of nine participants. Quantitative analyses revealed that participants felt more confident and supported, and less isolated in their caregiving since attending strive. Caregivers displayed mid-range psychological distress and caregiver burden, and moderate caregiver skills and self-efficacy. Qualitatively, the most helpful aspects of strive were the shared experience among participants, education, and support. The most difficult elements were emotional distress and overly dominant members. Reflections discussed the necessity of caregiver support and factors impacting strive attendance. Participants recommended resuming face-to-face contact and differentiating groups based on participant characteristics (e.g. care recipients' age/stage of illness). The current findings provide support for the importance and overall positive contribution of support groups led by caregivers, such as strive.

Eating behaviours and personality characteristics of clinicians and researchers working in eating disorders.

Disturbances in eating behaviours and differences in personality characteristics, such as perfectionism, cognitive flexibility, and obsessive-compulsive behaviours, are commonly reported in individuals with eating disorders (ED) and can influence the development and maintenance of EDs. The presence of these characteristics in ED professionals may also have an influence on their patients. The aim of this study was to gain a better understanding of the presence of these behaviours and characteristics in ED clinicians/researchers (EDCR). This study examined whether these constructs differed amongst 83 EDCR and 47 general mental health clinicians/researchers (MHCR), who completed an online survey, measuring eating disorder symptomology, orthorexia nervosa, perfectionism, cognitive flexibility, and obsessive-compulsive traits. Significantly less dietary restraint, eating concerns and orthorexia nervosa behaviours, but significantly poorer ability to seek out alternative solutions (i.e. a component of cognitive flexibility) were found in the EDCR group compared with the MHCR group. Moderation analysis found no effect of ED history on the relationship between eating behaviours and group. These results suggest that working in the ED field may be a protective factor against developing certain disordered eating behaviours. However, poorer cognitive flexibility may adversely impact EDCRs, and should be considered when carrying out their clinical and/or research duties.

Psychiatric comorbidity and severity in anorexia nervosa: a comparative study of the DSM-5, the ICD-11, and overvaluation of Weight/Shape severity ratings.

This study assessed the rate of a.) the total and b.) specific psychiatric comorbidities among the three severity ratings for Anorexia Nervosa (AN): DSM-5, ICD-11 and overvaluation of weight and shape (OWS). The sample comprised 312 treatment-seeking patients with AN (mean age = 26.9). Weight and height were taken at intake to calculate BMI, the foundation for the DSM-5 and ICD-11 severity indices. The EDE-Q was used to assess OWS, and the Mini International Neuropsychiatric Interview was conducted to assess psychiatric comorbidities. For the DSM-5, the mild severity group showed a higher total number of psychiatric comorbidities, especially for panic, social anxiety, generalised anxiety, and post-traumatic stress disorders compared to the severe and extremely severe groups. ICD-11 and OWS severity groups did not significantly differ in total comorbidities, except for major depressive disorder and obsessive-compulsive disorders being more prevalent in the "significantly low BMI" ICD-11 group. The high OWS group displayed a notably higher rate of major depressive disorder than the low OWS group. The study underscores inconsistent patterns across the three severity systems, emphasising the need to recognise the current limitations of the assessed severity classification systems in AN assessment and guiding treatment.

Challenges and priorities for researching the gut microbiota in individuals living with anorexia nervosa.

OBJECTIVE: The gut microbiota is implicated in several symptoms and biological pathways relevant to anorexia nervosa (AN). Investigations into the role of the gut microbiota in AN are growing, with a specific interest in the changes that occur in response to treatment. Findings suggest that microbial species may be associated with some of the symptoms common in AN, such as depression and gastrointestinal disturbances (GID). Therefore, researchers believe the gut microbiota may have therapeutic relevance. Whilst research in this field is rapidly expanding, the unique considerations relevant to conducting gut microbiota research in individuals with AN must be addressed. METHOD: We provide an overview of the published literature investigating the relationship between the gut microbiota and symptoms and behaviors present in AN, discuss important challenges in gut microbiota research, and offer recommendations for addressing these. We conclude by summarizing research design priorities for the field to move forward. RESULTS: Several ways exist to reduce participant burden and accommodate challenges when researching the gut microbiota in individuals with AN. DISCUSSION: Recommendations from this article are foreseen to encourage scientific rigor and thoughtful protocol planning for microbiota research in AN, including ways to reduce participant burden. Employing such methods will contribute to a better understanding of the role of the gut microbiota in AN pathophysiology and treatment. PUBLIC SIGNIFICANCE: The field of gut microbiota research is rapidly expanding, including the role of the gut microbiota in anorexia nervosa. Thoughtful planning of future research will ensure appropriate data collection for meaningful interpretation while providing a positive experience for the participant. We present current challenges, recommendations for research design and priorities to facilitate the advancement of research in this field.

Assessing severity in anorexia nervosa: Do the DSM-5 and an alternative severity rating based on overvaluation of weight and shape severity differ in psychological and biological correlates?

OBJECTIVE: This study evaluated the severity ratings for anorexia nervosa (AN) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and an alternative severity rating based on overvaluation of weight/shape, on a range of psychological and biological variables. METHOD: A sample of 312 treatment-seeking patients with AN (mean age = 25.3, SD = 7.6; mean BMI = 16.8 kg/m2 , SD = 2.4) were categorised using both DSM-5 severity levels (mild/moderate/severe/extreme) and weight/shape (low/high) overvaluation. The severity categories were compared on a range of psychological (e.g., eating psychopathology) and biological (e.g., sodium) variables. RESULTS: Results showed that the overvaluation of weight/shape appeared better at indexing the level of severity in psychological variables among patients with AN compared to the DSM-5 severity rating with moderate to large effect sizes. Moreover, the DSM-5 mild and moderate severity groups experienced significantly higher eating and general psychopathology than the severe and extreme groups. Finally, neither the DSM-5 nor the weight/shape severity groups differed on any of the biological variables. CONCLUSIONS: This study provided no support for the DSM-5 severity rating for AN, while initial support was found for the weight/shape overvaluation approach in indexing psychological but not biological correlates.

Investigating differences in cognitive flexibility, clinical perfectionism, and eating disorder-specific rumination across anorexia nervosa illness states.

INTRODUCTION: Cognitive inflexibility, clinical perfectionism, and eating disorder (ED)-specific rumination are common characteristics reported in anorexia nervosa (AN) and may contribute to the maintenance of the illness. It is suggested that clinical perfectionism and rumination may mediate the relationship between cognitive flexibility and AN pathology; however, research to date has not investigated all these factors together. The aim of the current study was to explore the relationships between these factors and how they may relate to ED symptoms in AN. METHODS: Participants included 15 women with a current diagnosis of AN, 12 women who had a past diagnosis of AN and were currently weight-restored, and 15 healthy controls (HCs). RESULTS: The results revealed that participants with both acute and weight-restored AN self-reported poorer cognitive flexibility than HCs, but the groups did not differ in performance on objective assessments of cognitive flexibility. Participants with AN also reported significantly greater clinical perfectionism and ED-specific rumination than HC. A parallel mediation analysis found that ED-specific rumination mediated the relationship between subjective cognitive flexibility and ED symptoms. Further, subjective cognitive flexibility directly influenced ED symptoms. However, the mediation model was not significant for objective cognitive flexibility. CONCLUSION: The findings of this study have implications for potential treatment barriers and factors which might contribute to the risk of relapse.

Eating disorders in young people.

OBJECTIVE: Eating disorders (EDs) have their onset most frequently in adolescence and young adulthood. Treatment for EDs lack efficacy, and we have made little progress in improving outcomes for patients over the course of the last several decades. As with other mental health conditions, early intervention may greatly improve outcomes, yet, little research exists in this area. CONCLUSIONS: More effective evidence-based treatments are sorely needed for EDs, particularly for early stages of the illness to minimise the potential harms of treatment and long-standing illness. Treatment service models would also benefit from taking an approach that ensures continuation of care from adolescence to young adulthood.

Over a decade of an eating disorders treatment program: Where to from here?

OBJECTIVE: Currently available treatments for eating disorders lack efficacy resulting in poor outcomes for patients. In this paper, we describe a number of issues that we have identified in our clinical service, which are not unique to our treatment program. CONCLUSIONS: The issues described are common among eating disorder services worldwide and need to be addressed in order to move the field forward. We provide a number of solutions and research areas that need greater focus so that we are able to improve the efficacy of eating disorder treatment services.

Autonomic nervous system function in women with anorexia nervosa.

PURPOSE: Abnormalities in autonomic function have been observed in people with anorexia nervosa. However, the majority of investigations have utilised heart rate variability as the sole assessment of autonomic activity. The current study utilised a variety of methodologies to assess autonomic nervous system function in women with a current diagnosis of anorexia, a past diagnosis of anorexia who were weight-restored, and healthy controls. METHODS: The sample included 37 participants: 10 participants with anorexia, 17 weight-restored participants (minimum body mass index > 18.5 for minimum of 12 months) and 10 controls. Assessments of autonomic function included muscle sympathetic nerve activity (MSNA) using microneurography, heart rate variability, baroreflex sensitivity, blood pressure variability, head-up tilt table test, sudomotor function and assessment of plasma catecholamines. RESULTS: MSNA (bursts/min) was significantly decreased in both anorexia (10.22 ± 6.24) and weight-restored (17.58 ± 1.68) groups, as compared to controls (23.62 ± 1.01, p < 0.001 and p = 0.033, respectively). Participants with anorexia had a significantly lower standard deviation in heart rate, lower blood pressure variability and decreased sudomotor function as compared to controls. Weight-restored participants demonstrated decreased baroreflex sensitivity in response to head-up tilt as compared to controls. CONCLUSION: Women with a current or previous diagnosis of anorexia have significantly decreased sympathetic activity, which may reflect a physiological response to decreased energy intake. During the state of starvation, women with anorexia also displayed decreased sudomotor function. The consequences of a sustained decrease in MSNA are unknown, and future studies should investigate autonomic function in long-term weight-restored participants to determine whether activity returns to normal.

A biomarker and endophenotype for anorexia nervosa?

OBJECTIVE: Recent research has suggested that a type of atypical eye movement, called square wave jerks, together with anxiety, may distinguish individuals with anorexia nervosa from those without anorexia nervosa and may represent a biomarker and endophenotype for the illness. The aim of this study was to identify the presence of this proposed marker in individuals currently with anorexia nervosa relative to healthy controls, and to identify the state independence and heritability of this putative marker by exploring whether it also exists in individuals who are weight-restored from anorexia nervosa and first-degree relatives (i.e. sisters of people with anorexia nervosa). METHODS: Data from 80 female participants (20/group: current anorexia nervosa, weight-restored from anorexia nervosa, sisters of people with anorexia nervosa and healthy controls) were analysed. Square wave jerk rate was acquired during a fixation task, and anxiety was measured with the State Trait Anxiety Inventory. RESULTS: Current anorexia nervosa, weight-restored from anorexia nervosa and sisters of people with anorexia nervosa groups made significantly more square wave jerks than healthy controls, but did not differ from one another. Square wave jerk rate and anxiety were found to discriminate groups with exceptionally high accuracy (current anorexia nervosa vs healthy control = 92.5%; weight-restored from anorexia nervosa vs healthy control = 77.5%; sisters of people with anorexia nervosa vs healthy control = 77.5%; p < .001). CONCLUSION: The combination of square wave jerk rate and anxiety was found to be a promising two-element marker for anorexia nervosa, and has the potential to be used as a biomarker or endophenotype to identify people at risk of anorexia nervosa and inform future treatments.

Valuing the voice of lived experience of eating disorders in the research process: Benefits and considerations.

Although the inclusion of individuals with lived experience is encouraged within the research process, there remains inconsistent direct involvement in many mental health fields. Within the eating disorders field specifically, there is a very strong and increasing presence of lived experience advocacy. However, due to a number of potential challenges, research undertaken in consultation or in collaboration with individuals with lived experience of an eating disorder is scarce. This paper describes the significant benefits of the inclusion of individuals with lived experience in research. The specific challenges and barriers faced in eating disorders research are also outlined. It is concluded that in addition to existing guidelines on working with lived experience collaborators in mental health research, more specific procedures are required when working with those with eating disorders.

Understanding self-report and neurocognitive assessments of cognitive flexibility in people with and without lifetime anorexia nervosa.

Objective: Anorexia nervosa (AN) is a serious eating disorder associated with several cognitive difficulties including poor cognitive flexibility (i.e. difficulties in effectively adapting to changes in the environment and/or changing task demands). AN research has primarily assessed cognitive flexibility using neurocognitive tests, and little is known about the differences or similarities between self-report and neurocognitive assessments of cognitive flexibility. This study investigated the relationship between self-report and neurocognitive assessments of cognitive flexibility in people with no history of an eating disorder (n = 207) and people with a self-reported lifetime diagnosis of AN (n = 19).Methods: Participants completed self-report and neurocognitive assessments of cognitive flexibility through an online study.Results: No significant correlations were found between self-report and neurocognitive assessments of cognitive flexibility for either group of the sample, suggesting that these assessments may evaluate different aspects of cognitive flexibility. Further, negative mood and self-reported eating disorder symptoms were found to significantly relate to self-reported cognitive flexibility, but were not associated with performance on neurocognitive tests of cognitive flexibility.Conclusions: To provide a comprehensive understanding of perceived and objective cognitive flexibility in AN, future research and clinical assessments should include both self-report and neurocognitive assessments.

Anorexia nervosa, weight restoration and biological siblings: Differences and similarities in clinical characteristics.

OBJECTIVE: Anorexia nervosa (AN) is associated with clinical characteristics including eating disorder symptomatology, negative mood states, perfectionism and cognitive inflexibility. Whether these characteristics differ across illness stages, and are also present in first-degree relatives, demonstrating heritability, is unclear. The aim of this research was to compare current AN (c-AN), weight-restored AN (wr-AN), sisters of individuals with AN (AN-sis) and healthy controls (HC) on these measures. METHOD: Eighty participants (n = 20/group) completed the study. RESULTS: Eating disorder symptomatology was similar among c-AN and wr-AN groups, whereas the AN-sis did not differ from either wr-AN or HC. Anxiety was significantly higher in c-AN, wr-AN and AN-sis groups, relative to HC. Increased perfectionism was identified in the c-AN and wr-AN groups compared to AN-sis and HC on the 'concern over mistakes', 'personal standards' and 'doubt and actions' subscales of the Multidimensional Perfectionism Scale. Group differences were not apparent on cognitive flexibility. CONCLUSIONS: These findings suggest that anxiety may be a risk factor or linked to genetic susceptibility for AN, as well as specific aspects of perfectionism that relate to self-imposed standards.

The contribution of sleep to anorexia nervosa severity.

PURPOSE: Anorexia nervosa (AN) is associated with poor sleep and altered circadian rhythms. Evidence is unclear as to whether these features relate to ongoing psychiatric symptoms of AN, or are merely concomitant with low weight. In this study, we sought to evaluate subjective sleep quality and sleep-wake preferences in a sample of individuals with lifetime AN. Furthermore, we aimed to examine whether sleep quality would significantly predict AN symptom severity, after accounting for demographic features and negative emotions (depression, anxiety and stress). METHODS: Adults with a lifetime diagnosis of AN (n = 96) or no lifetime psychiatric diagnoses (NC; n = 246) completed an online survey assessing demographics, sleep quality, circadian sleep-wake preferences, eating disorder symptoms, and negative emotions. RESULTS: AN participants reported significantly poorer sleep quality overall, including increased sleep disturbances, use of sleep medications, and daytime dysfunction, as compared to NC participants. Groups did not differ significantly in circadian sleep-wake preferences. Regression analysis showed that among AN participants, sleep quality and negative emotions significantly predicted AN symptom severity, while sex and body mass index (BMI) did not. CONCLUSION: The findings demonstrate that poor sleep quality was associated with more severe symptoms of AN, even when accounting for negative emotions and BMI. Future research should investigate causal interactions between sleep quality and AN symptom severity longitudinally and across different recovery stages. LEVEL OF EVIDENCE: Level III-Cohort and case-control analytic studies.

Depression, perceived disability and unemployment are associated with reduced life satisfaction in anorexia nervosa.

Life satisfaction is a core aspect of an individual's wellbeing and describes the subjective assessment of their quality of life. Reduced life satisfaction is frequently reported in anorexia nervosa (AN),  but the factors contributing to this are still unclear. This study sought to extend previous work by examining 12 potential correlates of AN life satisfaction. One hundred and five female AN patients were administered questionnaires assessing life satisfaction, depression, anxiety, stress, employment status, marital status, body mass index, eating disorder symptomatology, perceived disability and readiness for change. A stepwise linear regression revealed that only depression, perceived disability and employment status were significantly associated with AN life satisfaction. The findings thus highlight prevailing mood and personal functioning as critical foci for clinical management strategies in people with AN. Addressing depressive symptoms and perceived disability while bettering employment prospects could facilitate improved AN life satisfaction.

The Relationship between Negative Symptoms and Both Emotion Management and Non-social Cognition in Schizophrenia Spectrum Disorders.

OBJECTIVE: There is ongoing debate regarding the relationship between clinical symptoms and cognition in schizophrenia spectrum disorders (SSD). The present study aimed to explore the potential relationships between symptoms, with an emphasis on negative symptoms, and social and non-social cognition. METHOD: Hierarchical cluster analysis with k-means optimisation was conducted to characterise clinical subgroups using the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms in n = 130 SSD participants. Emergent clusters were compared on the MATRICS Consensus Cognitive Battery, which measures non-social cognition and emotion management as well as demographic and clinical variables. Spearman's correlations were then used to investigate potential relationships between specific negative symptoms and emotion management and non-social cognition. RESULTS: Four distinct clinical subgroups were identified: 1. high hallucinations, 2. mixed symptoms, 3. high negative symptoms, and 4. relatively asymptomatic. The high negative symptom subgroup was found to have significantly poorer emotion management than the high hallucination and relatively asymptomatic subgroups. No further differences between subgroups were observed. Correlation analyses revealed avolition-apathy and anhedonia-asociality were negatively correlated with emotion management, but not non-social cognition. Affective flattening and alogia were not associated with either emotion management or non-social cognition. CONCLUSIONS: The present study identified associations between negative symptoms and emotion management within social cognition, but no domains of non-social cognition. This relationship may be specific to motivation, anhedonia and apathy, but not expressive deficits. This suggests that targeted interventions for social cognition may also result in parallel improvement in some specific negative symptoms.

Characteristics of people on long-acting injectable antipsychotics in Australia: Data from the 2010 National Survey of High Impact Psychosis.

OBJECTIVE: This study investigates (1) the proportion of people with psychosis who are on long-acting injectable antipsychotics; (2) the difference in the demographic, clinical, substance use and adverse drug reaction profiles of people taking long-acting injectables compared to oral antipsychotics; and (3) the differences in the same profiles of those on first-generation antipsychotic versus second-generation antipsychotic long-acting injectables. METHODS: Data were collected as part of the Survey of High Impact Psychosis. For this study, participants with diagnoses of schizophrenia or schizoaffective disorder who were on any antipsychotic medication were included (N = 1049). RESULTS: Nearly a third (31.5%) of people with psychosis were on long-acting injectables, of whom 49.7% were on first-generation antipsychotic long-acting injectables and 47.9% were on second-generation antipsychotic long-acting injectables. This contrasts with oral antipsychotics where there was a higher utilisation of second-generation antipsychotics (86.3%). Of note, compared to those on the oral formulation, people on long-acting injectables were almost four times more likely to be under a community treatment order. Furthermore, people on long-acting injectables were more likely to have a longer duration of illness, reduced degree of insight, increased cognitive impairment as well as poor personal and social functioning. They also reported more adverse drug reactions. Compared to those on first-generation antipsychotic long-acting injectables, people on SGA long-acting injectables were younger and had had a shorter duration of illness. They were also more likely to experience dizziness and increased weight, but less likely to experience muscle stiffness or tenseness. CONCLUSION: Long-acting injectable use in Australia is associated with higher rates of community treatment order use, as well as poorer insight, personal and social performance, and greater cognitive impairment. While long-acting injectables may have the potential to improve the prognosis of people with psychosis, a better understanding of the choices behind the utilisation of long-acting injectable treatment in Australia is urgently needed.

Considerations for using the Wisconsin Card Sorting Test to assess cognitive flexibility.

The Wisconsin Card Sorting Test (WCST) is a popular neurocognitive task used to assess cognitive flexibility, and aspects of executive functioning more broadly, in research and clinical practice. Despite its widespread use and the development of an updated WCST manual in 1993, confusion remains in the literature about how to score the WCST, and importantly, how to interpret the outcome variables as indicators of cognitive flexibility. This critical review provides an overview of the changes in the WCST, how existing scoring methods of the task differ, the key terminology and how these relate to the assessment of cognitive flexibility, and issues with the use of the WCST across the literature. In particular, this review focuses on the confusion between the terms 'perseverative responses' and 'perseverative errors' and the inconsistent scoring of these variables. To our knowledge, this critical review is the first of its kind to focus on the inherent issues surrounding the WCST when used as an assessment of cognitive flexibility. We provide recommendations to overcome these and other issues when using the WCST in future research and clinical practice.