Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol.

BACKGROUND: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. METHODS: STORY follows 720 young people aged 16-25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Oura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. DISCUSSION: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

A randomised controlled feasibility trial of intermittent theta burst stimulation with an open longer-term follow-up for young people with persistent anorexia nervosa (RaISE): Study protocol.

OBJECTIVE: We present the protocol of a feasibility randomised controlled trial (RCT) of intermittent theta burst stimulation (iTBS) for young people with anorexia nervosa (AN). Effective first-line psychological therapies exist for young people with AN, but little is known about how to treat those who do not respond. Non-invasive neuromodulation, such as iTBS, could address unmet treatment needs by targeting neurocircuitry associated with the development and/or maintenance of AN. DESIGN: Sixty-six young people (aged 13-30 years) with persistent AN will be randomly allocated to receive 20 sessions of real or sham iTBS over the left dorsolateral prefrontal cortex in addition to their usual treatment. Outcomes will be measured at baseline, post-treatment (1-month post-randomisation) and 4-months post-randomisation (when unblinding will occur). Additional open follow-ups will be conducted at 12- and 24-months post-randomisation. The primary feasibility outcome is the proportion of participants retained in the study at 4-months. Secondary outcomes include AN symptomatology, other psychopathology, quality of life, service utilisation, neurocognitive processes, and neuroimaging measures. DISCUSSION: Findings will inform the development of a future large-scale RCT. They will also provide exploratory data on treatment efficacy, and neural and neurocognitive predictors and correlates of treatment response to iTBS in AN.

Novel treatments for anorexia nervosa: Insights from neuroplasticity research.

OBJECTIVE: Treatment for anorexia nervosa (AN) remains challenging; there are no approved psychopharmacological interventions and psychotherapeutic strategies have variable efficacy. The investigation of evidence-based treatments has so far been compounded by an underdeveloped understanding into the neurobiological changes associated with the acute stages of AN. There is converging evidence of deficiencies in neuroplasticity in AN. METHOD: This paper provides an overview of neuroimaging, neuropsychological, molecular and qualitative findings relating to neuroplasticity in AN, translating these findings to the identification of novel biological and psychotherapeutic strategies. RESULTS: Novel psychopharmacological approaches that may ameliorate deficiencies in neuroplasticity include medications such as ketamine, psilocybin and human recombinant leptin. Anti-inflammatory medications and brain-derived neurotrophic factor mimetics may emerge as potential treatments following further research. Psychotherapeutic strategies that may target neuroplastic deficiencies, as well as having wider effects on identity, include imagery rescripting, memory specificity training, cognitive remediation therapy, exposure therapies, narrative therapies, cultural interventions (e.g. music and arts therapies) and yoga/mindfulness-based interventions. CONCLUSIONS: Treatments specifically targeted towards mitigating the neurobiological sequalae of AN are warranted, and emerging neurobiological and neuropsychological research utilising longitudinal designs and large sample sizes, as well as initial feasibility studies, are necessitated to bolster translational efforts.

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank.

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

A major role for common genetic variation in anxiety disorders.

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (ncase = 25 453, ncontrol = 58 113) and an additional analysis of Current Anxiety Symptoms (ncase = 19 012, ncontrol = 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant positive genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.

Perspectives on psychedelic treatment and research in eating disorders: a web-based questionnaire study of people with eating disorders.

Approximately 1.25 million people in the UK suffer from an eating disorder, yet the treatment options show limited efficacy, warranting the need for novel approaches. This study aimed to investigate the perspectives of people with eating disorders on the use of complementary therapies and psychedelic research and treatment. Two hundred participants with eating disorders took part in this web survey study. The majority of participants (70%) had used a complementary treatment to manage their eating disorder. Participants believed that psychedelic research was worthwhile in the context of a moderate level of concern. The most popular solutions to meet these concerns included providing education around psychedelics and their effects and use in psychiatry and experiencing endorsement from professionals in the area. Moreover, participant responses emphasized the need for a safe, monitored environment and the patient-therapist rapport in the context of psychedelic treatment. The findings are explored concerning future trials of psychedelics as a treatment for eating disorders.

Length of stay for anorexia nervosa: Systematic review and meta-analysis.

OBJECTIVE: Evidence regarding global trends in length of stay for patients with anorexia nervosa is limited. The aim of this study is to conduct a meta-analysis examining the length of stay for anorexia nervosa patients globally, and to investigate moderators of the variance. METHOD: Medline, EMBASE and PsycINFO were searched for studies published up to January 2019. Two independent reviewers assessed the eligibility of each report based on predefined inclusion criteria. A meta-analysis was performed to calculate a pooled mean length of stay using the random-effects model. Subgroup analyses and meta-regression were conducted to explore potential sources of heterogeneity between studies. RESULTS: Of 305 abstracts reviewed, 71 studies met the inclusion criteria, generating 111 datasets. The pooled mean length of stay (95% confidence interval) was 76.3 days (73.3, 79.4) using the random-effects model, with marked variation across countries and time. Heterogeneity between studies was explained by age and admission body mass index. CONCLUSIONS: This meta-analysis found that although clinical features do contribute to length of admissions for anorexia nervosa, there are also global and temporal variations. Future research should provide an in-depth analysis of why and how this variation exists and what the impact is on the well-being of people with anorexia nervosa.

Common etiological architecture underlying reward responsiveness, externally driven eating behaviors, and BMI in childhood: findings from the Gemini twin cohort.

BACKGROUND: Studies have reported that impulsivity predicts childhood BMI and that the association is mediated by eating behaviors. One aspect of impulsivity-potentially crucial in the obesity context-is reward responsiveness, which may predispose to responsiveness to palatable food cues. The behavioral susceptibility theory hypothesizes that genetic susceptibility to obesity operates partly via genetically determined differences in appetite regulation. Reward responsiveness may therefore be one of the neuro-endophenotypes that mediates genetic susceptibility to obesity. OBJECTIVE: To test whether reward responsiveness, eating behaviors, and child BMI share common genetic architecture. METHODS: We examined reward responsiveness, eating behaviors, and BMI in 5-year-old children from Gemini, a UK birth cohort of 2402 twin pairs born in 2007. All measures were collected by parent report. Reward responsiveness was derived from the Behavioral Approach System. Compulsion to eat and eating for pleasure was measured with the "food responsiveness" scale of the Child Eating Behavior Questionnaire. Wanting to eat in response to environmental food cues was measured with the "external eating" scale of the Dutch Eating Behavior Questionnaire. Maximum-likelihood structural equation modeling was used to establish underlying common genetic and environmental influences. RESULTS: There were significant positive phenotypic correlations between all traits except for reward responsiveness and BMI. Genetic factors explained the majority of the association between food responsiveness and external eating (74%, 95% CI: 61, 87), whereas common shared environmental factors explained the majority of the associations between reward responsiveness with both food responsiveness (55%, 95% CI: 20, 90) and external eating (70%, 95% CI: 39, 100). CONCLUSIONS: Our study demonstrates the importance of common environmental factors in the shared etiology between reward responsiveness and childhood eating behaviors. However, the common etiology underlying both reward responsiveness and BMI is unclear, as there was no phenotypic correlation between reward responsiveness and BMI at this age. Further longitudinal research needs to detangle this complex relationship throughout development.

Genetic Overlap Between Type 2 Diabetes and Depression in a Sri Lankan Population Twin Sample.

OBJECTIVE: Results from twin studies examining the genetic overlap between type 2 diabetes and depression are currently inconclusive. This question has not been addressed in non-Western populations. We aimed to examine whether there are common genetic factors between type 2 diabetes and depression in a Sri Lankan population using genetic model-fitting analysis. METHOD: The Colombo Twin and Singleton Study-Phase 2 consists of 2019 singletons, and 842 monozygotic and 578 dizygotic twin pairs. The primary outcomes were self-reported type 2 diabetes diagnosis and Beck Depression Inventory scores. Standard bivariate twin models were fitted to estimate the genetic and environmental (co)variance of type 2 diabetes and depression. RESULTS: In the best-fitting model, the phenotypic correlation between type 2 diabetes and depression was significant in female individuals only (r = 0.15 [0.08-0.21]). This association was primarily attributed to a significant genetic correlation between the traits (rA = 0.53 [0.19-0.98]). CONCLUSIONS: In female individuals, but not male individuals, we found a significant genetic overlap between type 2 diabetes and depression in the context of a modest phenotypic correlation.

Task-sharing interventions for patients with anorexia nervosa or their carers: a systematic evaluation of the literature and meta-analysis of outcomes.

The eating disorder clinical and scientific community advocates for the use of a shared approach to healthcare that actively involves patients and carers. A systematic review of the literature on guided self-help or self-help in anorexia nervosa (targeting either the individual affected by the illness or their carers) and meta-analyses of studies using randomised controlled designs for the evaluation of the outcomes: (1) drop-out from end-of-treatment assessment, (2) body mass index (BMI), (3) anxiety, (4) depression and (5) quality of life, were undertaken. Guided self-help was directed to patients in 15 studies and to carers in seven studies. The interventions were based on a variety of theoretical models, used different formats (books and digital materials), and were delivered by individuals with a range of experiences and expertise (e.g. individuals with lived experience of the illness, graduate students, or clinically trained professionals). Guided self-help was associated with significantly lower drop-out from the completion of end-of-treatment assessments compared to a control condition. There was an improvement in carers' wellbeing from skill-sharing interventions. Guided self-help may facilitate patients' treatment engagement and also improve carers' wellbeing.

Evaluation of a novel transition support intervention in an adult eating disorders service: ECHOMANTRA.

Admissions and re-admissions for inpatient care for anorexia nervosa have been increasing. The aim of this study was to examine whether the transition from inpatient care to the community could be facilitated by supplementing usual treatment with ECHOMANTRA (transition interventions) for both patients and carers. A case series study was employed using a mixed-methods approach to measure the feasibility and efficacy of augmenting intensive hospital treatment with ECHOMANTRA. A consecutive series of consenting patients (n = 31) and carers (n = 21) were assessed on admission, discharge, and at 3 months follow-up. These outcomes were compared with audit data (n = 152) previously collected (2007-2017). The length of stay for the ECHOMANTRA intervention group was 4.5 weeks less than the comparison group, and weight gain was 0.11 kg per week higher. Improvements in patient symptomology were sustained at follow-up. Thematic analysis of the feedback from both patients and carers suggests that the intervention is valued. Carer burden was reduced and their skills improved (both moderate size changes). In conclusion, both the acceptability and efficiency of inpatient care for anorexia nervosa may be improved by augmenting treatment to prepare for transition from inpatient care by giving support to both patients and their carers.

An illustration of collaborative care with a focus on the role of fathers in Maudsley Anorexia Nervosa Treatment for Adults (MANTRA).

The aim of this case study is to illustrate the importance of collaborative care as part of Maudsley Anorexia Nervosa Treatment for Adults (MANTRA). Mothers are often at the foreground of providing support within the family. However, fathers have the potential to play a profound role. In this paper, we describe a patient with anorexia nervosa treated with the MANTRA. The formulation of this case included autistic spectrum traits in both the father and daughter leading to social isolation. We describe how the family members were engaged into treatment and how paternal support was used to promote social connection and an improved quality of life in the daughter. Some details of the case have been altered to maintain confidentiality.

A systematic review of studies on the faecal microbiota in anorexia nervosa: future research may need to include microbiota from the small intestine.

PURPOSE: Anorexia nervosa (AN) is a poorly understood and often chronic condition. Deviations in the gut microbiota have been reported to influence the gut-brain axis in other disorders. Therefore, if present in AN, it may impact on symptoms and illness progression. A review of the gut microbiota studies in AN is presented. METHOD: A literature search on PubMed yielded 27 articles; 14 were selected and based on relevance, 9 articles were included. The findings were interpreted in the larger context of preclinical research and clinical observations. RESULTS: 8 out of 9 included studies analysed microbiota from faeces samples, while the last analysed a protein in plasma produced by the gut. Two studies were longitudinal and included an intervention (i.e., weight restoration), five were cross-sectional, one was a case report, and the last was a case series consisting of three cases. Deviations in abundance, diversity, and microbial composition of the faecal microbiota in AN were found. CONCLUSION: There are currently only a few studies on the gut microbiota in AN, all done on faeces samples, and not all describe the microbiota at the species level extensively. The Archaeon Methanobrevibacter smithii was increased in participants with a BMI < 25 in one study and specifically in AN patients in three studies. Methanobrevibacter smithii may, if detected, be a benchmark biomarker for future studies. We propose that microbiota samples could also be collected from the small intestine, where a major exchange of nutrients takes place and where the microbiota may have a biological impact on AN.

How we developed a trainee-led book group as a supplementary education tool for psychiatric training in the 21st century.

BACKGROUND: Postgraduate medical education has, in recent years, become a dynamic field with the increasing availability of innovative and interactive teaching techniques. Anecdotal evidence suggests that the current focus of psychiatric training on the acquisition of scientific and clinical knowledge is inadequate to address the multidimensional nature of psychiatry. Supplementary teaching tools may be usefully applied to address this need. METHODS: A group of trainees at the Maudsley Hospital and Institute of Psychiatry (UK) pioneered the use of a book group as an innovative teaching tool to enhance the psychiatric training experience by, amongst other aspects, facilitating dialogue between peers on fundamental epistemological issues raised by critical engagement with seminal psychiatric texts. RESULTS: Feedback from members suggested that participation in the book group broadened the overall learning potential and experience of psychiatry. The key ingredients were identified as: (i) collaborative peer-to-peer learning; (ii) the use of 'flipped classroom' model; and (iii) joint ownership. CONCLUSION: The book group has demonstrated real potential to facilitate direct trainee engagement with the multi-faceted nature of psychiatry as a complex humanistic discipline within an informal learning space.

Meal support using mobile technology in Anorexia Nervosa. Contextual differences between inpatient and outpatient settings.

The aim of this study was to examine the impact of a "supported eating" intervention using mobile technology in patients with Anorexia Nervosa (AN). Twenty Inpatients and 18 Outpatients with AN underwent a test meal on two occasions, whilst listening to either a short video-clip ('vodcast'), or music delivered on an MP4 player. Self-report and behavioural measures were collected before and after each test meal. Differences were found between the inpatient and outpatient settings. Inpatients drank more of the test meal and had increased levels of vigilance to food after the test meal, in both conditions. When the support conditions (Vodcast vs. Music) were compared, inpatients seemed to benefit more from listening to music (reduced distress and more smoothie drunk), whereas outpatients benefitted more from using the vodcast (reduced distress, more smoothie drunk, and reduced vigilance to food). The context in which the intervention was delivered had an impact on self-report and behavioural measures collected during the test meal. This suggests that the form of meal support in AN needs to match the context.

Eating in eating disorders.

The aim of this paper is to bring eating back into the centre of the eating disorder discourse. The ability to interrogate and understand the central processes of appetite has increased considerably since the discovery of leptin and the ability to observe brain function with scanning methodologies. This has led to substantial progress in understanding the biological causative and maintaining factors in eating disorders, opening up the possibility of translating the latest findings into new forms of treatment. The biological mechanisms underpinning symptoms evolution and course of illness will first be described, follows by a discussion on integrating the research evidence in fear and feeding into patient care.

Reply to Skokou, M. Comment on "Keeler et al. Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review. Nutrients 2021, 13, 4158".

In response to our narrative review, which suggested the use of the glutamatergic n-methyl-D-aspartate (NMDA) receptor antagonist ketamine as a potential treatment for anorexia nervosa (AN) [...].