Longitudinal changes in brain-derived neurotrophic factor (BDNF) but not cytokines contribute to hippocampal recovery in anorexia nervosa above increases in body mass index.

BACKGROUND: Physical sequelae of anorexia nervosa (AN) include a marked reduction in whole brain volume and subcortical structures such as the hippocampus. Previous research has indicated aberrant levels of inflammatory markers and growth factors in AN, which in other populations have been shown to influence hippocampal integrity. METHODS: Here we investigated the influence of concentrations of two pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]) and brain-derived neurotrophic factor (BDNF) on the whole hippocampal volume, as well as the volumes of three regions (the hippocampal body, head, and tail) and 18 subfields bilaterally. Investigations occurred both cross-sectionally between acutely underweight adolescent/young adult females with AN (acAN; n = 82) and people recovered from AN (recAN; n = 20), each independently pairwise age-matched with healthy controls (HC), and longitudinally in acAN after partial renourishment (n = 58). Hippocampal subfield volumes were quantified using FreeSurfer. Concentrations of molecular factors were analyzed in linear models with hippocampal (subfield) volumes as the dependent variable. RESULTS: Cross-sectionally, there was no evidence for an association between IL-6, TNF-α, or BDNF and between-group differences in hippocampal subfield volumes. Longitudinally, increasing concentrations of BDNF were positively associated with longitudinal increases in bilateral global hippocampal volumes after controlling for age, age2, estimated total intracranial volume, and increases in body mass index (BMI). CONCLUSIONS: These findings suggest that increases in BDNF may contribute to global hippocampal recovery over and above increases in BMI during renourishment. Investigations into treatments targeted toward increasing BDNF in AN may be warranted.

Olanzapine for young PEople with aNorexia nervosa (OPEN): A protocol for an open-label feasibility study.

INTRODUCTION: Antipsychotics are routinely prescribed off-label for anorexia nervosa (AN) despite limited evidence. This article presents a protocol of a study aiming to assess the feasibility of a future definitive trial on olanzapine in young people with AN. METHODS AND ANALYSIS: In an open-label, one-armed feasibility study, 55 patients with AN or atypical AN, aged 12-24, receiving outpatient, inpatient or day-care treatment who are considered for olanzapine treatment will be recruited from NHS sites based in England. Assessments will be conducted at screening, baseline and at 8-, 16 weeks, 6- and 12 months. Primary feasibility parameters will be proportions of patients who agree to take olanzapine and who adhere to treatment and complete study assessments. Qualitative methods will be used to explore acceptability of the intervention and study design. Secondary feasibility parameters will be changes in body mass index, psychopathology, side effects, health-related quality of life, carer burden and proportion of participants who would enrol in a future randomised controlled trial. The study is funded by the National Institute for Health Research via Health Technology Assessment programme. DISCUSSION: Olanzapine for young PEople with aNorexia nervosa will inform a future randomised controlled trial on the efficacy and safety of prescribing olanzapine in young people with AN.

Autopsy of a failed trial part 2: Outcomes, challenges, and lessons learnt from the DAISIES trial.

OBJECTIVE: The relative merits of inpatient or day-treatment for adults with anorexia nervosa (AN) are unknown. The DAISIES trial aimed to establish the non-inferiority of a stepped-care day patient treatment (DPT) approach versus inpatient treatment as usual (IP-TAU) for improving body mass index (BMI) at 12 months in adults with AN. The trial was terminated due to poor recruitment. This paper presents outcomes and investigates the reasons behind the trial's failure. METHOD: Fifteen patients with AN (of 53 approached) participated and were followed-up to 6 or 12 months. Summary statistics were calculated due to low sample size, and qualitative data concerning treatment experiences were analysed using thematic analysis. RESULTS: At baseline, participants in both trial arms rated stepped-care DPT as more acceptable. At 12 months, participants' BMIs had increased in both trial arms. Qualitative analysis highlighted valued and challenging aspects of care across settings. Only 6/12 sites opened for recruitment. Among patients approached, the most common reason for declining participation was their treatment preference (n = 12/38). CONCLUSIONS: No conclusions can be drawn concerning the effectiveness of IP-TAU and stepped-care DPT, but the latter was perceived more positively. Patient-related, service-related and systemic factors (COVID-19) contributed to the trial's failure. Lessons learnt can inform future studies.

Body Image, Nutrition, and Mental Health.

Classical examples of disorders associated with body image disturbances are eating disorders (EDs) such as anorexia nervosa (AN) and bulimia nervosa (BN), as well as body dysmorphic disorder (BDD) [...].

Anorexia nervosa: diagnostic, therapeutic, and risk biomarkers in clinical practice.

In anorexia nervosa (AN), measurable biological parameters can inform the process of treating patients. Such biomarkers include established laboratory parameters as well as a range of potential future biomarkers, including genetic, metabolomic, microbiomic, endocrine, immunological, hematological, electrophysiological, and neuroimaging parameters. In this opinion article we discuss how these biomarkers can support diagnosic and therapeutic processes at specific steps during the AN treatment cycle, that is, the diagnosis, diagnostic specification, risk management, choice of therapy, therapy monitoring, and treatment review. History-taking, physical and neuropsychological examination, clinical observation, and judgment about treatment success by the patient, their carers, and members of the multidisciplinary team are essential to interpret laboratory and imaging data appropriately and to assess the full clinical picture.

Pharmacological Treatment of Binge Eating Disorder and Frequent Comorbid Diseases.

Binge eating disorder (BED) is the most common specific eating disorder (ED). It is frequently associated with attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder (BD), anxiety disorders, alcohol and nicotine use disorder, and obesity. The aim of this narrative review was to summarize the evidence for the pharmacological treatment of BED and its comorbid disorders. We recommend the ADHD medication lisdexamfetamine (LDX) and the antiepileptic and antimigraine drug topiramate for the pharmacological treatment of BED. However, only LDX is approved for the treatment of BED in some countries. Medications to treat diseases frequently comorbid with BED include atomoxetine and LDX for ADHD; citalopram, fluoxetine, sertraline, duloxetine, and venlafaxine for anxiety disorders and depression; aripiprazole for manic episodes of BD; lamotrigine, lirasidone and lumateperone for depressive episodes of BD; naltrexone for alcohol use disorder; bupropion for nicotine use disorder; and liraglutide, semaglutide, and the combination of bupropion and naltrexone for obesity. As obesity is a frequent health consequence of BED, weight gain-inducing medications, such as the atypical antipsychotics olanzapine or clozapine, the novel antidepressant mirtazapine and tricyclic antidepressants, and the mood stabilizer valproate should be avoided where possible. It is currently unclear whether the novel and promising glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptor agonists like tirzepatide and retatrutide help with BED and its comorbidities. However, these compounds have been reported to reduce binge eating in individuals with obesity or overweight.

Pharmacological Studies in Eating Disorders: A Historical Review.

Eating disorders (EDs) are serious mental health conditions characterised by impaired eating behaviours and nutrition as well as disturbed body image, entailing considerable mortality and morbidity. Psychopharmacological medication is an important component in the treatment of EDs. In this review, we performed a historic analysis of pharmacotherapeutic research in EDs based on the scientific studies included in the recently published World Federation of Societies for Biological Psychiatry (WFSBP) guidelines for ED treatment. This analysis focuses on early approaches and trends in the methods of clinical pharmacological research in EDs, for example, the sample sizes of randomised controlled trials (RCTs). We found the development of psychopharmacological treatments for EDs followed advancements in psychiatric pharmacotherapy. However, the application of RCTs to the study of pharmacotherapy for EDs may be an impediment as limited participant numbers and inadequate research funding impede generalisability and statistical power. Moreover, current medication usage often deviates from guideline recommendations. In conclusion, the RCT model may not effectively capture the complexities of ED treatment, and funding limitations hinder research activity. Novel genetically/biologically based treatments are warranted. A more comprehensive understanding of EDs and individualised approaches should guide research and drug development for improved treatment outcomes.

Incidence of mental disorders in soldiers deployed to Afghanistan who have or have not experienced a life-threatening military incident-a quasi-experimental cohort study.

Introduction: There is very good international research on deployment-related mental disorders in military personnel. The incidence rates show a very wide range. A new strategy is therefore proposed in order to achieve better standardization and thus better comparability of the studies. In addition to a non-deployed comparison group, we propose to compare deployed soldiers with and without critical military incidents during the deployment. This additional distinction makes it possible to differentiate between the influencing variables of actual threat and general deployment stress. Methods: N = 358 male combat soldiers deployed to Afghanistan were included in the study. Clinical interviews were conducted several days before deployment and after deployment. Of them, n = 80 soldiers suffered a life-threatening military incident during deployment, whereas 278 soldiers did not. Odds ratios (OR) were calculated for the groups with and without critical military incidents and the new onset for PTSD, anxiety disorders and depressive disorders. Results: When comparing both groups, we found significantly higher 1-year incidence rates in the group with critical military incidents: 6.4% vs. 1.1% (OR 6.2) for post-traumatic stress disorder (PTSD); 7.0% vs. 1.1% (OR 6.5) for depression; and 15.9% vs. 2.8% (OR 6.6) for anxiety disorders. The 1-year incidence rate of mental multimorbidity (PTSD with anxiety or depression) was 4.8% vs. 0.4% (OR 12.0). Discussion: These results indicate that life-threatening military incidents during military deployment are important to mental health. As the different threat levels of the various missions are taken into account, additional predictors could be determined more precisely in further research.

Impact of life-threatening military incidents during deployments abroad on the relationships between military personnel and their families.

Introduction: The influence of deployments on family relationships has hardly been investigated. Following a recently proposed new research strategy, military personnel with and without deployment-related life-threatening military incidents during deployment were compared. The hypothesis was that partner and family relationships of military personnel who experienced such an event would deteriorate more. Methods: This study included N = 255 military personnel who had a romantic partner (n = 78 of them had children) when deployed to Afghanistan. Of these, n = 68 military personnel experienced a deployment-related critical event during the deployment, n = 187 did not. Partnership quality was assessed using a semi-structured pre- and post-deployment interview. Results: The partner relationships of military personnel who experienced a deployment-related life-threatening military incident during deployment broke up significantly more often. The partner relationships of all military personnel deteriorated significantly, with greater deterioration after deployment in the group who faced such incidents. These results were independent of age, rank or number of previous deployments. In addition, there was a significant deterioration in the relationships between all military personnel and their children with greater deterioration after deployment in the group who faced such incidents. Conclusion: Life-threatening military incidents during a deployment abroad appear to have a considerable influence on the quality and stability of the partner and family relationships of military personnel. These findings can be used to inform the development of specific pre- and post-deployment measures and training.

Exploring Alcohol-Related Behaviours in an Adult Sample with Anorexia Nervosa and Those in Recovery.

While individuals with Bulimia Nervosa (BN) and Binge Eating Disorder (BED) often present with a higher rate of Alcohol Use Disorder (AUD) than the general population, it is unclear whether this extends to AN. This cross-sectional study examined differences in alcohol-related behaviours, measured using the Alcohol Use Identification Test (AUDIT), between AN participants (n = 58), recovered AN (rec-AN) participants (n = 25), and healthy controls (n = 57). Statistical models controlled for age and ethnicity. The relationship between alcohol-related behaviours with ED psychopathology and with depression was also assessed. The findings indicated that acute AN participants were not at greater risk of AUD than healthy controls. However, rec-AN participants displayed greater total audit scores than those with acute AN, and more alcohol-related behaviours than healthy controls. Acute AN participants consumed significantly less alcohol than both the healthy control group and rec-AN group. No associations were found between ED psychopathology and alcohol-related behaviours in the AN group or rec-AN. This highlights alcohol as a potential coping mechanism following AN recovery. Clinicians should consider assessments for AUD and targeted interventions aimed at encouraging healthy coping mechanisms in this group. Future studies should look at alcohol use as a moderating factor for AN recovery.