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.

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.

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.

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.

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.

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.

The Effects of Music-Based Interventions for Pain and Anxiety Management during Vaginal Labour and Caesarean Delivery: A Systematic Review and Narrative Synthesis of Randomised Controlled Trials.

Music-based interventions are not physically invasive, they usually have minimal side effects, and they are increasingly being implemented during the birthing process for pain and anxiety relief. The aim of this systematic review is to summarise and evaluate published, randomised controlled trials (RCTs) assessing the effects of music-based interventions for pain and anxiety management during vaginal labour and caesarean delivery. Following the PRISMA guidelines, a systematic search of the literature was conducted using: PsychInfo (Ovid), PubMed, and Web of Science. Studies were included in the review if they were RCTs that assessed the effects of music on pain and anxiety during vaginal and caesarean delivery by human mothers. A narrative synthesis was conducted on 28 identified studies with a total of 2835 participants. Most, but not all, of the included studies assessing music-based interventions resulted in reduced anxiety and pain during vaginal and caesarean delivery. Music as part of a comprehensive treatment strategy, participant-selected music, music coupled with another therapy, and relaxing/instrumental music was specifically useful for reducing light to moderate pain and anxiety. Music-based interventions show promising effects in mitigating pain and anxiety in women during labour. However, the long-term effects of these interventions are unclear.

The effect of a low-calorie diet on depressive symptoms in individuals with overweight or obesity: a systematic review and meta-analysis of interventional studies.

BACKGROUND: Individuals with overweight or obesity are at a high risk for so-called 'atypical' or immunometabolic depression, with associated neurovegetative symptoms including overeating, fatigue, weight gain, and a poor metabolic profile evidenced e.g. by dyslipidemia or hyperglycemia. Research has generated preliminary evidence for a low-calorie diet (LCD) in reducing depressive symptoms. The aim of the current systematic review and meta-analysis is to examine this evidence to determine whether a LCD reduces depressive symptoms in people with overweight or obesity. METHODS: Eligible studies were identified through PubMed, ISI Web of Science, and PsycINFO until August 2023. Standardized mean differences (SMDs) were derived using random-effects meta-analyses for (1) pre-post LCD comparisons of depression outcomes, and (2) LCD v. no-diet-control group comparisons of depression outcomes. RESULTS: A total of 25 studies were included in the pre-post meta-analysis, finding that depression scores were significantly lower following a LCD (SMD = -0.47), which was not significantly moderated by the addition of exercise or behavioral therapy as a non-diet adjunct. Meta-regressions indicated that a higher baseline BMI and greater weight reduction were associated with a greater reduction in depression scores. The intervention-control meta-analysis (n = 4) found that overweight or obese participants adhering to a LCD showed a nominally lower depression score compared with those given no intervention (SMD = -0.29). CONCLUSIONS: There is evidence that LCDs may reduce depressive symptoms in people with overweight or obesity in the short term. Future well-controlled intervention studies, including a non-active control group, and longer-term follow-ups, are warranted in order to make more definitive conclusions.

Randomized Controlled Trials to Treat Obesity in Military Populations: A Systematic Review and Meta-Analysis.

In recent years, overweight and obesity have reached an alarmingly high incidence and prevalence worldwide; they have also been steadily increasing in military populations. Military personnel, as an occupational group, are often exposed to stressful and harmful environments that represent a risk factor for disordered eating, with major repercussions on both physical and mental health. This study aims to explore the effectiveness of weight loss interventions and assess the significance of current obesity treatments for these populations. Three online databases (PubMed, PsycInfo, and Web of Science) were screened to identify randomized controlled trials (RCTs) aiming to treat obesity in active-duty military personnel and veterans. Random-effects meta-analyses were conducted for body weight (BW) and body mass index (BMI) values, both longitudinally comparing treatment groups from pre-to-post intervention and cross-sectionally comparing the treatment group to controls at the end of the intervention. A total of 21 studies were included: 16 cross-sectional (BW: n = 15; BMI: n = 12) and 16 longitudinal (BW: n = 15; BMI: n = 12) studies were meta-analyzed, and 5 studies were narratively synthesized. A significant small overall BW and BMI reduction from baseline to post-intervention was observed (BW: g = -0.10; p = 0.015; BMI: g = -0.32; p < 0.001), together with a decreased BMI (g = -0.16; p = 0.001) and nominally lower BW (g = -0.08; p = 0.178) in the intervention group compared to controls at the post-intervention time-point. Despite limitations, such as the heterogeneity across the included interventions and the follow-up duration, our findings highlight how current weight loss interventions are effective in terms of BW and BMI reductions in military populations and how a comprehensive approach with multiple therapeutic goals should be taken during the intervention.

Exploring Correlations of Food-Specific Disgust with Eating Disorder Psychopathology and Food Interaction: A Preliminary Study Using Virtual Reality.

The emotion of disgust is thought to play a critical role in maintaining restrictive eating among individuals with anorexia nervosa. This exploratory cross-sectional study examined correlations between food-specific trait and state disgust, eating disorder psychopathology, illness severity (body mass index: BMI), and interactions with virtual foods in people with anorexia nervosa. Food-specific trait disgust and eating disorder symptoms were measured before exposure to virtual foods in one of three virtual reality (VR) kitchens to which participants were randomly allocated. Food interactions (eye gaze and reaching towards virtual foods) were measured during the VR exposure. Food-specific state disgust ratings were collected after the VR exposure. In the entire sample, eating disorder symptoms correlated positively with food-specific trait disgust (rs (68) = 0.45, p < 0.001). We also found a significant association between food-specific state disgust and eating disorder symptoms in each virtual kitchen scenario: virtual kitchen only (rs (22) = 0.40, p = 0.05), virtual kitchen plus pet (rs (22) = 0.80, p < 0.001), and virtual kitchen plus avatar (rs (20) = 0.78, p < 0.001). No significant correlation was observed for the link between food-specific disgust measures and food-related touch. Correlations between food-specific trait disgust and food-related eye gaze differed across scenarios. The current experimental paradigm needs to be improved to draw firm conclusions. Both food-specific trait and state disgust are associated with eating disorder psychopathology, and therefore, effective strategies are warranted to attenuate food-specific disgust.

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.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders.

OBJECTIVES: This 2023 update of the WFSBP guidelines for the pharmacological treatment of eating disorders (EDs) reflects the latest diagnostic and psychopharmacological progress and the improved WFSBP recommendations for the assessment of the level of evidence (LoE) and the grade of recommendation (GoR). METHODS: The WFSBP Task Force EDs reviewed the relevant literature and provided a timely grading of the LoE and the GoR. RESULTS: In anorexia nervosa (AN), only a limited recommendation (LoE: A; GoR: 2) for olanzapine can be given, because the available evidence is restricted to weight gain, and its effect on psychopathology is less clear. In bulimia nervosa (BN), the current literature prompts a recommendation for fluoxetine (LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1). In binge-eating disorder (BED), lisdexamfetamine (LDX; LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1) can be recommended. There is only sparse evidence for the drug treatment of avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD). CONCLUSION: In BN, fluoxetine, and topiramate, and in BED, LDX and topiramate can be recommended. Despite the published evidence, olanzapine and topiramate have not received marketing authorisation for use in EDs from any medicine regulatory agency.

Case report: Intramuscular ketamine or intranasal esketamine as a treatment in four patients with major depressive disorder and comorbid anorexia nervosa.

Introduction: A comorbid diagnosis of a depressive disorder is a negative prognostic factor for individuals with AN, and novel treatments are needed to target depressive symptoms in this population. One emerging promising treatment for depressive disorders is ketamine, although there is less research investigating the use of ketamine for alleviating depression in people with AN. Case report: This study reports on four patients with a lifetime diagnosis of AN and a comorbid diagnosis of major depressive disorder who received either intramuscular ketamine (n = 2) or intranasal esketamine (n = 2) treatment from a private psychiatric clinic. Depressive symptomatology (PHQ-9) was measured prior to (es)ketamine administration on every dosing session and adverse effects were recorded during and after dosing. All patients reported a subjective decrease in depression, although only those administered intranasal esketamine showed a reduction in PHQ-9 depression scores over time. Number of doses ranged from 3 to 23. All patients tolerated treatment well and no serious adverse effects emerged, however nausea/vomiting was experienced by one patient on one dosing session. Weight remained stable in all cases, although notably across all patients, weight at the beginning of treatment was within a "healthy" range. Discussion: These findings suggest that (es)ketamine may reduce depressive symptoms in people with major depressive disorder and a comorbid diagnosis of AN. Future feasibility and pilot trials are warranted in order to elicit robust data on efficacy, acceptability, safety and tolerability.

Autopsy of a failed trial part 1: A qualitative investigation of clinician's views on and experiences of the implementation of the DAISIES trial in UK-based intensive eating disorder services.

OBJECTIVE: The DAISIES trial, comparing inpatient and stepped-care day patient treatment for adults with severe anorexia nervosa was prematurely terminated in March 2022 due to poor recruitment. This qualitative study seeks to understand the difficulties faced during the trial by investigating stakeholders' views on and experiences of its implementation. METHOD: Semi-structured interview and focus group transcripts, and trial management and oversight group meeting minutes from May 2020-June 2022 were analysed using thematic analysis. Participants were 47 clinicians and co-investigators involved with the DAISIES trial. The Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework was applied to the interpretive themes to classify barriers and facilitators to implementation. RESULTS: Five themes were identified: incompatible participation interests; changing standard practice; concerns around clinical management; systemic capacity and capability issues; and Covid-19 disrupting implementation. Applying the NASSS framework indicated the greatest implementation challenges to arise with the adopters (e.g. patients, clinicians), the organisational systems (e.g. service capacity), and the wider socio-political context (e.g. Covid-19 closing services). CONCLUSIONS: Our findings emphasise the top-down impact of systemic-level research implementation challenges. The impact of the Covid-19 pandemic accentuated pre-existing organisational barriers to trial implementation within intensive eating disorder services, further limiting the capacity for research.

Eating cognitions, emotions and behaviour under treatment with second generation antipsychotics: A systematic review and meta-analysis.

Weight gain and metabolic disturbances are frequent in people treated with second generation antipsychotics (SGA). We aimed to investigate the effect of SGAs on eating behaviors, cognitions and emotions, as a possible contributor to this adverse effect. A systematic review and a meta-analysis were conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Original articles measuring outcomes relating to eating cognitions, behaviours and emotions, during treatment with SGAs were included in this review. A total of 92 papers with 11,274 participants were included from three scientific databases (PubMed, Web of Science and PsycInfo). Results were synthesized descriptively except for the continuous data where meta-analyses were performed and for the binary data where odds ratios were calculated. Hunger was increased in participants treated with SGAs with an odds ratio for appetite increase of 1.51 (95% CI [1.04, 1.97]; z = 6.40; p < 0.001). Compared to controls, our results showed that craving for fat and carbohydrates are the highest among other craving subscales. There was a small increase in dietary disinhibition (SMD = 0.40) and restrained eating (SMD = 0.43) in participants treated with SGAs compared to controls and substantial heterogeneity across studies reporting these eating traits. There were few studies examining other eating-related outcomes such as food addiction, satiety, fullness, caloric intake and dietary quality and habits. Understanding the mechanisms associated with appetite and eating-related psychopathology changes in patients treated with antipsychotics is needed to reliably inform the development of effective preventative strategies.