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Objective: The main characteristics of Anorexia Nervosa (AN) in adults are restriction of energy intake relative to requirements leading to significant weight loss, disturbed body image, and intense fear of becoming fat. Traumatic experiences (TE) have been reported as common, although less is known about the relationship with other symptoms in severe AN. We investigated the presence of TE, PTSD, and the relation between TE, eating disorder (ED) symptoms, and other symptoms in moderate to severe AN (n = 97) at admission to inpatient weight-restoration treatment. All patients were enrolled in the Prospective Longitudinal all-comer inclusion study on Eating Disorders (PROLED). Methods: TE were assessed using the Post-traumatic stress disorder checklist, Civilian version (PCL-C), and ED symptoms using the Eating Disorder Examination Questionnaire (EDE-Q); depressive symptoms were assessed using the Major Depression Inventory (MDI), and the presence of Post-traumatic Stress Disorder (PTSD) was diagnosed according to ICD-10 criteria. Results: The mean score on PCL-C was high (mean 44.6 SD 14.7), with 51% having a PCL-C score at or above 44 (n = 49, suggested cut-off for PTSD), although only one individual was clinically diagnosed with PTSD. There was a positive correlation between baseline scores of PCL-C and EDE-Q-global score (r = 0.43; p < 0.01) as well as of PCL-C and all EDE-Q subscores. None of the included patients were admitted for treatment of TE/PTSD during the first 8 weeks of treatment. Conclusions: In a group of patients with moderate to severe AN, TE were common, and scores were high, although only one had a diagnosis of PTSD. TE were related to ED symptoms at baseline, but this association diminished during the weight restoration treatment.

Objective: To investigate whether cognitive inflexibility could be identified using the Wisconsin Card Sorting Test (WCST) in patients with severe and extreme anorexia nervosa (AN) compared to healthy control participants (HCs). Method: We used the WCST to assess 34 patients with AN (mean age: 25.9 years, mean body mass index (BMI): 13.2 kg/m2) 3–7 days after admission to a specialized nutrition unit and 34 HCs. The Beck Depression Inventory II and the Eating Disorder Inventory 3 were distributed. Results: The patients displayed more perseveration than HCs controlled for age and years of education, with moderate effect sizes (perseverative responses (%): adjusted difference = −7.74, 95% CI: −14.29–(−1.20), p-value: 0.021; perseverative errors (%): adjusted difference = −6.01, 95% CI: −11.06–(−0.96), p-value: 0.020). There were no significant relationships between perseveration and depression, eating disorder symptoms, illness duration, or BMI. Discussion: Patients with severe and extreme AN demonstrated lower cognitive flexibility compared to HCs. Performance was not related to psychopathology or BMI. Patients with severe and extreme anorexia nervosa may not differ from less severe patients in cognitive flexibility performance. As this study exclusively focused on patients suffering from severe and extreme AN, potential correlations might be masked by a floor effect.

Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18F]FE-PE2I. Results: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and po

Objective: Anorexia nervosa (AN) is a severe mental disorder frequently associated with high scores of depressiveness. We examined the short-term effects of inpatient treatment on depressiveness and eating disorder (ED) psychopathology using the self-rating Major Depression Inventory (MDI) and Eating Disorder Examination questionnaire (EDEq) for patients with AN. Material: Forty-nine patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on EDs (PROLED), were observed over eight weeks with baseline psychometric measures, EDE-q at baseline and endpoint, and weekly MDI self-scoring. Methods: Apart from the weekly Body Mass Index (BMI) measurements, patients were assessed at baseline using the Eating Disorder Inventory (EDI) and the Symptom Check List 92 (SCL-92). Results: Inpatient treatment reduced MDI consistently over 8 weeks (Wilks Lambda = 0.59, F = 4.1, p < 0.01) and this reduction in MDI was positively correlated with a reduction in EDEq (r = 0.44; p < 0.01) during inpatient treatment. Baseline medication did not predict changes in MDI during the inpatient treatment. BMI increased from 14.9 (week 1) to 17.2 (week 8). Conclusions: Inpatient treatment of AN is associated with a reduction in depressiveness. This improvement in depressiveness scores correlates with an improvement in ED psychopathology but not with weight gain.

Motivation to change behavior is seen as an important factor in achieving a better treatment effect in patients with eating disorders (ED). The aim of this systematic review was to assess whether motivational interviewing (MI) and motivational enhancement therapy (MET) might (1) increase motivation to change behavior and (2) improve eating disorder psychopathology (EDP) and body mass index (BMI) in patients with ED. To investigate this, a literature search was conducted on 9 March 2021 on four scientific databases: Cochrane, Embase (Ovid), MEDLINE (PubMed), and PsycInfo (EBSCO). A total of 2647 publications were identified and following a rigorous stepwise procedure to assess titles and abstracts and, thereafter, full texts of relevant publications, 13 studies were included in the data extraction and analyses. A few individual studies (n = 5) found a significant increase in motivation, two a decrease in ED symptoms (n = 2), while none found an effect on BMI. However, the meta-analysis of each outcome found effect sizes near zero, thereby confirming the results of previous narrative reviews that have described a lack of effect of MET/MI on motivation in ED. Since the individual studies differ substantially in design, and the outcomes were inconsistently assessed with regards to instruments and duration, the effect of MET/MI on motivation for behavioral change, ED psychopathology, and BMI is still unclear.

Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were searched for literature published until 13 July 2021. All study designs were eligible for inclusion if they focused on predictors of relapse after weight normalization in AN. Individual study definitions of relapse were used, and in general, this was either a drop in BMI and/or reccurrence of AN symptoms. Results: The database search identified 11,507 publications, leaving 9511 publications after the removal of duplicates and after a review of abstracts and titles; 191 were selected for full-text review. Nineteen publications met the criteria and included 1398 AN patients and 39 healthy controls (HC) from adults and adolescents (ages range 11–73 years). The majority used a prospective observational study design (12 studies), a few used a retrospective observational design (6 studies), and only one was a non-randomized control trial (NRCT). Sample sizes ranged from 16 to 191 participants. BMI or measures of body fat and leptin levels at discharge were the strongest predictors of relapse with an approximate relapse rate of 50% at 12 months. Other predictors included signs of eating disorder psychopathology at discharge. Conclusions: BMI at the end of treatment is a predictor of relapse in AN, which is why treatment should target a BMI well above 20. Together with the time to relapse, these outcomes are important to include in the evaluation of current and novel treatments in AN and for benchmarking.

Clinical trials in neurodegenerative disorders have been associated with high rate of failures, while in oncology, the implementation of precision medicine and focus on genetically defined subtypes of disease and targets for drug development have seen an unprecedented success. With more than 20 genes associated with Parkinson's disease (PD), most of which are highly penetrant and often cause early onset or atypical signs and symptoms, and an increasing understanding of the associated pathophysiology culminating in dopaminergic neurodegeneration, applying the technologies and designs into the field of neurodegeneration seems a logical step. This review describes some of the methods used in oncology clinical trials and some attempts in Parkinson’s disease and the potential of further implementing genetics, biomarkers and smart clinical trial designs in this disease area.

Objective: Anorexia nervosa (AN) is characterized by weight loss, distorted body image with fear of becoming fat and associated with anxiety, especially in relation to food intake. Anxiety in relation to meals and weight restoration remains a major challenge in the treatment of AN. We examined the effects of inpatient weight restoration treatment on levels of post-meal anxiety using visual analogue scale (VAS) ratings in patients with AN. Materials: Thirty-two patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on Eating Disorders (PROLED) were followed over eight weeks with baseline psychometric measures and weekly VAS anxiety self-scoring. Methods: Apart from the weekly body mass index (BMI) and VAS, patients were characterized at baseline using the Eating Disorder Examination Questionnaire (EDE-Q), Eating Disorder Inventory (EDI), Symptom Check List 92 (SCL-92), Major Depression Inventory (MDI), and Autism Quotient (AQ). Results: The results showed a significant time effect, Wilks Lambda = 0.523, F = 3.12, p < 0.05 (power of 0.862), indicating a reduction in VAS scores of anxiety from baseline to week 8. There was no effect of baseline medication or scores of MDI on the results. BMI increased from a mean of 15.16 (week 1) to 17.35 (week 8). In comparison, patients dropping out after only three weeks (n = 31) also had a trend toward a reduction in VAS anxiety (ns). Conclusions: Inpatient weight restoration treatment is associated with a decrease in post-meal anxiety in AN, an effect that occurs early and becomes clinically significant in patients who stay in treatment.

Despite the fact that eating disorders (EDs) are conditions that are potentially life-threat-ening, many people decline treatment. The aim of this study was to investigate why women decline specialized ED treatment, including their viewpoints on treatment services. Eighteen semi-struc-tured qualitative interviews were conducted with women who had declined inpatient or outpatient specialized ED treatment. A thematic analysis revealed five main themes: (1) Disagreement on treatment needs, (2) rigid standard procedures, (3) failure to listen, (4) deprivation of identity, and (5) mistrust and fear. The women had declined ED treatment because they believed that treatment was only focused on nutritional rehabilitation and that it failed to address their self-identified needs. From their perspectives treatment was characterized by rigid standard procedures that could not be adapted to their individual situations and preferences. They felt that the therapists failed to listen to them, and they felt deprived of identity and reduced to an ED instead of a real person. This investigation is one of the first of its kind to provide clues as to how treatment could be moderated to better meet the needs of women who decline specialized ED treatment.

A better understanding of explanatory factors for disease-specific health-related quality of life (HRQoL) in anorexia nervosa (AN) could help direct treatment providers to aspects of the most relevance for patient wellbeing and recovery. We aimed to investigate whether factors associated with HRQoL are the same for women with AN and normal-weight controls. The participants in this study were women with AN recruited from specialized eating disorder centers in Denmark and healthy, normal-weight controls invited via online social media. Participants completed online questionnaires on medical history, disease-specific HRQoL (Eating Disorders Quality of Life Scale, EDQLS) and generic HRQoL (SF-36), eating disorder symptomatology, depression, psychological wellbeing, and work and social adjustment. Questionnaires were fully completed by 211 women with AN (median age 21.7 years) and 199 controls (median age 23.9 years). Women with AN had poorer scores on all measures, i.e., worse HRQoL, psychological health, and work/social functioning. Eating disorder symptomatology affected EDQLS score in both groups, but poorer HRQoL in women with AN was also significantly associated with worse scores on bulimia, maturity fears, depression, vitality, and with older age. The factors investigated together explained 79% of the variance in EDQLS score. Management of disordered self-assessment and thought processes may be of particular importance to women with AN. Greater emphasis on these aspects alongside weight gain could enhance patient-clinician alliance and contribute to better treatment outcomes.

BACKGROUND: Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by persistent failure to meet nutritional needs, absence of body image distortion and often low body weight. Weight restorative treatment in ARFID-adults is provided for as in Anorexia Nervosa (AN), while the effect is unknown. The aim was to compare weight gain between ARFID and restrictive subtype of AN (AN-R), including exploring impact of medical factors and psychopathology. METHODS: Individuals with ARFID (n = 7; all cases enrolled over 5 years) and AN-R (n = 80) were recruited from the Prospective Longitudinal All-comers inclusion study in Eating Disorders (PROLED) during 5 years. All underwent weight restorative inpatient treatment. Clinical characteristics at baseline and weekly weight gain were recorded and compared. RESULTS: There were no significant differences at baseline weight, nor in weight gain between groups. Anxiety was statistically significantly higher in AN-R at baseline. CONCLUSIONS: Although there were differences in several clinical measures at baseline (Autism Quotient, symptom checklist, mood scores and Morgan Russel Outcome Scale), only anxiety was higher in AN-R. No differences in weight gain were observed, although mean values indicate a faster weight gain in the ARFID group. Standard weight restorative treatment in this study in adults with ARFID has similar weight gaining effect as in AN-R.

Anorexia nervosa (AN) is a severe psychiatric condition associated with high mortality and chronicity. The hunt for state, trait, subtyping, and prognostic biomarkers is ongoing and the orexigenic hormone ghrelin and its different forms, acyl ghrelin and desacyl ghrelin, have been proposed to be increased in AN, especially in the restrictive subtype. A systematic literature search was performed using established databases up to 30 November 2020. Forty-nine studies met inclusion criteria for cross-sectional and longitudinal meta-analyses on total ghrelin, acyl ghrelin, and desacyl ghrelin. All forms of ghrelin were increased in the acute stage of anorexia nervosa during fasting compared to healthy controls. Previous notions on differences in ghrelin levels between AN subtypes were not supported by current data. In addition, a significant decrease in total ghrelin was observed pre-treatment to follow-up. However, total ghrelin levels at follow-up were still marginally elevated compared to healthy controls, whereas for acyl ghrelin, no overall effect of treatment was observed. Due to heterogeneity in follow-up designs and only few data on long-term recovered patients, longitudinal results should be interpreted with caution. While the first steps towards a biomarker in acute AN have been completed, the value of ghrelin as a potential indicator of treatment success or recovery status or its use in subtype differentiation are yet to be established.

Background Body image disturbance is central to both the understanding and treatment of anorexia nervosa (AN); however, the underlying psychological processes involved are still not well understood. One way towards a better understanding of these mechanisms may be to explore the sense of embodiment in these patients in an attempt at integrating the role of the body in our understanding of the development of self in AN. It is hypothesized that difficulties in affective experiences of embodiment is related to insecure attachment, deficits in mentalization and self-objectification. Methods Sixteen inpatients with AN were interviewed with the Mirror Interview (MI). In the interview, the individual is asked a set of questions related to thoughts and feelings about the body while standing in front of a full-length mirror. Furthermore, all patients were assessed with the Adult Attachment Interview, which was coded for both attachment and mentalization (operationalized by the Reflective Functioning scale; RF). Self-objectification was measured with the Objectified Body Consciousness Scale (OBCS). Results Results from a multiple regression analysis showed that Global MI scores were significantly associated with Coherence of mind as an indicator of attachment, RF and scores on the OBCS. Conclusions The study suggests that affective experiences of embodiment in patients with AN are associated with negative attachment representations, mentalizing impairments and objectified body consciousness.

BACKGROUND: Studies show that adult patients with anorexia nervosa display cognitive impairments. These impairments may be caused by illness-related circumstances such as low weight. However, the question is whether there is a cognitive adaptation to enduring undernutrition in anorexia nervosa. To our knowledge, cognitive performance has not been assessed previously in a patient with anorexia nervosa with a body mass index as low as 7.7 kg/m2. CASE PRESENTATION: We present the cognitive profile of a 35-year-old woman with severe and enduring anorexia nervosa who was diagnosed at the age of 10 years. She was assessed with a broad neuropsychological test battery three times during a year. Her body mass index was 8.4, 9.3, and 7.7 kg/m2, respectively. Her general memory performance was above the normal range and she performed well on verbal and design fluency tasks. Her working memory and processing speed were within the normal range. However, her results on cognitive flexibility tasks (set-shifting) were below the normal range. CONCLUSIONS: The case study suggests that it is possible to perform normally cognitively despite extreme and chronic malnutrition though set-shifting ability may be affected. This opens for discussion whether patients with anorexia nervosa can maintain neuropsychological performance in spite of extreme underweight and starvation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02502617. Registered 20 July 2015.

Rationale: The psychopathology of anorexia nervosa (AN) includes altered social cognition and information processing of fear and anxiety. Oxytocin, a neuromodulating hormone, may influence these functions and could be valuable for the treatment of AN. Objective: The current study aimed at reviewing the effect of intranasal oxytocin (IN-OT) on attentional bias (AB) and emotion recognition (ER) in AN. Methods: A systematic literature review was done for free-text and the MeSH-terms: anorexia nervosa, feeding and eating disorders, and oxytocin. Six publications, reporting from 4 unique clinical trials, were included in this review. A meta-analysis was conducted to examine the effects of IN-OT on AB towards food images and ER on healthy controls (HC) and patients with AN. Results: Overall, IN-OT did not influence AB towards food images (effect size = 0.20 [- 0.16, 0.57], p = 0.28) and had no effect on ER (effect size = - 0.01 [- 0.27, 0.26], p = 0.97) in patients with AN and healthy control (HC) subjects collectively. Assessing HC and AN separately in subgroup analyses did not show any significant effect on AB and ER in neither of the subgroups. All tests were done between 15 and 55 min post-administration of IN-OT, while peak concentration in the cerebrospinal fluid has been determined to be at 75 min. Conclusion: The current level of evidence is moderate showing no effect of IN-OT on AB or ER in AN. However, brain exposure may not have been sufficient which future studies with IN-OT need to ensure by considering dose and dose-to-task interval.

OBJECTIVE: Research suggests that a variety of biological and psychosocial factors are associated with the sexual health of women diagnosed with anorexia nervosa (AN). This systematic scoping review, conducted in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, synthesizes the current literature concerning sexual function and dysfunction in women with AN. METHOD: We searched PubMed, EMBASE, and PsychInfo for literature published until April 2020. All study designs were eligible for inclusion, providing they focused on sexual function and dysfunction in women with AN. Studies that only included outcomes related to gender identity or sexual orientation were excluded. RESULTS: N = 28 studies met criteria for inclusion in the review. All studies were conducted in Western countries and the majority employed either a cohort or cross-sectional design. Although measures of sexual function and dysfunction varied markedly across studies, most studies adopted a biopsychosocial framework. Libido may be linked to body mass index (BMI), while other aspects of sexual functioning and behavior might not be specifically associated with weight status. Limited data are available on evidence-based interventions. DISCUSSION: Sexual dysfunction in women with AN is common. Although some of the variance is explained by low BMI, associated physiological sequelae and other psychosocial factors are also involved. Sexual dysfunction is a relevant clinical problem and clinicians should sensitively incorporate questions related to sexual function into their eating disorder assessments. Future research, using more robust designs and validated outcome measures, is needed to better understand causal pathways between the biological and psychosocial correlates of AN and sexual dysfunction. Identifying predictors of sexual function and dysfunction in more diverse groups of people with AN will support the development of evidence-based therapies.

BACKGROUND: Anorexia nervosa (AN) is a serious mental illness with high rates of relapse and mortality. Psychiatric comorbidities are common but their impact on the prognosis is largely unknown. OBJECTIVE: The aim was to investigate the influence of psychiatric comorbidity on weight gain during treatment of AN. METHODS: A systematic search was performed in PubMed/MEDLINE, EMBASE and PsycINFO. Studies evaluating psychiatric comorbidity as a predictor for treatment outcome (weight gain) were included, however, comorbid alcohol/drug addiction was excluded from this review. RESULTS: Four thousand five hundred and twenty six publications were identified from which 15 were included. The majority of the included studies had a prospective open naturalistic study design, a short-term follow-up period, and were based on small populations of primarily adolescent and adult women. Four studies indicate depression, and two obsessiveness as negative prognostic factors, whilst one study indicated moderate depression and yet another, neuroticism, as positive predictors for weight gain. DISCUSSION: The systematic scoping review found a large number of publications whereof only a few directly described the influence of psychiatric comorbidity on weight gain in AN. Overall, studies were heterogeneous in design, purpose and outcome making comparisons difficult. Findings were divergent but depression had a negative influence on weight gain in four studies.

Background: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a “scar” due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects. Methods: Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters. Discussion: The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and “scar” effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.

Rationale: The psychopathology of anorexia nervosa (AN) includes altered social cognition and information processing of fear and anxiety. Oxytocin, a neuromodulating hormone, may influence these functions and could be valuable for the treatment of AN. Objective: The current study aimed at reviewing the effect of intranasal oxytocin (IN-OT) on attentional bias (AB) and emotion recognition (ER) in AN. Methods: A systematic literature review was done for free-text and the MeSH-terms: anorexia nervosa, feeding and eating disorders, and oxytocin. Six publications, reporting from 4 unique clinical trials, were included in this review. A meta-analysis was conducted to examine the effects of IN-OT on AB towards food images and ER on healthy controls (HC) and patients with AN. Results: Overall, IN-OT did not influence AB towards food images (effect size = 0.20 [− 0.16, 0.57], p = 0.28) and had no effect on ER (effect size = − 0.01 [− 0.27, 0.26], p = 0.97) in patients with AN and healthy control (HC) subjects collectively. Assessing HC and AN separately in subgroup analyses did not show any significant effect on AB and ER in neither of the subgroups. All tests were done between 15 and 55 min post-administration of IN-OT, while peak concentration in the cerebrospinal fluid has been determined to be at 75 min. Conclusion: The current level of evidence is moderate showing no effect of IN-OT on AB or ER in AN. However, brain exposure may not have been sufficient which future studies with IN-OT need to ensure by considering dose and dose-to-task interval.