Plasma proteome profiling reveals metabolic and immunologic differences between Anorexia Nervosa subtypes.

AIMS/HYPOTHESIS: Anorexia Nervosa (AN) is a severe psychiatric disorder of an unknown etiology with a crude mortality rate of about 5 % per decade, making it one of the deadliest of all psychiatric illnesses. AN is broadly classified into two main subtypes, restricting and binge/purging disorder. Despite extensive research efforts during several decades, the underlying pathophysiology of AN remains poorly understood. In this study, we aimed to identify novel protein biomarkers for AN by performing a proteomics analysis of fasting plasma samples from 78 females with AN (57 restrictive and 21 binge/purge type) and 70 healthy controls. METHODS: Using state-of-the-art mass spectrometry-based proteomics technology in conjunction with an advanced bioinformatics pipeline, we quantify >500 plasma proteins. RESULTS: Differential expression analysis and correlation of proteomics data with clinical variables led to identification of a panel of novel protein biomarkers with potential pathophysiological significance for AN. Our findings demonstrate evidence of a humoral immune system response, altered lipid metabolism and potential alteration of plasma cells in AN patients. Additionally, we stratified AN patients based on the quantified proteins and suggest a potential autoimmune nature in the restrictive subtype of AN. CONCLUSIONS/INTERPRETATION: In summary, on top of biomarkers of AN subtypes, this study provides a comprehensive map of plasma proteins that constitute a resource for further studies of the pathophysiology of AN.

Prevalence of eating disorder symptomatology among outpatients referred to health promotion from somatic hospital departments.

BACKGROUND AND AIMS: All eating disorders (EDs) lead to a significant decrease of health status, psychosocial functioning and quality of life (QoL). Individuals with untreated binge eating disorder (BED) tend to gain weight over time, which may contribute to serious health issues. In somatic hospital departments, some outpatients have reduced compliance with lifestyle changes. This may, to some extent, be due to patients with an undiagnosed ED receiving the incorrect treatment. In this cross-sectional study, we aimed to investigate the prevalence of EDs among patients referred to lifestyle courses. RESULTS: A total of 136 patients referred from somatic hospital departments to lifestyle changes in a specialized hospital unit were included in the study. The response rate was 69.4%. Self-reported ED or sub-clinical symptoms of ED according to the Eating Disorder Examination Questionnaire (EDE-Q) were found in 17.65%. Of these, 11.03% fulfilled the self-reported criteria for an ED (BED, 7.35%; bulimia nervosa, 3.68%). Patients with an ED or subclinical ED symptoms had elevated grazing behaviour compared to those without ED symptomatology. A statistically significant difference in QoL was also found. DISCUSSION AND CONCLUSIONS: The prevalence of self-reported ED or subclinical ED symptoms in patients referred to a lifestyle course is substantial. This ED group had reduced QoL and larger grazing behaviour compared to patients without ED symptomatology. Thus, the prevalence of undiagnosed EDs among patients within somatic hospital departments may be substantial, underlining the importance of screening and further research within this topic. LEVEL OF EVIDENCE: Level III, well-designed cohort study. SIGNIFICANCE: What is already known on this subject? In a review including populations from Scandinavia, the USA and South America, the estimated BED prevalence in individuals with higher body weight seeking help to lose weight is 13-27% [22]. Dawes et al. (2016) conducted a meta-analysis investigating the prevalence of mental health conditions among bariatric surgery candidates and recipients. They included 25 studies with a total of 13,769 patients and found that the prevalence of BED was 17% (13-21%) [10]. What this study adds? We have identified a group of patients who may be receiving inappropriate treatment with weight loss intervention instead of specialized ED intervention. It appears that this issue is valid in various somatic hospital departments. Thus, this is a field that requires further attention and investigation.

The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice.

Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.

Validation of the Affect Integration Inventory in a sample of patients with personality disorders: A cross-sectional study.

Affect integration is defined as the capacity to comprehend emotional experiences as meaningful and to convert this knowledge into well-adjusted motivation, communication and behavior. Thus, affect integration is considered essential for personal adjustment and well-being, and it has been operationalized through the Affect Integration Inventory. However, the validity of this questionnaire has been examined only in non-clinical respondents. Therefore, the purpose of this study was to investigate the psychometric properties of the questionnaire in a sample of patients with personality disorders (n = 87). The internal structure and consistency were addressed using Cronbach's alpha and confirmatory factor analysis. To determine aspects of convergent and discriminant validity, the correlations between the scores on the questionnaire and the scores on content-related questionnaires and scales were examined. Finally, scores from the clinical respondents and existing data from a previously collected non-clinical sample (n = 157) were compared to evaluate the external validity. The overall results demonstrated satisfactory internal consistency, a consistent factor structure, and systematic patterns of convergent and discriminant validity. Additionally, the findings indicated that the instrument clearly differentiated the clinical sample from the non-clinical sample.

Referral patterns to outpatient child and adolescent mental health services and factors associated with referrals being rejected. A cross-sectional observational study.

BACKGROUND: Outpatient child and adolescent mental health services (CAMHS) are faced with the challenge of balancing increasing demands with limited resources. An additional challenge is high rejection rates of referrals which causes frustration for referring agents and families. In order to effectively plan and allocate available resources within CAMHS there is a need for up-to-date knowledge on referral patterns and factors associated with rejection of referrals. METHODS: In this cross-sectional observational study we did a retrospective review of all referrals (n = 1825) for children (0-18) referred for assessment at the outpatient CAMHS of the North Denmark Region in 2018. RESULTS: The most common referral reasons to CAMHS were attention deficit disorder (ADHD/ADD) (27.9%), autism spectrum disorder (22.4%), affective disorders (14.0%) and anxiety disorders (11.6%). The majority of referrals came from general practitioners, but for neurodevelopmental disorders educational psychologists were the primary referral source. Re-referrals constituted more than a third of all referrals (35.9%). Children in care were overrepresented in this clinical sample and had an increased risk (Adj. OR 2.54) of having their referrals rejected by CAMHS. Referrals from general practitioners were also associated with an increased risk of rejection (Adj. OR 3.29). CONCLUSIONS: A high proportion of children with mental disorders have a repeated need for assessment by CAMHS. There is a need for future research on predictors of re-referral to outpatient services to identify potential targets for reducing re-referral rates as well as research on how to optimize service provision for children with a repeated need for assessment. General practitioners are the main gatekeepers to CAMHS and research on interventions to improve the referral process should be aimed towards general practitioners.

Burnout in Mental Health Care Professionals Working with Inpatients in Open or Closed Wards in Psychiatric Hospitals.

Mental health care professionals are at risk of experiencing burnout. This cross-sectional study aims to investigate burnout in two settings: open and closed psychiatric wards, and two professions: registered nurses and social healthcare assistants in eight psychiatric wards in Denmark. A total of 114 professionals completed the Copenhagen Burnout Inventory and a demographic questionnaire. No statistically differences in burnout in professionals working in closed and open wards were found. However, we found professionals to score highest on personal and work-related burnout and lowest on client-related burnout. This indicates that patients may only play a minor role in burnout in health professionals.

Parent-perceived barriers to accessing services for their child's mental health problems.

BACKGROUND: Many children and adolescents with impairing mental health disorders are not in contact with specialized child and adolescent mental health services (CAMHS). In order to close the service gap, it is important to increase our knowledge of barriers to access. The aim of this study was to investigate parent perceived barriers to accessing services for their child's mental health problems to identify potential areas for improvement of access to CAMHS. METHOD: In this cross-sectional observational study 244 parents of children and adolescents referred to outpatient psychiatric assessment were interviewed using the Children's services interview regarding barriers to accessing child mental health services across healthcare, educational services and social services. Parent reported barriers were analyzed in relation to the child's age, referral reason, symptom duration and impairment of the child. RESULTS: The most commonly reported barriers were lack of information about were to seek help (60.3%), the perception that professionals did not listen (59.8%) and professionals refusing to initiate interventions or provide referral to services (53.7%). Lack of knowledge, stigmatization and unavailability of services were common themes across barriers to help-seeking. Long symptom duration and parent rated impairment was associated with increased risk of reporting several barriers to help-seeking. CONCLUSION: Parents seeking help for their child's mental health encounter numerous barriers that could explain part of the treatment gap and long duration of mental health problems in children prior to referral to CAMHS.

Characteristics of Young Adults with Autism Spectrum Disorder Performing Different Daytime Activities.

Daytime activity, in terms of engagement in an occupation or education, is highly important for individuals with autism spectrum disorder (ASD), regardless of their level of functioning. In this nationwide survey, the parents of young adults diagnosed with ASD in childhood (n = 1266) provided information about the current daytime activity of their child, as well as behavioral characteristics, comorbidity, history of schooling during primary and secondary school, and availability of support. The young adults without a regular daytime activity constituted approximately one-fifth of the sample and had more behavioral difficulties and comorbidities than young adults with a daytime activity. Intellectual disability, part-time job, history of schooling, including type of school, and availability of support were found to be associated with daytime activity.

Quality of life in adolescents and adults with autism spectrum disorder: Results from a nationwide Danish survey using self-reports and parental proxy-reports.

BACKGROUND: Quality of life (QoL) in individuals with autism spectrum disorder (ASD) is essential to investigate with regard to knowledge about factors of importance for QoL and concordance between self-reported and parental proxy-reported QoL. AIMS: This study investigated QoL in adolescents and adults with ASD using both self-reports and parental proxy-reports. METHODS: From a nationwide survey, 1738 individuals diagnosed with ASD in childhood, were included for this study. The individuals themselves and/or their parents completed the INICO-FEAPS scale. Concordance between self-reports and proxy-reports were examined, and factors associated with QoL were explored via linear regression models. RESULTS: Compared to proxy-reported QoL scores, self-reported QoL scores were significantly but only slightly higher and not in every QoL domain. Independent of respondent type it was found that psychiatric comorbidity, sleeping difficulty, intellectual disability, maladaptive behavior, adaptive functioning, autism symptomatology, main daytime activity and residence were associated with QoL. CONCLUSION: Proxy-reported QoL is different from self-reported QoL and should be considered as an alternative source of information. QoL might be enhanced when factors associated with QoL are improved. However, large variations in QoL were found for most factors, suggesting the need to involve the individuals with ASD and/or their families when improving their QoL.

Psychometric properties of the INICO-FEAPS scale in a Danish sample with autism spectrum disorders.

BACKGROUND: There is a need to evaluate subjective perspectives of outcomes, such as quality of life (QoL), in individuals with autism spectrum disorders (ASD), but to date, there is no specific instrument available to assess this population. While the INICO-FEAPS scale is customized for studying QoL in adolescents and adults with intellectual and/or developmental disabilities, this scale has not been previously evaluated in an ASD population. AIMS: To examine the usability of the INICO-FEAPS scale in a Danish population of adolescents and adults with ASD. METHODS: In a nationwide survey, 875 adolescents and adults with ASD and 1573 parents completed the INICO-FEAPS scale. Internal consistency was evaluated through several indices. Confirmatory factor analysis (CFA) was conducted to investigate the fit of the model with eight correlated first-order factors, and convergent validity was explored comparing the results of different QoL measures through correlation analysis. RESULTS: Internal consistency was adequate for the indices applied, and the CFA model tested indicated an acceptable fit to the data. Generally, comparisons of results of different QoL measures resulted in moderate to high correlations. CONCLUSION: Overall, it was concluded that due to the psychometric properties found, the INICO-FEAPS scale is applicable for use in ASD populations.

Bone and vitamin D status in patients with anorexia nervosa.

INTRODUCTION: The aim of the present study was to investigate bone status and biological mechanisms involved in the negative impact of anorexia nervosa (AN) on osteogenesis. METHODS: A total of 30 AN patients from Aalborg University Hospital who underwent bone scans were included in a cross-sectional study. Biochemical data, bone scans (dual-energy X-ray absorptiometry (DXA)) as well as general health and medical information had been collected during the 2009-2011 period and stored via local and national clinical databases in Denmark, and from these databases we identified all patients with an AN diagnosis who underwent bone scans. RESULTS: AN patients had a mean Z-score of -1.5 to -1.6 in lumbar spine and total hip, respectively. The hip Z-score decreased with duration of disease, and a positive correlation was seen between serum 25-hydroxy-vitamin D level and spine Z-score but not hip Z-score. Bone mineral density did not seem to change with time since diagnosis. Additionally, a negative correlation between serum 25-hydroxy-vitamin D levels and serum total alkaline phosphatase levels was found. A serum 25-hydroxy-vitamin D level below 50 nmol/l was associated with increased alkaline phosphatase levels. CONCLUSION: Rather than clinical measures including BMI and biochemical measures disease duration was the main predictor of bone status. This implies that long-term disease should be a main factor in selecting patients for referral to DXA. Moreover, results from this study indicate normal osteoblastic response to malnutrition. FUNDING: not relevant. TRIAL REGISTRATION: The present study was not registered due to its register-based design. However, the study was approved by the Danish Data Protection Agency.

Is the PANSS cognitive scale measuring cognition?

OBJECTIVE: To investigate the association between the Positive and Negative Syndrome Scale (PANSS) cognitive factors and cognition assessed by neuropsychological tests. METHOD: Ninety patients with a psychotic illness, the majority having a schizophrenia diagnosis, were assessed with PANSS ratings and tested by a comprehensive computerized neuropsychological test battery, EuCog. RESULTS: Test performance was in the normal range for some of the cognitive indices, but substantially reduced for others, compared with norms, particularly speed-based indices. PANSS ratings were non-specifically associated with cognitive indices representing performance (speed and accuracy) and problem solving strategies (executive functions). There was no discriminant validity for the cognitive factor. A regression analysis suggested that the PANSS cognitive factors reflected verbal IQ but no other cognitive domain like memory, attention or speed. CONCLUSION: Cognitive test performance is associated with psychopathology as assessed by PANSS items but in a non-specific way. The PANSS cognitive subscale seems to reflect over-learned verbal skills rather than the cognitive domains, which are known to be specifically affected in schizophrenia and relevant for the prognosis. Consequently, PANSS ratings cannot replace the information inherent in neuropsychological test data. The extensive speed problem of patients with schizophrenia should be studied in more detail using test batteries that focus on that problem.