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Background: The aim of this study was firstly, to improve and validate a cerebrospinal fluid (CSF) prefractionation method followed by two-dimensional electrophoresis (2-DE) and secondly, using this strategy to investigate differences between the CSF proteome of frontotemporal dementia (FTD) patients and controls. From each subject three ml of CSF was prefractionated using liquid phase isoelectric focusing prior to 2-DE. Results: With respect to protein recovery and purification potential, ethanol precipitation of the prefractionated CSF sample was found superior, after testing several sample preparation methods. The reproducibility of prefractionated CSF analyzed on 2-D gels was comparable to direct 2-DE analysis of CSF. The protein spots on the prefractionated 2-D gels had an increased intensity, indicating a higher protein concentration, compared to direct 2-D gels. Prefractionated 2-DE analysis of FTD and control CSF showed that 26 protein spots were changed at least two fold. Using mass spectrometry, 13 of these protein spots were identified, including retinol-binding protein, Zn-α-2-glycoprotein, proapolipoproteinA1, β-2-microglobulin, transthyretin, albumin and alloalbumin. Conclusion: The results suggest that the prefractionated 2-DE method can be useful for enrichment of CSF proteins and may provide a new tool to investigate the pathology of neurodegenerative diseases. This study confirmed reduced levels of retinol-binding protein and revealed some new biomarker candidates for FTD. [ABSTRACT FROM AUTHOR]

Background: We tested if duration and intensity of episodes in treatment-resistant affectively ill patients were related to cerebrospinal fluid (CSF) concentrations of monoamine metabolites. Method: In retrospective life charts were recorded every previous episode of 37 patients with severe treatment-refractory affective disorders. ‘Accumulated burden of mood swings’ (ABMS, sum of each episode length×episode depth) was used to estimate the accumulated illness burden. Homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed in CSF of all patients and compared with 27 healthy controls. Data were analyzed using multiple regression analysis. Results: CSF MHPG contributed strongly significant and positively to the ABMS. Limitations: The retrospective nature of the study. Conclusion: CSF concentrations of MHPG is positively related to ABMS over life. Thus, a specific involvement of norepinephrine in the long-term burden of affective illness is a likely reality. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Despite the fact that eating disorders (EDs) are conditions that are potentially life-threatening, 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-structured 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A method for clinical examination of patients with dementia, stepwise comparative status analysis (STEP), is presented. It combines psychiatric and neurologic status examination methods to identify certain common dementia symptoms by which the patient's regional brain symptom profile can be determined. Fifty status variables (items) are estimated with respect to occurrence and severity. The analysis is performed in three steps. The scores on the 'primary' variables reflect observations of single dementia symptoms. These scores form the basis for the assessment of the 'compound' variables, which in turn form the basis for evaluation of the 'complex' variables, one of which describes the patient's regional (predominant) brain syndrome (subcortical, frontosubcortical, frontal, frontoparietal, parietal, or global). In 96 mildly and moderately demented inpatients, the global (42%) and frontosubcortical (31%) were the most common. Ninety-one percent of the patients with vascular dementia had a predominant frontal and/or subcortical symptomatology. (J Geriatr Psychiatry Neurol 1996; 9:185-199). [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Anorexia Nervosa (AN) is a severe and often enduring disorder characterized by restriction of food intake, low body weight, fear of weight gain, and distorted body image. Investigations on cognition performance in AN patients have yielded conflicting results. Using an established and sensitive computerized cognitive test battery, we aimed to assess core aspects of cognitive function, including attention span, information processing, reasoning, working and episodic memory, in AN patients and controls. Patients were recruited from the Danish Prospective Longitudinal all-comer inclusion study in Eating Disorders (PROLED). Included were 26 individuals with AN and 36 healthy volunteers (HV). All were tested with CogTrack (an online cognitive assessment system) at baseline, and AN patients were tested again at a follow-up time point after weight increase (n = 13). At baseline, AN patients showed faster reaction times in the attention tasks, as well as increased accuracy in grammatical reasoning compared to HV. There were no differences in cognitive function between AN patients and HV in the other cognitive domains measured (sustained attention, working and episodic memory, speed of retrieval, and speed of grammatical reasoning). No differences were visible in the AN sample between baseline and follow-up. Performance did not correlate with any clinical variables in the AN sample. These findings supplement results from other studies suggesting increased concentration and reasoning accuracy in patients suffering from AN, who showed increased performance in cognitive tasks despite their illness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher‐level ecological evidence. Methods: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED‐related inpatient stays in age groups 15–19 and 20–88+, across 1998–2020. Results: Mean length of inpatient stays was inversely correlated to relapse to ED‐related inpatient care within the same year (p < 0.001, R‐squaredadj = 0.5216 and p < 0.00001, R‐squaredadj = 0.5090, in the 15–19 and 20–88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year‐wise relapse rate. Conclusions: Mean length of ED‐related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment. [ABSTRACT FROM AUTHOR]

Glycoproteins in cerebrospinal fluid (CSF) are altered in Alzheimer's Disease (AD) patients compared to control individuals. We have utilized albumin depletion prior to 2D gel electrophoresis to enhance glycoprotein concentration for image analysis as well as structural glycoprotein determination without glycan release using mass spectrometry (MS). The benefits of a direct glycoprotein analysis approach include minimal sample manipulation and retention of structural details. A quantitative comparison of gel-separated glycoprotein isoforms from twelve AD patients and twelve control subjects was performed with glycoprotein-specific and total protein stains. We have also compared glycoforms in pooled CSF obtained from AD patients and control subjects with mass spectrometry. One isoform of α-antitrypsin showed decreased glycosylation in AD patients while another glycosylated isoform of an unassigned protein was up-regulated. Protein expression levels of α-antitrypsin were decreased, while the protein levels of apolipoprotein E and clusterin were increased in AD. No specific glycoform could be specifically assigned to AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Severe malnourishment may reduce cognitive performance in anorexia nervosa (AN). We studied cognitive functioning during intensive nutritional and medical stabilization in patients with severe or extreme AN and investigated associations between weight gain and cognitive improvement., Methods: A few days after admission to a specialized hospital unit, 33 patients with severe or extreme AN, aged 16-42 years, completed assessments of memory, cognitive flexibility, processing speed, and attention. Mean hospitalization was 6 weeks. Patients completed the same assessments at discharge (n = 22) following somatic stabilization and follow-up up to 6 months after discharge (n = 18)., Results: The patients displayed normal cognitive performance at admission compared to normative data. During nutritional stabilization, body weight increased (mean: 11.3%; range 2.6-22.2%) and memory, attention, and processing speed improved (p values: ≤ 0.0002). No relationship between weight gain and cognitive improvement was observed at discharge or follow-up., Conclusions: Cognitive performance at hospital admission was normal in patients with severe or extreme AN and improved during treatment although without association to weight gain. Based on these results, which are in line with previous studies, patients with severe or extreme AN need not be excluded from cognitively demanding tasks, possibly including psychotherapy. As patients may have other symptoms that interfere with psychotherapy, future research could investigate cognitive functioning in everyday life in patients with severe AN., Trial Registration Number: The study is registered at clinicaltrials.gov (NCT02502617)., Level of Evidence: Level III, cohort study., (© 2023. Springer Nature Switzerland AG.)

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 [ 18 F]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 possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

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/m 2 ) 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.

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: 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.

Introduction: Anorexia nervosa (AN) is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN., Objective: To systematically review the literature for evidence of an effect of cannabinoids on (1) weight gain, and (2) other outcomes, in AN., Method: A systematic review was done using three databases Embase, PubMed and Psychinfo. The review was registered in PROSPERO with ID number CRD42019141293 and was done according to PRISMA guidelines., Results: There were 1288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria. Three studies used the same AN population and utilized data from one original study, leaving only two original studies. Both of these were Randomized Controlled Trials that explored the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereof one study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo., Discussion and Conclusion: There are few studies and the level of evidence is low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to adverse events. More research on cannabinoids in anorexia nervosa is warranted, especially its effects on psychopathology., Level of Evidence: Level I, systematic review.

Bulimia Nervosa (BN) is a serious eating disorder, which affects 0.8-2.9% of the young population. The etiology is unknown and biomarkers would support in understanding the pathophysiology of BN, and in identifying BN patients that may benefit from medical treatment. This systematic review aims to answer whether (a) BN deviate from healthy controls in terms of serotonin (5-HT) biomarkers in blood, and whether (b) blood-based 5-HT biomarkers could be used to tailor psychopharmacological treatment in BN. A literature search using PubMed, PsycINFO and Embase was done using the following search terms: "Bulimia Nervosa" AND "serotonin" AND "blood" OR "plasma" OR "serum". 32 studies were included in this systematic review. Several biomarkers and challenge tests were identified and all studies described an association with BN and dysregulation of the 5-HT system compared to healthy controls. Several studies pointed to an association also to borderline symptoms in BN. BN deviate from healthy controls in terms of 5-HT biomarkers in blood supporting an abnormal 5-HT system in BN. 5-HT biomarkers and associated methods could be used to tailor treatment in BN although as yet, most tests described are unpractical for bedside use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This is a case report of a 51-year-old woman with bilateral stress fractures of the pelvic rami and a history of anorexia nervosa (AN). AN is a psychiatric condition of low weight caused by restricted food intake, impaired body image and an exaggerated fear of gaining weight in addition to compensating behaviour such as excessive physical activity. Among patients with AN, reduced bone density is common, and a higher risk of fractures is present. Stress fractures should be suspected in patients, who have AN and experience pain from the musculoskeletal system without a history of trauma.

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.

Body dysmorphic disorder is defined by a preoccupation of one or more non-existent or slight defects or flaws in the physical appearance. The prevalence is 1.7-2.4% in the general population with a higher incidence rate in women. The rate of suicidal ideation is as high as 80%, and up to 25% of the patients attempt to commit suicide. Comorbidities, such as obsessive compulsive disorder, depression, and anxiety, are frequent. These patients may seek cosmetic or dermatologic rather than psychological treatment. In the view of the high prevalence and risk of suicide, recognizing this disorder is important.

Background: Frontotemporal dementia (FTD) is believed to be rare in the elderly, and the influence of different criteria on the prevalence of FTD is unclear., Methods: Population-based samples of 70- to 95-year-olds (n = 2462) in Gothenburg, Sweden, underwent neuropsychiatric examinations. Behavioral variant FTD (bvFTD) was diagnosed according to the International Behavioural Variant FTD Criteria Consortium (FTDC), the Frontotemporal Lobe Degeneration Consensus criteria, and the Lund-Manchester Research Criteria. A subset (n = 1074) underwent computerized tomography (CT) of the brain., Results: The prevalence of bvFTD varied between 0.2% and 0.5% at age 70 to 79 years, between 2.5% and 3.6% at age 80 to 89 years, and between 1.7% and 2.2% at age 90 to 95 years. The agreement between different criteria was low to moderate (κ = 0.20-0.42). Among those with bvFTD according to FTDC, 93.3% had frontal and/or temporal lobar atrophy on CT, compared with 12.6% of those without bvFTD (P < .001)., Conclusions: The prevalence of bvFTD was higher than expected in this population. To a large extent, different criteria captured different individuals., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the "right" control population, and the blood-brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field., (Copyright © 2014 The Alzheimer's Association. All rights reserved.)

Background: Few studies have examined whether cognitive symptom patterns differ by age and length of time before dementia onset. Our objective was to investigate whether different patterns of cognitive symptoms at ages 70, 75, and 79 years predict short-term (< or =5 years) and long-term (>5 years) dementia onset., Methods: A representative sample of 382 nondemented 70-year-olds from Gothenburg, Sweden was examined periodically up to age 90 years. Information on dementia in those lost to follow-up was obtained from medical records. Cognitive assessments at ages 70, 75, and 79 years included psychiatric and psychometric examinations. Four patterns of cognitive performance were examined in relation to dementia onset: (1) unimpaired cognition, (2) isolated low memory, (3) low non-memory, and (4) global low cognitive performance., Results: Short-term onset was predicted by global low performance at ages 70, 75, and 79 years and by low non-memory performance at ages 70 and 75. Isolated low memory was not a short-term predictor at any examination, but it predicted long-term onset at ages 70 and 75 years., Conclusions: A global pattern of low cognitive performance predicts short-term but not long-term onset of dementia, whereas isolated low memory performance predicts dementia only in the long-term. Our findings also suggest that preclinical symptoms of dementia might differ by age.

The heat-shock proteins (HSPs) Hsp27 and alphaB-crystallin are up-regulated in Alzheimer's disease (AD), but the extent of this and the consequences are still largely unknown. The HSPs are involved in protein degradation and protection against protein aggregation, and they interact with several cytoskeletal components such as microtubules (MT) and neurofilaments (NF). AD pathology includes aggregated proteins (tau, NF), decreased protein degradation, and cytoskeletal disruption. It is thus of interest to investigate more closely the possible roles of the HSPs in AD pathology. The expressions of Hsp27 and alphaB-crystallin in AD brain samples were significantly increased (by approximately 20% and approximately 30%, respectively) and correlated significantly with phosphorylated tau and NF proteins. To investigate the consequences of increased HSP levels on tau and NF regulation, N2a cells were transfected with Hsp27 or alphaB-crystallin constructs, and overexpression of the HSPs was confirmed in the cells. Increased tau phosphorylation at the Ser262 site in the N2a cells was regulated by Hsp27 overexpression (possibly through p70S6k), whereas the overexpression of alphaB-crystallin resulted in decreased levels of phosphorylated tau, NF, and GSK-3beta. It was also shown that overexpression of HSPs causes an increase in the percentage of cells present in the G(1) phase. The results presented suggest that a cellular defense against dysregulated proteins, in the form of Hsp27 and alphaB-crystallin, might contribute to the cell cycle reentry seen in AD cells. Furthermore, Hsp27 might also be involved in AD pathology by aggravating MT disruption by tau phosphorylation., (2007 Wiley-Liss, Inc.)

Objective: In clinical guidelines, risk factors for a malignant illness course include 3 or more lifetime episodes of depression. Our aim was to investigate the activation of the hypothalamic-pituitary-adrenal hormonal axis in treatment-refractory affective disorder in pauciepisodic (one or two episodes) versus multiepisodic (three or more episodes) patients., Methods: We evaluated the HPA axis in 37 patients with treatment-refractory affective disorder and in 27 healthy volunteers by measuring adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin-releasing hormone (CRH). In retrospective life charts was recorded every previous illness episode for each patient., Results: Seven of the patients were pauciepisodic and 30 were multiepisodic. The pauciepisodic patients had significantly larger peak and total ACTH responses to CRH compared to the multiepisodic patients as well as to the control group. Multiepisodic patients showed no difference compared to controls in ACTH secretion pre- and post-CRH. Cortisol secretion was the same in all three groups., Conclusions: The pituitary adrenocortical responses were stronger in pauciepisodic patients than in multiepisodic patients and in volunteers. This cross-sectional study suggests that the HPA axis, in refractory multiepisodic affective disorders, might weaken its original activity as the illness recurs with more episodes.

We investigated the clinical and biological effects of cholesterol-lowering treatment with a statin in 19 patients with Alzheimer's disease. They received simvastatin 20 mg/day for 12 weeks in an open trial. Primary efficacy parameters were the changes after 12 weeks in the cerebrospinal fluid (CSF) levels of beta-amyloid(42) (Abeta(42)), alpha-secretase-cleaved amyloid precursor protein (alpha-sAPP), beta-secretase-cleaved APP (beta-sAPP), tau, phospho-tau and the plasma levels of Abeta(42). A secondary efficacy parameter was the change in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog) score. After 12 weeks, CSF alpha-sAPP and CSF beta-sAPP were significantly reduced (p < 0.001), but the CSF levels of tau, phospho-tau, Abeta(42) and the plasma levels of Abeta(42) were unchanged. The ADAS-cog score was slightly increased (p < 0.05). The results suggest that simvastatin acts directly on the processing of APP by inhibiting both the alpha- and the beta-secretase pathways., (Copyright 2003 S. Karger AG, Basel)

Background: Vagus nerve stimulation (VNS) is an established treatment method for therapy-refractory epilepsy and, in Europe, for treatment-resistant depression also. Clinical and experimental investigations have also shown positive effects of VNS on cognition in epilepsy and depression. The purpose of the present pilot study was to investigate the effect of VNS on cognition in patients with Alzheimer's disease., Method: All the included patients (N = 10) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for the diagnosis of Alzheimer's disease. Before the implantation of the vagus stimulator (NeuroCybernetic Prosthesis), the patients underwent neuropsychological tests (e.g., Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-cog] and Mini-Mental State Examination [MMSE]), computerized tomography of the brain, medical/neurologic and psychological examinations (status evaluation), and lumbar puncture with investigation of the cerebrospinal fluid. The presence of depressive symptoms was rated using the Montgomery-Asberg Depression Rating Scale. The VNS was initiated 2 weeks after the implantation, and the patients were followed up with regular investigations and tests over 6 months. Response was defined as improvement or absence of impairment in ADAS-cog and MMSE scores after 3 and 6 months., Results: After 3 months of treatment, 7 of 10 patients were responders according to the ADAS-cog (median improvement of 3.0 points), and 9 of 10 patients were responders according to the MMSE (median improvement of 1.5 points). After 6 months of treatment, 7 patients were responders on the ADAS-cog (median improvement of 2.5 points), and 7 patients were responders on the MMSE (median improvement of 2.5 points). VNS was well tolerated, and its side effects were mild and transient., Conclusion: The results of this open-label pilot study suggest a positive effect of VNS on cognition in patients with Alzheimer's disease. Further studies are warranted.

Creutzfeldt-Jakob's disease and bovine spongiform encephalitis (BSE) are both prion diseases, i.e., diseases caused by an abnormally folded isoform of cellular prion protein. A variant of Creutzfeldt-Jakob's disease can probably be transmitted from cattle with BSE to humans. To prevent spread of BSE, whole stocks of cattle are destroyed when symptoms of the disease appear. However, this is too late to prevent transmission during the about 5 years long incubation time. A method for presymptomatic diagnosis of BSE is clearly desirable. Miele and colleagues at Roslin Institute in Edinburgh present a potential molecular marker for prion diseases in the March issue of Nature Medicine. It is a dramatically decreased expression of a transcript called erythroid differentiation-related factor (EDRF). This change is detectable early in the course of the disease also in tissues outside the central nervous system, for instance blood.

By comparing the CSF proteome between Alzheimer disease (AD) patients and controls it may be possible to identify proteins that play a role in the disease process and thus to study the pathogenesis of AD. We used mini-gel technology in a two-dimensional electrophoresis procedure, sensitive SYPRO Ruby staining and mass spectrometry for clinical screening of disease-influenced CSF proteins in 15 AD patients and 12 controls. The levels of six proteins and their isoforms, including proapolipoprotein, apolipoprotein E, beta-2 microglobulin, retinol-binding protein, transthyretin, and ubiquitin, were significantly altered in CSF of AD patients. The most prominently altered proteins were the apolipoproteins, especially proapolipoprotein.

Both tau and beta-amyloid 42 (Abeta42) have been implicated in Alzheimer's disease (AD) and tau alone in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These proteins can be measured in the cerebrospinal fluid (CSF); differences from normal CSF levels may reflect pathophysiological mechanisms. Using ELISAs, we investigated the levels of total CSF-tau (here referred to as tau), phosphorylated CSF-tau (phosphotau), and Abeta42 in patients with AD (n = 19), FTD (n = 14), ALS (n = 11) and Parkinson's disease (PD; n = 15) and in age-matched controls (n = 17). Both CSF-tau and CSF-phosphotau were increased in AD compared with FTD (p < 0.001), ALS (p < 0.001), PD (p < 0.001) and controls (p < 0.001). CSF-Abeta42 was markedly decreased in AD and ALS (both p < 0.001) and slightly decreased in FTD (p < 0.01) and PD (p < 0.05) compared with controls. Using CSF-phosphotau may improve the differentiation of AD from FTD and ALS in clinical praxis. Furthermore, decreased CSF-Abeta42 levels may be common in neurodegenerative disorders possibly reflecting changes in the metabolism of beta-amyloid or axonal degeneration., (Copyright 2002 S. Karger AG, Basel)