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1.  The outcome of treatment for anorexia nervosa inpatients who required urgent hospitalization 
Background
This study was done to determine which psychosocial factors are related to the urgent hospitalization of anorexia nervosa patients (AN) due to extremely poor physical condition and to evaluate their outcome after inpatient treatment.
Methods
133 hospitalized AN patients were classified into an urgent hospitalization (n = 24) or a planned hospitalization (n = 109) group. Multiple regression analysis was done of clinical features, body mass index (BMI), psychological tests [The Minnesota Multiphasic Personality Inventory (MMPI), alexithymia, relationship with parents, and the Eating Disorder Inventory (EDI)]. The effectiveness of treatment was prospectively determined two years after discharge by the Global Clinical Score (GCS). The hospitalized weight gain and the frequency of outpatient visits were evaluated.
Results
Of the factors assessed, only BMI at admission was related to the necessity of urgent hospitalization (β = − 1.063, P = 0.00). The urgent group had significantly more weight loss after discharge and poorer social adaptation on the GCS, even when the patient had a sufficient increase in body weight during inpatient treatment and an equivalent number of outpatient consultations.
Conclusion
None of the parameters of the psychosocial tests studied were significantly different between the groups. The outcome of the urgent group was poor. Two years after discharge they had difficulty maintaining weight and continued to have poor social adaptation.
doi:10.1186/1751-0759-8-20
PMCID: PMC4163679  PMID: 25225574
Anorexia nervosa; Urgent hospitalization; Outcome; BMI; MMPI; EDI
2.  Anorexia nervosa 
BMJ Clinical Evidence  2011;2011:1011.
Introduction
Anorexia nervosa is characterised by a low body mass index (BMI), fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and up to 0.7% of this age group may be affected. While most people with anorexia nervosa recover completely or partially, about 5% die of the condition, and 20% develop a chronic eating disorder. Young women with anorexia nervosa are at increased risk of bone fractures later in life.
Methods and outcomes
We conducted a systematic review, and aimed to answer the following clinical questions: What are the effects of treatments in anorexia nervosa? What are the effects of interventions to prevent or treat complications of anorexia nervosa? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: atypical antipsychotic drugs, benzodiazepines, cyproheptadine, inpatient/outpatient treatment setting, oestrogen treatment (HRT or oral contraceptives), older-generation antipsychotic drugs, psychotherapy, refeeding, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants.
Key Points
Anorexia nervosa is characterised by a low body mass index (BMI), fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and the condition may affect up to 0.7% of this group.Anorexia nervosa is related to family, sociocultural, genetic, and other biological factors. Psychiatric and personality disorders such as depression, anxiety disorders, obsessive compulsive disorder, and perfectionism are commonly found in people who have anorexia nervosa.Most people with anorexia nervosa recover completely or partially, but about 5% die from the condition and 20% develop a chronic eating disorder.Young women with anorexia nervosa are at increased risk of fractures later in life.Population assessment indicates that risks to fertility may be overstated in those who reach a healthy BMI, but children born to mothers who have recovered from anorexia nervosa seem to have lower birth weights.
There is no strong RCT evidence that any treatments work well for anorexia nervosa. However, there is a gradual accumulation of evidence suggesting that early intervention is effective. Increasing evidence suggests that working with the family may also interrupt the development of a persistent form of the illness, when this work begins early in the disease.
Evidence on the benefits of psychotherapy is unclear.
Refeeding is a necessary and effective component of treatment, but is not sufficient alone. Very limited evidence from a quasi-experimental study suggests that a lenient approach to refeeding is as effective and more acceptable compared with a more strict approach.Refeeding may be as effective in an outpatient setting as during hospital admission.Nasogastric refeeding has been used to speed up weight gain in inpatient observational studies, although it is rarely studied in RCTs. Very limited RCT evidence suggests that adding nasogastric feeding to oral nutrition can increase weight gain and reduce relapse in the short term more than oral nutrition alone, but these gains are not maintained at 1 year post-discharge. Given ethical and medical concerns with tube feeding, this approach is encouraged with caution.Nutritional supplements, including zinc, have only limited evidence for their effectiveness, and additional evaluations of these measures are warranted.
We don't know whether inpatient or outpatient treatment is more effective in people with anorexia nervosa.
Limited evidence from small RCTs has not shown significant weight gain from SSRIs or tricyclic antidepressants, some of which may cause serious adverse effects. Tricyclic antidepressants may cause drowsiness, dry mouth, blurred vision, and a prolonged QT interval in people who have anorexia nervosa. SSRIs have not been shown to be beneficial, but the evidence remains very limited; in the 4 RCTs we found, conclusions were limited because of small trial size and high rates of withdrawal.
Older-generation antipsychotic drugs may prolong the QT interval, increasing the risk of ventricular tachycardia, torsades de pointes, and sudden death. Atypical antipsychotics have been evaluated for their potential role in reducing agitation and anxiety related to refeeding, as well as for potentially increasing appetite. Increasing observational data (case series) have suggested that they may decrease obsessiveness and agitation. However, further evidence from large, well-conducted RCTs is necessary to draw reliable conclusions. Newer atypical antipsychotics, in particular olanzapine, do not seem to be associated with the same cardiac risks as older-generation antipsychotic drugs, but the known association between olanzapine and weight gain may impact compliance in people with anorexia nervosa. However, further research needs to be done.
We found insufficient RCT evidence assessing benzodiazepines or cyproheptadine for treating anorexia nervosa.
Oestrogen treatment has been hypothesised to reduce the negative effects on bone mineral density associated with anorexia nervosa. However, three small RCTs have failed to demonstrate clinically relevant changes in bone mineral density after treatment with oestrogen either HRT or oral contraceptives), and these results are supported by 2-year longitudinal data, which found similar lack of improvement.
PMCID: PMC3275304  PMID: 21481284
3.  Body composition in adolescent idiopathic scoliosis 
European Spine Journal  2012;22(2):324-329.
Study design
A controlled prospective cross-sectional case study.
Objective
To investigate body mass index (BMI) and corporal composition in girls with adolescent idiopathic scoliosis (AIS) and compare them with a normal population matched by sex and age.
Summary and background data
There is controversy as to whether there are real anthropometric alterations in patients with AIS. Relative to the weight or the BMI, some studies find differences and other studies do not detect them. AIS and anorexia nervosa (AN) make their debut during adolescence and both may be associated with an alteration of their subjective physical perception. Some authors propose a link between AIS and AN supported both by an alteration of physical perception and lower BMI. No studies on body composition in AIS have been published.
Methods
Adolescent idiopathic scoliosis patient surgery candidates during 2008 were studied. Body composition was evaluated using the bioelectrical impedance analysis (Bodystat, Isle of Man, UK). A study population of more than 5,000 patients that was published by Kyle et al. (Nutrition 17:534–541, 2001) was chosen as a control (group 1). Another control group (group 2) of healthy volunteers matched by sex and age was selected among a school age and university population in Barcelona, Spain. A variance analysis was used to analyze differences between the mean values of the control group 1, the European control group, and the AIS patient surgery candidates (Epiinfo 6.2001). Comparisons between the AIS patients and control group 2 were performed with the T Student test of unpaired samples using the SPSS 15.0 (Statistical Package Social Science) software.
Results
Twenty-seven women with a mean age of 17.4 years. BMI was 18.9 kg/m2 (SD 1.7; 95 % CI 18.31–19.73). In the variance analysis, a significant difference between AIS and group 1 in BMI was observed (21.0 vs. 18.9, p = 0.000004); fat-free mass (FFM = 42.6 vs. 38.9, p = 0.0000009) and fat mass (FM = 15.6 vs. 13.7, p = 0.03). Significant differences in BMI (22.13 vs. 18.9, p = 0.001; 95 % CI difference 1.85–4.60), fat mass index (FMi = 7.17 vs. 4.97, p = 0.000; 95 % CI difference 1.36–3.05) and fat-free mass index (FFMi = 14.95 vs. 13.09, p = 0.001; 95 % CI difference 0.26–1.86) between AIS and group 2 were also seen.
Conclusion
The conclusion is that there is a real alteration of body composition in AIS. The BMI, FFMi and FMi are lower than in the general population in the series under study.
doi:10.1007/s00586-012-2465-y
PMCID: PMC3555626  PMID: 22886589
Adolescent idiopathic scoliosis; Body mass index; Body composition
4.  Anorexia nervosa 
BMJ Clinical Evidence  2009;2009:1011.
Introduction
Anorexia nervosa is characterised by a low body mass index (BMI), fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and up to 0.7% of this age group may be affected. While most people with anorexia nervosa recover completely or partially, about 5% die of the condition, and 20% develop a chronic eating disorder. Young women with anorexia nervosa are at increased risk of bone fractures later in life.
Methods and outcomes
We conducted a systematic review which aimed to answer the following clinical questions: What are the effects of treatments for anorexia nervosa? What are the effects of interventions to prevent or treat complications of anorexia nervosa? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anxiolytic drugs, cyproheptadine, inpatient/outpatient treatment setting, oestrogen treatment, psychotherapy, refeeding, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants.
Key Points
Anorexia nervosa is characterised by a low BMI, fear of gaining weight, denial of current low weight and its impact on health, and amenorrhoea. Estimated prevalence is highest in teenage girls, and may affect up to 0.7% of this group.Anorexia nervosa is related to family, sociocultural, genetic, and other biological factors. Psychiatric and personality disorders such as depression, anxiety disorders, obsessive compulsive disorder, and perfectionism, are commonly found in people who have anorexia nervosa.Most people with anorexia nervosa recover completely or partially, but about 5% die from the condition and 20% develop a chronic eating disorder.Young women with anorexia nervosa are at increased risk of fractures later in life.
There is no strong research evidence that any treatments work well for anorexia nervosa. However, there is a gradual accumulation of evidence which suggests that early intervention is effective. Working with the family may also interrupt the development of a persistent form of the illness.
Evidence on the benefits of psychotherapy is unclear.
Refeeding is a necessary and effective component of treatment, but is not sufficient alone. Very limited evidence from a quasi-experimental study suggests that a lenient approach to refeeding is as effective and more acceptable compared with a more strict approach.Refeeding may be as effective in an outpatient setting as during hospital admission.Nasogastric feeding is rarely required and can lead to problems due to hypophosphataemia.Nutritional supplements, including zinc, have only limited evidence for their effectiveness, and additional evaluation of these measures are warranted.
Limited evidence from small RCTs has not shown significant weight gain from SSRIs or tricyclic antidepressants, some of which may cause serious adverse effects. Tricyclic antidepressants may cause drowsiness, dry mouth, blurred vision, and a prolonged QT interval in people who have anorexia nervosa. SSRIs have not been shown to be beneficial, but the evidence remains very limited; in the four RCTs we found, conclusions were limited due to small trial size and high withdrawal rates.
Anxiolytic drugs (mainly older generation antipsychotic drugs) may prolong the QT interval, increasing the risk of ventricular tachycardia, torsades de pointes, and sudden death. Atypical antipsychotics have been evaluated for their potential role in reducing agitation and anxiety related to refeeding, as well as for potentially increasing appetite. Weak observational evidence has suggested that they may decrease obsessiveness and agitation. However, we found no RCTs of sufficient quality on the effects of atypical antipsychotics, and further evidence from large, well-conducted RCTs is necessary to draw reliable conclusions. Some atypical antipsychotics do not appear to be associated with the same cardiac risks as older-generation antipsychotic drugs. However, further research needs to be done.
We found insufficient evidence assessing cyproheptadine for treating anorexia nervosa.
Oestrogen treatment has been hypothesized to reduce the negative effects on bone mineral density associated with anorexia nervosa. However, three small RCTs have failed to demonstrate significant changes in bone mineral density after treatment with oestrogen.
PMCID: PMC2907776  PMID: 19445758
5.  Complement C3 serum levels in anorexia nervosa: a potential biomarker for the severity of disease? 
Background
Anorexia nervosa carries the highest mortality rate of any psychiatric disorder. Even the most critically ill anorexic patients may present with normal 'standard' laboratory values, underscoring the need for a new sensitive biomarker. The complement cascade, a major component of innate immunity, represents a driving force in the pathophysiology of multiple inflammatory disorders. The role of complement in anorexia nervosa remains poorly understood. The present study was designed to evaluate the role of complement C3 levels, the extent of complement activation and of complement hemolytic activity in serum, as potential new biomarkers for the severity of anorexia nervosa.
Patients and methods
This was a prospective cohort study on 14 patients with severe anorexia nervosa, as defined by a body mass index (BMI) <14 kg/m2. Serum samples were obtained in a biweekly manner until hospital discharge. A total of 17 healthy subjects with normal BMI values served as controls. The serum levels of complement C3, C3a, C5a, sC5b-9, and of the 50% hemolytic complement activity (CH50) were quantified and correlated with the BMIs of patients and control subjects.
Results
Serum C3 levels were significantly lower in patients with anorexia nervosa than in controls (median 3.7 (interquartile range (IQR) 2.5-4.9) vs 11.4 (IQR 8.9-13.7, P <0.001). In contrast, complement activation fragments and CH50 levels were not significantly different between the two groups. There was a strong correlation between index C3 levels and BMI (Spearman correlation coefficient = 0.71, P <0.001).
Conclusions
Complement C3 serum levels may represent a sensitive new biomarker for monitoring the severity of disease in anorexia nervosa. The finding from this preliminary pilot study will require further investigation in future prospective large-scale multicenter trials.
doi:10.1186/1744-859X-10-16
PMCID: PMC3110119  PMID: 21542928
6.  The MOSAIC study - comparison of the Maudsley Model of Treatment for Adults with Anorexia Nervosa (MANTRA) with Specialist Supportive Clinical Management (SSCM) in outpatients with anorexia nervosa or eating disorder not otherwise specified, anorexia nervosa type: study protocol for a randomized controlled trial 
Trials  2013;14:160.
Background
Anorexia nervosa (AN) is a biologically based serious mental disorder with high levels of mortality and disability, physical and psychological morbidity and impaired quality of life. AN is one of the leading causes of disease burden in terms of years of life lost through death or disability in young women. Psychotherapeutic interventions are the treatment of choice for AN, but the results of psychotherapy depend critically on the stage of the illness. The treatment response in adults with a chronic form of the illness is poor and drop-out from treatment is high. Despite the seriousness of the disorder the evidence-base for psychological treatment of adults with AN is extremely limited and there is no leading treatment. There is therefore an urgent need to develop more effective treatments for adults with AN. The aim of the Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related Conditions (MOSAIC) is to evaluate the efficacy and cost effectiveness of two outpatient treatments for adults with AN, Specialist Supportive Clinical Management (SSCM) and the Maudsley Model of Treatment for Adults with Anorexia Nervosa (MANTRA).
Methods/Design
138 patients meeting the inclusion criteria are randomly assigned to one of the two treatment groups (MANTRA or SSCM). All participants receive 20 once-weekly individual therapy sessions (with 10 extra weekly sessions for those who are severely ill) and four follow-up sessions with monthly spacing thereafter. There is also optional access to a dietician and extra sessions involving a family member or a close other. Body weight, eating disorder- related symptoms, neurocognitive and psychosocial measures, and service use data are measured during the course of treatment and across a one year follow up period. The primary outcome measure is body mass index (BMI) taken at twelve months after randomization.
Discussion
This multi-center study provides a large sample size, broad inclusion criteria and a follow-up period. However, the study has to contend with difficulties directly related to running a large multi-center randomized controlled trial and the psychopathology of AN. These issues are discussed.
Trial Registration
Current Controlled Trials ISRCTN67720902 - A Maudsley outpatient study of treatments for anorexia nervosa and related conditions.
doi:10.1186/1745-6215-14-160
PMCID: PMC3679869  PMID: 23721562
Anorexia nervosa; Eating disorder not otherwise specified; Outpatient treatment; Randomized controlled trial; Cost effectiveness
7.  The ANTOP study: focal psychodynamic psychotherapy, cognitive-behavioural therapy, and treatment-as-usual in outpatients with anorexia nervosa - a randomized controlled trial 
Trials  2009;10:23.
Background
Anorexia nervosa is a serious eating disorder leading to high morbidity and mortality as a result of both malnutrition and suicide. The seriousness of the disorder requires extensive knowledge of effective treatment options. However, evidence for treatment efficacy in this area is remarkably weak. A recent Cochrane review states that there is an urgent need for large, well-designed treatment studies for patients with anorexia nervosa. The aim of this particular multi-centre study is to evaluate the efficacy of two standardized outpatient treatments for patients with anorexia nervosa: focal psychodynamic (FPT) and cognitive behavioural therapy (CBT). Each therapeutic approach is compared to a "treatment-as-usual" control group.
Methods/Design
237 patients meeting eligibility criteria are randomly and evenly assigned to the three groups – two intervention groups (CBT and FPT) and one control group. The treatment period for each intervention group is 10 months, consisting of 40 sessions respectively. Body weight, eating disorder related symptoms, and variables of therapeutic alliance are measured during the course of treatment. Psychotherapy sessions are audiotaped for adherence monitoring. The treatment in the control group, both the dosage and type of therapy, is not regulated in the study protocol, but rather reflects the current practice of established outpatient care. The primary outcome measure is the body mass index (BMI) at the end of the treatment (10 months after randomization).
Discussion
The study design surmounts the disadvantages of previous studies in that it provides a randomized controlled design, a large sample size, adequate inclusion criteria, an adequate treatment protocol, and a clear separation of the treatment conditions in order to avoid contamination. Nevertheless, the study has to deal with difficulties specific to the psychopathology of anorexia nervosa. The treatment protocol allows for dealing with the typically occurring medical complications without dropping patients from the protocol. However, because patients are difficult to recruit and often ambivalent about treatment, a drop-out rate of 30% is assumed for sample size calculation. Due to the ethical problem of denying active treatment to patients with anorexia nervosa, the control group is defined as "treatment-as-usual".
Trial registration
Current Controlled Trials ISRCTN72809357
doi:10.1186/1745-6215-10-23
PMCID: PMC2683809  PMID: 19389245
8.  Dysfunctional metacognition and drive for thinness in typical and atypical anorexia nervosa 
Background
Anorexia nervosa is complex and difficult to treat. In cognitive therapies the focus has been on cognitive content rather than process. Process-oriented therapies may modify the higher level cognitive processes of metacognition, reported as dysfunctional in adult anorexia nervosa. Their association with clinical features of anorexia nervosa, however, is unclear. With reclassification of anorexia nervosa by DSM-5 into typical and atypical groups, comparability of metacognition and drive for thinness across groups and relationships within groups is also unclear. Main objectives were to determine whether metacognitive factors differ across typical and atypical anorexia nervosa and a non-clinical community sample, and to explore a process model by determining whether drive for thinness is concurrently predicted by metacognitive factors.
Methods
Women receiving treatment for anorexia nervosa (n = 119) and non-clinical community participants (n = 100), aged between 18 and 46 years, completed the Eating Disorders Inventory (3rd Edition) and Metacognitions Questionnaire (Brief Version). Body Mass Index (BMI) of 18.5 kg/m2 differentiated between typical (n = 75) and atypical (n = 44) anorexia nervosa. Multivariate analyses of variance and regression analyses were conducted.
Results
Metacognitive profiles were similar in both typical and atypical anorexia nervosa and confirmed as more dysfunctional than in the non-clinical group. Drive for thinness was concurrently predicted in the typical patients by the metacognitive factors, positive beliefs about worry, and need to control thoughts; in the atypical patients by negative beliefs about worry and, inversely, by cognitive self-consciousness, and in the non-clinical group by cognitive self-consciousness.
Conclusions
Despite having a healthier weight, the atypical group was as severely affected by dysfunctional metacognitions and drive for thinness as the typical group. Because metacognition concurrently predicted drive for thinness in both groups, a role for process-oriented therapy in adults is suggested. Implications are discussed.
doi:10.1186/s40337-015-0060-4
PMCID: PMC4491244  PMID: 26146555
Anorexia nervosa; Atypical anorexia nervosa; Metacognition; Drive for thinness
9.  Correlation between Body Composition and Walking Capacity in Severe Obesity 
PLoS ONE  2015;10(6):e0130268.
Background
Obesity is associated with mobility reduction due to mechanical factors and excessive body fat. The six-minute walk test (6MWT) has been used to assess functional capacity in severe obesity.
Objective
To determine the association of BMI, total and segmental body composition with distance walked (6MWD) during the six-minute walk test (6MWT) according to gender and obesity grade.
Setting
University of São Paulo Medical School, Brazil; Public Practice.
Methods
Functional capacity was assessed by 6MWD and body composition (%) by bioelectrical impedance analysis in 90 patients.
Results
The mean 6MWD was 514.9 ± 50.3 m for both genders. The male group (M: 545.2 ± 46.9 m) showed a 6MWD higher (p = 0.002) than the female group (F: 505.6 ± 47.9 m). The morbid obese group (MO: 524.7 ± 44.0 m) also showed a 6MWD higher (p = 0.014) than the super obese group (SO: 494.2 ± 57.0 m). There was a positive relationship between 6MWD and fat free mass (FFM), FFM of upper limps (FFM_UL), trunk (FFM_TR) and lower limbs (FFM_LL). Female group presented a positive relationship between 6MWD and FFM, FFM_UL and FFM_LL and male group presented a positive relationship between 6MWD and FFM_TR. In morbid obese group there was a positive relationship between 6MWD with FFM, FFM_UL, FFM_TR and FFM_LL. The super obese group presented a positive relationship between 6MWD with FFM, FFM_TR and FFM_LL.
Conclusions
Total and segmental FFM is associated with a better walking capacity than BMI.
doi:10.1371/journal.pone.0130268
PMCID: PMC4476574  PMID: 26098769
10.  A case series investigation of association between co-morbid psychiatric disorder and the improvement in body mass index among patients with anorexia nervosa and eating disorder not otherwise specified of the anorexia nervosa type 
Background
Anorexia nervosa and eating disorder not otherwise specified* (not fulfilling Anorexia Nervosa DSM IV criteria) are increasing in Singapore. Patients with eating disorders may also present with other psychiatric disorders such as depression and anxiety. The paper aims to investigate the association of co-morbid psychiatric disorders with the improvement of body mass index (BMI) in these patients.
Methods
A retrospective cohort analysis of 182 patients with anorexia and eating disorder not otherwise specified at a tertiary hospital was done. The clinical course of co-morbid psychiatric disorders was correlated with the improvement of body mass index.
Results
109 patients were included in the analysis and the mean BMI on resolution of co-morbid psychiatric disorders was BMI 16.9. There is a significant association between the BMI groups and the resolution of co-morbid psychiatric disorders, χ2 = 10.2, p = .03. Patients in BMI group 5 (BMI 16.6 - 18.5) were noted to be significantly less likely to resolve their psychiatric co-morbidity compared to the other 4 groups. (OR = 0.323).
Conclusion
Patients with anorexia nervosa and eating disorders not otherwise specified were at increased risk of having co-morbid psychiatric disorders and the clinical course of co-morbid psychiatric disorders appeared to correlate with improved BMI. Specifically patients with BMI < 16.5 with co-morbid psychiatric disorders were more likely to recover from their co-morbid psychiatric disorder with nutritional rehabilitation than patients with a higher BMI.
doi:10.1186/s40337-015-0049-z
PMCID: PMC4379948  PMID: 25830025
Personality; Anorexia nervosa; Depression; Generalized anxiety disorder; Body mass index
11.  Serum brain-derived neurotrophic factor and peripheral indicators of the serotonin system in underweight and weight-recovered adolescent girls and women with anorexia nervosa 
Background
Brain-derived neurotrophic factor (BDNF) mutant mice show hyperphagia and hyperleptinemia. Animal and cell-culture experiments suggest multiple interrelations between BDNF and the serotonin (5-HT) system. We studied serum BDNF in patients with anorexia nervosa and its associations with peripheral indicators of the 5-HT system. To control for secondary effects of acute malnutrition, we assessed acutely underweight patients with anorexia nervosa (acAN) in comparison to long-term weight-recovered patients with the disorder (recAN) and healthy controls.
Methods
We determined serum BDNF, platelet 5-HT content and platelet 5-HT uptake in 33 patients in the acAN group, 20 patients in the recAN group and 33 controls. Plasma leptin served as an indicator of malnutrition.
Results
Patients in the acAN group were aged 14–29 years and had a mean body mass index (BMI) of 14.9 (standard deviation [SD] 1.4) kg/m2. Those in the recAN group were aged 15–29 years and had a mean BMI of 20.5 (SD 1.3) kg/m2 and the controls were aged 15–26 years and had a BMI of 21.4 (SD 2.1) kg/m2. The mean serum BDNF levels were significantly increased in the recAN group compared with the acAN group (8820, SD 3074 v. 6161, SD 2885 pg/mL, U = 154.5, p = 0.001). There were no significant associations between BDNF and either platelet 5-HT content or platelet 5-HT uptake. Among patients with anorexia nervosa, we found significant positive linear relations between BDNF and BMI (r = 0.312, p = 0.023) and between BDNF and leptin (r = 0.365, p = 0.016).
Limitations
We measured the signal proteins under study in peripheral blood.
Conclusion
Serum BDNF levels in patients with anorexia nervosa depend on the state of illness and the degree of hypoleptinemia. Upregulation of BDNF in weight-recovered patients with anorexia nervosa could be part of a regenerative process after biochemical and molecular neuronal injury due to prolonged malnutrition. Associations between the BDNF and the 5-HT system in humans remain to be established.
PMCID: PMC2702450  PMID: 19568484
12.  Disruption of brain white matter microstructure in women with anorexia nervosa 
Background
The etiology of anorexia nervosa is still unknown. Multiple and distributed brain regions have been implicated in its pathophysiology, implying a dysfunction of connected neural circuits. Despite these findings, the role of white matter in anorexia nervosa has been rarely assessed. In this study, we used diffusion tensor imaging (DTI) to characterize alterations of white matter microstructure in a clinically homogeneous sample of patients with anorexia nervosa.
Methods
Women with anorexia nervosa (restricting subtype) and healthy controls underwent brain DTI. We used tract-based spatial statistics to compare fractional anisotropy (FA) and mean diffusivity (MD) maps between the groups. Furthermore, axial (AD) and radial diffusivity (RD) measures were extracted from regions showing group differences in either FA or MD.
Results
We enrolled 19 women with anorexia nervosa and 19 healthy controls in our study. Patients with anorexia nervosa showed significant FA decreases in the parietal part of the left superior longitudinal fasciculus (SLF; pFWE < 0.05), with increased MD and RD but no differences in AD. Patients with anorexia nervosa also showed significantly increased MD in the fornix (pFWE < 0.05), accompanied by decreased FA and increased RD and AD.
Limitations
Limitations include our modest sample size and cross-sectional design.
Conclusion
Our findings support the presence of white matter pathology in patients with anorexia nervosa. Alterations in the SLF and fornix might be relevant to key symptoms of anorexia nervosa, such as body image distortion or impairments in body–energy–balance and reward processes. The differences found in both areas replicate those found in previous DTI studies and support a role for white matter pathology of specific neural circuits in individuals with anorexia nervosa.
doi:10.1503/jpn.130135
PMCID: PMC4214871  PMID: 24913136
13.  Effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified: study protocol of a randomized controlled trial 
BMC Psychiatry  2013;13:310.
Background
Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological, physical and social morbidity. Yet, the threshold for seeking professional care is still high. In the Netherlands, only 7.5% of patients with bulimia nervosa and 33% of patients with anorexia nervosa are treated within the mental health care system. Easily accessible and low-threshold interventions, therefore, are needed urgently. The internet has great potential to offer such interventions. The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified.
Methods/design
This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group. In the web-based treatment program, participants will communicate personally and asynchronously with their therapists exclusively via the internet. The first part of the program will focus on analyzing eating attitudes and behaviors. In the second part of the program participants will learn how to change their attitudes and behaviors. Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks, after which they can start the program. The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire. Secondary outcomes include improvements in body image, physical and mental health, body weight, self-esteem, quality of life, and social contacts. In addition, the participants’ motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured. The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs.
Discussion
This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa, binge eating disorder and eating disorders not otherwise specified.
Trial registration
The protocol for this study is registered with the Netherlands Trial Registry NTR2415.
doi:10.1186/1471-244X-13-310
PMCID: PMC3840645  PMID: 24238630
Eating disorders; Bulimia nervosa; Binge eating disorder; Eating disorders not otherwise specified; Randomized controlled trial; Web-based treatment program; e-health; Intensive therapeutic support; Asynchronous support
14.  Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation 
Background and aims
There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones.
Methods
3-9 years (mean 5.2 ± 1.7) after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC) and bone mineral density (BMD) as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I).
Results
The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m2, resumption of menses). Clinical improvement was correlated with BMC and BMD accrual (χ2 = 5.62/χ2 = 6.65, p = 0.06 / p = 0.036). The duration of amenorrhea had a negative correlation with BMD (r = -.362; p < 0.01), but not with BMC. Regular physical activity tended to show a positive effect on bone recovery, but the effect of hormone replacement therapy was not significant. Using age-related standards, the post-discharge sample for the substudy presented IGF-I levels below the 5th percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters.
Conclusions
Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN.
doi:10.1186/1753-2000-4-20
PMCID: PMC2914652  PMID: 20615217
15.  Plasma bile acids show a positive correlation with body mass index and are negatively associated with cognitive restraint of eating in obese patients 
Bile acids may be involved in the regulation of food intake and energy metabolism. The aim of the study was to investigate the association of plasma bile acids with body mass index (BMI) and the possible involvement of circulating bile acids in the modulation of physical activity and eating behavior. Blood was obtained in a group of hospitalized patients with normal weight (BMI 18.5–25 kg/m2), underweight (anorexia nervosa, BMI < 17.5 kg/m2) and overweight (obesity with BMI 30–40, 40–50 and >50 kg/m2, n = 14–15/group) and plasma bile acid concentrations assessed. Physical activity and plasma bile acids were measured in a group of patients with anorexia nervosa (BMI 14.6 ± 0.3 kg/m2, n = 43). Lastly, in a population of obese patients (BMI 48.5 ± 0.9 kg/m2, n = 85), psychometric parameters related to disordered eating and plasma bile acids were assessed. Plasma bile acids showed a positive correlation with BMI (r = 0.26, p = 0.03) in the population of patients with broad range of BMI (9–85 kg/m2, n = 74). No associations were observed between plasma bile acids and different parameters of physical activity in anorexic patients (p > 0.05). Plasma bile acids were negatively correlated with cognitive restraint of eating (r = −0.30, p = 0.008), while no associations were observed with other psychometric eating behavior-related parameters (p > 0.05) in obese patients. In conclusion, these data may point toward a role of bile acids in the regulation of body weight. Since plasma bile acids are negatively correlated with the cognitive restraint of eating in obese patients, this may represent a compensatory adaptation to prevent further overeating.
doi:10.3389/fnins.2015.00199
PMCID: PMC4452824  PMID: 26089773
anorexia; body mass index; eating behavior; obesity; physical activity; psychometric; stress
16.  Resting tachycardia, a warning sign in anorexia nervosa: case report 
Background
Among psychiatric disorders, anorexia nervosa has the highest mortality rate. During an exacerbation of this illness, patients frequently present with nonspecific symptoms. Upon hospitalization, anorexia nervosa patients are often markedly bradycardic, which may be an adaptive response to progressive weight loss and negative energy balance. When anorexia nervosa patients manifest tachycardia, even heart rates in the 80–90 bpm range, a supervening acute illness should be suspected.
Case presentation
A 52-year old woman with longstanding anorexia nervosa was hospitalized due to progressive leg pain, weakness, and fatigue accompanied by marked weight loss. On physical examination she was cachectic but in no apparent distress. She had fine lanugo-type hair over her face and arms with an erythematous rash noted on her palms and left lower extremity. Her blood pressure was 96/50 mm Hg and resting heart rate was 106 bpm though she appeared euvolemic. Laboratory tests revealed anemia, mild leukocytosis, and hypoalbuminemia. She was initially treated with enteral feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis without fever and worsening left leg pain prompted the diagnosis of an indolent left lower extremity cellulitis. With antibiotic therapy her heart rate decreased to 45 bpm despite minimal restoration of body weight.
Conclusions
Bradycardia is a characteristic feature of anorexia nervosa particularly with significant weight loss. When anorexia nervosa patients present with nonspecific symptoms, resting tachycardia should prompt a search for potentially life-threatening conditions.
doi:10.1186/1471-2261-4-10
PMCID: PMC503388  PMID: 15257758
anorexia nervosa; bradycardia; tachycardia; malnutrition
17.  Energy expenditure and body composition in children with Crohn's disease: effect of enteral nutrition and treatment with prednisolone 
Gut  1997;41(2):203-208.
Background—Malnutrition and growth retardation are common complications of Crohn's disease in children. The contribution of resting energy expenditure (REE) to malnutrition is unclear. 
Aims—To characterise the REE and body composition in children with Crohn's disease and compare them with normal controls and patients with anorexia nervosa; to compare the effects of prednisolone and enteral nutrition on energy expenditure and body composition. 
Subjects—Twenty four children with Crohn's disease, 19 malnourished females with anorexia nervosa, and 22 healthy control subjects were studied. 
Methods—In children with Crohn's disease measurements were done when the disease was acute and repeated at one and three months after treatment with either prednisolone or enteral nutrition. Resting energy expenditure was measured by indirect calorimetry and body composition by anthropometry, bioelectrical impedance analysis, total body potassium, H218O, and bromide space studies. 
Results—Body weight and ideal body weight were significantly lower in patients with Crohn's disease than in healthy controls. Lean tissue was depleted and there was an increase in extracellular water. Per unit of lean body mass, there was no difference between REE in patients with Crohn's disease and controls, whereas patients with anorexia nervosa had significantly reduced REE. With enteral nutrition all body compartments and REE increased significantly (p<0.001). In a subgroup of age-matched men there was a significant increase in height after three months of enteral nutrition compared with prednisolone (p<0.01). Those treated with steroids did not show a significant change in height but did show an increase in all body compartments. However, intracellular water as well as lean body mass accretion were significantly higher in the enteral nutrition group than in the prednisolone group. 
Conclusions—Despite being malnourished, children with Crohn's disease fail to adapt their REE per unit of lean body mass. This might be a factor contributing to their malnutrition. Lean tissue accretion is higher in patients treated with enteral nutrition than in those treated with prednisolone. 


Keywords: Crohn's disease; resting energy expenditure; body composition; anorexia nervosa; prednisolone; enteral nutrition
PMCID: PMC1891449  PMID: 9301499
18.  Aged-Related Changes in Body Composition and Association between Body Composition with Bone Mass Density by Body Mass Index in Chinese Han Men over 50-year-old 
PLoS ONE  2015;10(6):e0130400.
Objectives
Aging, body composition, and body mass index (BMI) are important factors in bone mineral density (BMD). Although several studies have investigated the various parameters and factors that differentially influence BMD, the results have been inconsistent. Thus, the primary goal of the present study was to further characterize the relationships of aging, body composition parameters, and BMI with BMD in Chinese Han males older than 50 years.
Methods
The present study was a retrospective analysis of the body composition, BMI, and BMD of 358 Chinese male outpatients between 50 and 89 years of age that were recruited from our hospital between 2009 and 2011. Qualified subjects were stratified according to age and BMI as follows: 50–59 (n = 35), 60–69 (n = 123), 70–79 (n = 93), and 80–89 (n = 107) years of age and low weight (BMI: < 20 kg/m2; n = 21), medium weight (20 ≤ BMI < 24 kg/m2; n = 118), overweight (24 ≤ BMI < 28 kg/m2; n = 178), and obese (BMI ≥ 28 kg/m2; n = 41). Dual-energy X-ray absorptiometry (DEXA) was used to assess bone mineral content (BMC), lean mass (LM), fat mass (FM), fat-free mass (FFM), lumbar spine (L1-L4) BMD, femoral neck BMD, and total hip BMD. Additionally, the FM index (FMI; FM/height2), LM index (LMI; LM/height2), FFM index (FFMI; [BMC+LM]/height2), percentage of BMC (%BMC; BMC/[BMC+FM+LM] × 100%), percentage of FM (%FM; FM/[BMC+FM+LM] × 100%), and percentage of LM (%LM; LM/(BMC+FM+LM) × 100%) were calculated. Osteopenia or osteoporosis was identified using the criteria and T-score of the World Health Organization.
Results
Although there were no significant differences in BMI among the age groups, there was a significant decline in height and weight according to age (p < 0.0001 and p = 0.0002, respectively). The LMI and FFMI also declined with age (both p < 0.0001) whereas the FMI exhibited a significant increase that peaked in the 80-89-years group (p = 0.0145). Although the absolute values of BMC and LM declined with age (p = 0.0031 and p < 0.0001, respectively), there was no significant difference in FM. In terms of body composition, there were no significant differences in %BMC but there was an increase in %FM (p < 0.0001) and a decrease in %LM (p < 0.0001) with age. The femoral neck and total hip BMD significantly declined with age (p < 0.0001 and p = 0.0027, respectively) but there were no differences in L1-L4. BMD increased at all sites (all p < 0.01) as BMI increased but there were declines in the detection rates of osteoporosis and osteopenia (both p < 0.001). A logistic regression revealed that when the medium weight group was given a BMI value of 1, a decline in BMI was an independent risk factor of osteoporosis or osteopenia, while an increase in BMI was a protective factor for BMD. At the same time, BMD in L1-L4 exhibited a significant positive association with FMI (p = 0.0003) and the femoral neck and total hip BMDs had significant positive associations with FFMI and LMI, respectively (both p < 0.0001).
Conclusions
These data indicate that LMI and FFMI exhibited significant negative associations with aging in Chinese Han males older than 50 years, whereas FMI had a positive association. BMD in the femoral neck and total hip declined with age but an increased BMI was protective for BMD. LMI and FFMI were protective for BMD in the femoral neck and total hip.
doi:10.1371/journal.pone.0130400
PMCID: PMC4475062  PMID: 26090818
19.  Cardiac abnormalities in young women with anorexia nervosa. 
British Heart Journal  1994;71(3):287-292.
OBJECTIVE--To identify the characteristics of cardiac involvement in the self-induced starvation phase of anorexia nervosa. METHODS--Doppler echocardiographic indices of left ventricular geometry, function, and filling were examined in 21 white women (mean (SD) 22 (5) years) with anorexia nervosa according to the DSMIII (Diagnostic and Statistical Manual of Mental Disorders) criteria, 19 women (23 (2) years) of normal weight, and 22 constitutionally thin women (21 (4) years) with body mass index < 20. RESULTS--13 patients (62%) had abnormalities of mitral valve motion compared with one normal weight woman and two thin women (p < 0.001) v both control groups). Left ventricular chamber dimension and mass were significantly less in women with anorexia nervosa than in either the women of normal weight or the thin women, even after standardisation for body size or after controlling for blood pressure. There were no substantial changes in left ventricular shape. Midwall shortening as a percentage of the values predicted from end systolic stress was significantly lower in the starving patients than in women of normal weight: when endocardial shortening was used as the index this difference was overestimated. The cardiac index was also significantly reduced in anorexia nervosa because of a low stroke index and heart rate. The total peripheral resistance was significantly higher in starving patients than in both control groups. The left atrial dimension was significantly smaller in anorexia than in the women of normal weight and the thin women, independently of body size. The transmitral flow velocity E/A ratio was significantly higher in anorexia than in both the control groups because of the reduction of peak velocity A. When data from all three groups were pooled the flow velocity E/A ratio was inversely related to left atrial dimension (r = -0.43, p < 0.0001) and cardiac output (r = -0.64, p < 0.0001) independently of body size. CONCLUSIONS--Anorexia nervosa caused demonstrable abnormalities of mitral valve motion and reduced left ventricular mass and filling associated with systolic dysfunction.
PMCID: PMC483668  PMID: 8142200
20.  Use of Fat Mass and Fat Free Mass Standard Deviation Scores Obtained Using Simple Measurement Methods in Healthy Children and Patients: Comparison with the Reference 4-Component Model 
PLoS ONE  2013;8(5):e62139.
Background
Clinical application of body composition (BC) measurements for individual children has been limited by lack of appropriate reference data.
Objectives
(1) To compare fat mass (FM) and fat free mass (FFM) standard deviation scores (SDS) generated using new body composition reference data and obtained using simple measurement methods in healthy children and patients with those obtained using the reference 4-component (4-C) model; (2) To determine the extent to which scores from simple methods agree with those from the 4-C model in identification of abnormal body composition.
Design
FM SDS were calculated for 4-C model, dual-energy X-ray absorptiometry (DXA; GE Lunar Prodigy), BMI and skinfold thicknesses (SFT); and FFM SDS for 4CM, DXA and bioelectrical impedance analysis (BIA; height2/Z)) in 927 subjects aged 3.8–22.0 y (211 healthy, 716 patients).
Results
DXA was the most accurate method for both FM and FFM SDS in healthy subjects and patients (mean bias (limits of agreement) FM SDS 0.03 (±0.62); FFM SDS −0.04 (±0.72)), and provided best agreement with the 4-C model in identifying abnormal BC (SDS ≤−2 or ≥2). BMI and SFTs were reasonable predictors of abnormal FM SDS, but poor in providing an absolute value. BIA was comparable to DXA for FFM SDS and in identifying abnormal subjects.
Conclusions
DXA may be used both for research and clinically to determine FM and FFM SDS. BIA may be used to assess FFM SDS in place of DXA. BMI and SFTs can be used to measure adiposity for groups but not individuals. The performance of simpler techniques in monitoring longitudinal BC changes requires investigation. Ultimately, the most appropriate method should be determined by its predictive value for clinical outcome.
doi:10.1371/journal.pone.0062139
PMCID: PMC3656861  PMID: 23690932
21.  Pre-treatment predictors of attrition in a randomised controlled trial of psychological therapy for severe and enduring anorexia nervosa 
BMC Psychiatry  2014;14:69.
Background
Attrition is common in the treatment of anorexia nervosa and its causes are complex and incompletely understood. In particular, its relationship with adaptive function and motivational stage of change has been little studied. This study aimed to (1) investigate and (2) compare the strength of associations between adaptive function, stage of change and other previously found factors such as illness sub-type and treatment attrition in women with severe and enduring anorexia nervosa (SE-AN).
Methods
Participants were 63 adult women with SE-AN of at least 7 years duration who were enrolled in a multi-site randomized controlled trial conducted from July 2007 through June 2011. Treatment comprised 30 outpatient visits over 8 months of either Cognitive Behaviour Therapy for Anorexia Nervosa (CBT-AN) or Specialist Supportive Clinical Management (SSCM) both of which were modified for severe and enduring illness. Assessments were done at baseline, end of treatment, and 6 and 12 month post treatment follow-up. Demographic variables, duration of illness, specific and generic health related quality of life (QoL), eating disorder (ED) and mood disorder symptoms, social adjustment, body mass index (BMI), and motivation for change were assessed with interview and self-report questionnaires. Treatment attrition was defined as leaving therapy after either premature termination according to trial protocol or self-instigated discharge. Binary logistic regression was used to investigate relative strength of associations.
Results
Those who did not complete treatment were significantly more likely to have the purging sub-type of anorexia nervosa and poorer ED related QoL. There were no significant differences between attrition and which therapy was received, educational level, and global ED psychopathology, stage of change, BMI, social adjustment, duration of illness or level of depression. The strongest predictors on multivariable analysis were ED QoL and AN-purging subtype.
Conclusion
This study supported previous findings of associations between attrition and purging subtype. Furthermore, we found associations between a potentially important cycle of attrition, and poorer EDQoL, which has not been previously reported. Contrary to expectations we did not find an association with BMI, severity of ED symptoms, low level of motivation to change ED features, or level of education.
doi:10.1186/1471-244X-14-69
PMCID: PMC3995934  PMID: 24606873
Anorexia nervosa; Attrition; Premature termination of treatment; Eating disorders; Dropout; Treatment
22.  A Randomized Controlled Trial of Adjunctive Family Therapy and Treatment as Usual Following Inpatient Treatment for Anorexia Nervosa Adolescents 
PLoS ONE  2012;7(1):e28249.
Research on treatments in anorexia nervosa (AN) is scarce. Although most of the therapeutic programs used in ‘real world practice’ in AN treatment resort to multidisciplinary approaches, they have rarely been evaluated.
Objective
To compare two multidimensional post-hospitalization outpatients treatment programs for adolescents with severe AN: Treatment as Usual (TAU) versus this treatment plus family therapy (TAU+FT).
Method
Sixty female AN adolescents, aged 13 to 19 years, were included in a randomized parallel controlled trial conducted from 1999 to 2002 for the recruitment, and until 2004 for the 18 months follow-up. Allocation to one of the two treatment groups (30 in each arm) was randomised. The TAU program included sessions for the patient alone as well as sessions with a psychiatrist for the patient and her parents. The TAU+FT program was identical to the usual one but also included family therapy sessions targeting intra-familial dynamics, but not eating disorder symptoms. The main Outcome Measure was the Morgan and Russell outcome category (Good or Intermediate versus Poor outcome). Secondary outcome indicators included AN symptoms or their consequences (eating symptoms, body mass index, amenorrhea, number of hospitalizations in the course of follow-up, social adjustment). The evaluators, but not participants, were blind to randomization.
Results
At 18 months follow-up, we found a significant group effect for the Morgan and Russell outcome category in favor of the program with family therapy (Intention-to-treat: TAU+FT :12/30 (40%); TAU : 5/29 (17.2%) p = 0.05; Per Protocol analysis: respectively 12/26 (46.2%); 4/27 (14.8%), p = 0.01). Similar group effects were observed in terms of achievement of a healthy weight (i.e., BMI≥10th percentile) and menstrual status.
Conclusions
Adding family therapy sessions, focusing on intra-familial dynamics rather than eating symptomatology, to a multidimensional program improves treatment effectiveness in girls with severe AN.
Trial Registration
Controlled-trials.com ISRCTN71142875
doi:10.1371/journal.pone.0028249
PMCID: PMC3251571  PMID: 22238574
23.  Reduced salience and default mode network activity in women with anorexia nervosa 
Background
The neurobiology of anorexia nervosa is poorly understood. Neuronal networks contributing to action selection, self-regulation and interoception could contribute to pathologic eating and body perception in people with anorexia nervosa. We tested the hypothesis that the salience network (SN) and default mode network (DMN) would show decreased intrinsic activity in women with anorexia nervosa and those who had recovered from the disease compared to controls. The basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated.
Methods
Between January 2008 and January 2012, women with restricting-type anorexia nervosa, women who recovered from the disease and healthy control women completed functional magnetic resonance imaging during a conditioned stimulus task. Network activity was studied using independent component analysis.
Results
We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls. Salience network activity in the anterior cingulate cortex was reduced in women with anorexia nervosa (p = 0.030; all results false-discovery rate–corrected) and recovered women (p = 0.039) compared to controls. Default mode network activity in the precuneus was reduced in women with anorexia compared to controls (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA; p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was reduced in women with anorexia compared to controls; SMN activity in the SMA (p = 0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with anorexia compared to recovered women. There were no group differences in the BGN.
Limitations
Differences between patient and control populations (e.g., depression, anxiety, medication) are potential confounds, but were included as covariates.
Conclusion
Reduced SN activity in women with anorexia nervosa and recovered women could be a trait-related biomarker or illness remnant, altering the drive to approach food. The alterations in the DMN and SMN observed only in women with anorexia nervosa suggest state-dependent abnormalities that could be related to altered interoception and body image in these women when they are underweight but that remit following recovery.
doi:10.1503/jpn.130046
PMCID: PMC3997603  PMID: 24280181
24.  Comprehensive out-patient pulmonary rehabilitation: Treatment outcomes in early and late stages of chronic obstructive pulmonary disease 
Annals of Thoracic Medicine  2011;6(2):70-76.
BACKGROUND:
The aim was to evaluate the outcomes of a comprehensive pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) and to establish whether in early disease stage PR is as effective as in late stages of disease.
METHODS:
A total of 55 stable COPD patients, 28 with early and 27 with late disease stages, were assessed. Patients underwent a comprehensive out-patient PR program for 8 weeks. To eluciate the effects of PR and compare the level of improvement; lung function, dyspnea sensation [Medical Research Council (MRC)], body composition [body mass index (BMI), fat free mass (FFM), fat free mass index (FFMI)], exercise capacity [incremental shuttle walking test, endurance shuttle walking test], health related quality of life (HRQoL) with St. George Respiratory Disease Questionnaire, psycohological status (Hospital anxiety–depression (HAD) scale) were evaluated before and after PR.
RESULTS:
At the end of PR in the early disease stage group, the improvement in forced vital capacity (FVC) reached a statistically significant level (P < 0.05). In both disease stages, there were no significant differences in BMI, FFM, and FFMI. The decrease in exertional dyspnea for the two groups evaluated with the modified BORG scale were not found statistically significant, though the dyspnea scores evaluated with MRC showed significant improvements (P < 0.001). HRQoL and exercise capacity were significantly improved for the two groups (P < 0.001). Psychological status evaluated with the HAD scale improved after PR (P < 0.001) both in early and late stages. Gainings in the study parameters did not differ in the early and the late disease stages.
CONCLUSIONS:
These results showed that patients with COPD had benefited from a comprehensive PR program in an out-patient setting regardless of disease severity. Even patients with earlier stage of disease should be referred and encouraged to participate in a PR program.
doi:10.4103/1817-1737.78420
PMCID: PMC3081559  PMID: 21572695
Chronic obstructive pulmonary disease; disease severity; functional status; pulmonary rehabilitation; shuttle walk test
25.  Differential Methylation of the Oxytocin Receptor Gene in Patients with Anorexia Nervosa: A Pilot Study 
PLoS ONE  2014;9(2):e88673.
Background and Aim
Recent studies in patients with anorexia nervosa suggest that oxytocin may be involved in the pathophysiology of anorexia nervosa. We examined whether there was evidence of variation in methylation status of the oxytocin receptor (OXTR) gene in patients with anorexia nervosa that might account for these findings.
Methods
We analyzed the methylation status of the CpG sites in a region from the exon 1 to the MT2 regions of the OXTR gene in buccal cells from 15 patients and 36 healthy women using bisulfite sequencing. We further examined whether methylation status was associated with markers of illness severity or form.
Results
We identified six CpG sites with significant differences in average methylation levels between the patient and control groups. Among the six differentially methylated CpG sites, five showed higher than average methylation levels in patients than those in the control group (64.9–88.8% vs. 6.6–45.0%). The methylation levels of these five CpG sites were negatively associated with body mass index (BMI). BMI, eating disorders psychopathology, and anxiety were identified in a regression analysis as factors affecting the methylation levels of these CpG sites with more variation accounted for by BMI.
Conclusions
Epigenetic misregulation of the OXTR gene may be implicated in anorexia nervosa, which may either be a mechanism linking environmental adversity to risk or may be a secondary consequence of the illness.
doi:10.1371/journal.pone.0088673
PMCID: PMC3921190  PMID: 24523928

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