Cancer Incidence among Patients with Anorexia Nervosa from Sweden,Denmark and Finland

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis.     

Saccadic Eye Movements in Anorexia Nervosa

Background

Anorexia Nervosa (AN) has a mortality rate among the highest of any mental illness, though the factors involved in the condition remain unclear. Recently, the potential neurobiological underpinnings of the condition have become of increasing interest. Saccadic eye movement tasks have proven useful in our understanding of the neurobiology of some other psychiatric illnesses as they utilise known brain regions, but to date have not been examined in AN. The aim of this study was to investigate whether individuals with AN differ from healthy individuals in performance on a range of saccadic eye movements tasks.

Methods

24 females with AN and 25 healthy individuals matched for age, gender and premorbid intelligence participated in the study. Participants were required to undergo memory-guided and self-paced saccade tasks, and an interleaved prosaccade/antisaccade/no-go saccade task while undergoing functional magnetic resonance imaging (fMRI).

Results

AN participants were found to make prosaccades of significantly shorter latency than healthy controls. AN participants also made an increased number of inhibitory errors on the memory-guided saccade task. Groups did not significantly differ in antisaccade, no-go saccade or self-paced saccade performance, or fMRI findings.

Discussion

The results suggest a potential role of GABA in the superior colliculus in the psychopathology of AN.     

The Endocrinopathies of Anorexia Nervosa

ObjectiveTo describe the hormonal adaptations and alterations in anorexia nervosa.MethodsWe performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings.ResultsAnorexia nervosa is a devastating disease with a variety of endocrine manifestations. The effects of starvation are extensive and negatively affect the pituitary gland, thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. A thorough understanding of refeeding syndrome is imperative to nutrition rehabilitation in these patients to avoid devastating consequences. Although most endocrinopathies associated with anorexia nervosa reverse with recovery, short stature, osteoporosis, and infertility may be long-lasting complications. We describe a 20-year-old woman who presented with end-stage anorexia nervosa whose clinical course reflects the numerous complications caused by this disease.ConclusionsThe effects of severe malnutrition and subsequent refeeding are extensive in anorexia nervosa. Nutrition rehabilitation is the most appropriate treatment for these patients; however, it must be done cautiously. (Endocr Pract. 2008;14:1055-1063)     

Acute Gastric Dilatation in Anorexia Nervosa

Two patients with anorexia nervosa were treated on a general surgical unit for acute gastric dilatation. In both cases the dilatation rapidly followed an increase in the usual low dietary intake of the patients, and the ingestion of extra food may have initiated the acute episode. Conservative treatment with parenteral fluids, nasogastric intubation, and then a gradual return to a normal diet proved a satisfactory method of management. In one patient the anorexia itself was improved.     

Anorexia Nervosa: The Diagnosis

This paper argues that there is a relationship between understandings of anorexia nervosa (AN) and how the ethical issues associated with involuntary treatment for AN are identified, framed, and addressed. By positioning AN as a construct/discourse (hereinafter “AN: the diagnosis”) several ethical issues are revealed. Firstly, “AN: the diagnosis” influences how the autonomy and competence of persons diagnosed with AN are understood by decision-makers in the treatment environment. Secondly, “AN: the diagnosis” impacts on how treatment and treatment efficacy are defined and the ethical justifiability of paternalism. Thirdly, “AN: the diagnosis” can limit the opportunity for persons with AN to construct an identity that casts them as a competent person. “AN: the diagnosis” can thus inherently affirm professional knowledge and values. Postmodern professional ethics can support professionals in managing these issues by highlighting the importance of taking responsibility for professional knowledge, values, and power and embracing moral uncertainty.     

Altered Mitochondrial Function and Oxidative Stress in Leukocytes of Anorexia Nervosa Patients

Context

Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress.

Objective

The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated.

Design and setting

A multi-centre, cross-sectional case-control study was performed.

Patients

Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women.

Main outcome measures

Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells.

Results

Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O₂ consumption (P<0.05), mitochondrial membrane potential (P<0.01) and GSH levels (P<0.05), and an increase in ROS production (P<0.05) with respect to control subjects. Furthermore, a reduction of mitochondrial mass was detected in leukocytes of the anorexic patients (P<0.05), while the activity of mitochondrial complex I (P<0.001), but not that of complex III, was found to be inhibited in the same population.

Conclusions

Oxidative stress is produced in the leukocytes of anorexic patients and is closely related to mitochondrial dysfunction. Our results lead us to propose that the oxidative stress that occurs in anorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.     

Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis

Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.     

Affiliative Behaviour and Conflictual Communication during Brief Family Therapy of Patients with Anorexia Nervosa

Objective

Although patients with anorexia nervosa (AN) present positive responses to family therapy, the key features of therapeutic changes still require identification. This study explores the role of conflictual communication and affiliative nonverbal behaviour in therapeutic change in brief strategic family therapy (BSFT) for AN patients.

Methods

Ten female AN patients and their parents were included in the sample and took part in a 6-month follow-up of BSFT. The durations of conflictual communication and of affiliative nonverbal behaviour estimated by eye contact were compared between the first and the last sessions of family-based treatment using nonparametric statistical tests.

Results

An increase of the Body Mass Index associated with an increase in the conflictual communication expressed during BSFT sessions were observed. Moreover, affiliative nonverbal behaviour expressed by the father and the patient decrease, after a BSFT follow-up, in conflictual situations only. By contrast, no significant difference was observed in affiliative nonverbal behaviour expressed by the mother.

Conclusion

The present study demonstrates that the impact of the BSFT differs between members of a family: the AN patient and the father have established a new form of emotional functioning with a decrease in emotional involvement. The study of the combination between verbal and nonverbal communication can represent an important step in the understanding of the mechanisms of therapeutic change.     

Dysbiosis in the Gut Bacterial Microbiome of Patients with Uveitis,an Inflammatory Disease of the Eye

Uveitis (UVT), an inflammatory disease of the eye significantly contributes to vision impairment and blindness. Uveitis is associated with systemic infectious and autoimmune diseases, but in most cases, the aetiology remains unidentified. Dysbiosis in the gut microbiome has been implicated in autoimmune diseases, inflammatory diseases, cancers and mental disorders. In a mice model of autoimmune UVT, it was observed that manipulating the gut microbiome reduces the inflammation and disease severity. Further, alterations in the bacterial gut microbiome and their metabolites were reported in UVT patients from a Chinese cohort. Hence, it is worth comparing the bacterial gut microbiome of UVT patients with that of healthy controls (HC) to ascertain whether dysbiosis of the gut microbiome has implications in UVT. Our analyses showed reduced diversity of several anti-inflammatory organisms including Faecalibacterium, Bacteroides, Lachnospira, Ruminococcus and members of Lachnospiraceae and Ruminococcaceae families, and enrichment of Prevotella (proinflammatory) and Streptococcus (pathogenic) OTUs in UVT microbiomes compared to HC. In addition, decrease in probiotic and antibacterial organisms was observed in UVT compared to HC microbiomes. Heatmap and PCoA plots also indicated significant variations in the microbiomes of UVT versus HC. This is the first study demonstrating dysbiosis in the gut bacterial communities of UVT patients in an Indian cohort and suggests a role of the gut microbiome in the pathophysiology of UVT.     

Disruption of Spatial Task Performance in Anorexia Nervosa

In anorexia nervosa (AN), body distortions have been associated with parietal cortex (PC) dysfunction. The PC is the anatomical substrate for a supramodal reference framework involved in spatial orientation constancy. Here, we sought to evaluate spatial orientation constancy and the perception of body orientation in AN patients. In the present study, we investigated the effect of passive lateral body inclination on the visual and tactile subjective vertical (SV) and body Z-axis in 25 AN patients and 25 healthy controls. Subjects performed visual- and tactile-spatial judgments of axis orientations in an upright position and tilted 90° clockwise or counterclockwise. We observed a significant deviation of the tactile and visual SV towards the body (an A-effect) under tilted conditions, suggesting a multisensory impairment in spatial orientation. Deviation of the Z-axis in the direction of the tilt was also observed in the AN group. The greater A-effect in AN patients may reflect reduced interoceptive awareness and thus inadequate consideration of gravitational inflow. Furthermore, marked body weight loss could decrease the somatosensory inputs required for spatial orientation. Our study results suggest that spatial references are impaired in AN. This may be due to particular integration of visual, tactile and gravitational information (e.g. vestibular and proprioceptive cues) in the PC.