Chronic Anorexia Nervosa Research Articles

Comparing hospitalized adult patients with chronic anorexia nervosa with versus without prior hospitalizations

BackgroundAnorexia nervosa (AN) is a severe psychiatric disorder, from which recovery is often protracted. The role of prior specialized inpatient treatment on subsequent treatment attempts for adults with chronic AN and predictors of treatment response for severe and enduring AN (SE-AN) are needed to improve outcomes.MethodParticipants (N = 135) with chronic AN (ill ≥7 years) admitted to an integrated inpatient-partial hospitalization eating disorders (ED) unit with prior ED hospitalization(s) (+ PH; n = 100) were compared to those without prior ED hospitalizations (-PH; n = 35) on admission characteristics (BMI, length of illness, outpatient ED treatment history, symptomatology (ED, anxiety, and depressive), history of suicide attempts or non-suicidal self-injury (NSSI)), treatment motivation and recovery self-efficacy, and discharge outcomes (discharge BMI, rate of weight gain, length of stay, clinical improvement).ResultsGroups were similar with regard to age, years ill, and admission BMI. The + PH group had lower desired weight, lifetime nadir BMI and self-efficacy for normative eating, and higher state and trait anxiety than the -PH group. +PH were also more likely to endorse history of NSSI and suicide attempt. Regarding discharge outcomes, most patients achieved weight restoration at program discharge (mean discharge BMI = 19.8 kg/m2). Groups did not differ on rate of weight gain, likelihood of attending partial hospital, partial hospital length of stay, program discharge BMI, or likelihood of clinical improvement (p’s > 0.05) although inpatient length of stay was longer for the + PH group.ConclusionsParticipants with chronic AN + PH exhibited more severe psychiatric comorbidity and lower self-efficacy for normative eating than AN -PH, however short-term discharge outcomes were similar. Future research should determine whether weight restoration and targeting comorbidities impacts relapse risk or need for rehospitalization among chronic and severe + PH. Despite similar illness durations, those with chronic AN -PH may be able to transition to partial hospital earlier. Conversely there is risk of undertreatment of chronic AN + PH given the recent shift promoting briefer self-directed admissions for adults with SE-AN. Research comparing + PH and -PH adults with chronic AN may facilitate efforts to individualize care and characterize relapse risk following intensive treatment.

Changes in the Firmicutes to Bacteriodetes ratio in the gut microbiome in individuals with anorexia nervosa following inpatient treatment: A systematic review and a case series.

Anorexia nervosa has the highest mortality rate among psychiatric illnesses. Current treatments remain ineffective for a large fraction of patients. This may be due to unclear mechanisms behind its development and maintenance. Studies exploring the role of the gut microbiome have revealed inconsistent evidence of dysbiosis. This article aims to investigate changes in the gut microbiome, particularly, mean differences in the Firmicutes to Bacteroidetes ratio, in adolescent and adult individuals with anorexia nervosa following inpatient treatment. Longitudinal studies investigating gut microbiome composition in inpatient populations of anorexia nervosa before and after treatment were systematically reviewed. Additionally, gut microbiome compositions were characterized in three acute anorexia nervosa inpatients early after admission and after 4-12weeks of treatment. Review results indicated an increase in the Firmicutes to Bacteroidetes ratio in individuals with anorexia nervosa after treatment. These however did not match values of their healthy counterparts. In the case-series samples, the reverse occurred with samples taken 4weeks after treatment. In the patient who provided an extra sample 12weeks after treatment, similar results to the studies included in the review were observed. Furthermore, Firmicutes to Bacteroidetes ratio values in the case-series samples were notably higher in the two patients who had chronic anorexia nervosa. Differences in methodologies, small sample sizes, and insufficient data limited the generalizability of the outcomes of the reviewed studies. Results suggest a potentially unique microbiome signature in individuals with chronic anorexia nervosa, which may explain different outcomes in this group of patients.

Older adult women with chronic anorexia nervosa: heterogeneous adaptation to undernutrition over time.

Anorexia nervosa (AN) in older adult women is primarily described through reviews or case reports focusing on psychiatric traits, with no comprehensive studies evaluating their complete nutritional and hormonal profiles. This study aimed to describe a group of women with anorexia nervosa aged above 35 years old (AN35), and compare them with young women with anorexia nervosa (ANY) and normal-weight control participants. Anthropometric, metabolic, nutritional, and psychiatric parameters were collected and compared among three groups of women: 50 AN35, 37 ANY, and 38 controls. AN35 exhibited a mean disease duration of 271 ± 19 months, with 94% chronic forms and 58% restrictive types. Despite having similar BMI as ANY, AN35 displayed more altered parameters, including higher liver enzymes (p = 0.007), free T3 (p = 0.0046) and leptin (p < 0.0001); and lower albumin (p = 0.0029), and white cells (p < 0.0001). AN35 showed significant heterogeneity in hormonal adaptation, such as free T3. Half of the patients aged above 51 years revealed high gonadotropin levels despite being undernourished. Additionally, AN35 groups presented with 50% of bones fractures, decreased T-scores under -2.5 (p < 0.0001 for femoral), and altered micro architectural HRPQT parameters compared to ANY. Anorexia nervosa in older adult women is predominantly chronic. Nutritional parameters changes with age suggests a significant heterogeneity and possible adaptation of energy balance and bodyweight set point for others. Complications may be severe, altering the quality of life, and sometimes potentially lethal. These findings highlight the potential adaptation of energy balance with age, and should assist clinicians in clinical practice.

Pediatric early-phase anorexia nervosa without hypokalemia exhibiting acute tubular injury: a case report.

Anorexia nervosa can lead to kidney complications. Few studies reported kidney biopsy results in young adults, most of whom had chronic anorexia nervosa, and kidney biopsy findings in pediatric patients with early-phase anorexia nervosa are rarely reported. A 14-year-old girl who lost weight due to excessive exercise and reduced diet was admitted for kidney dysfunction. She was 147cm tall and weighed 32.9kg, with a body mass index of 15.2kg/m2. She was 39kg about a year earlier. Her heart rate and blood pressure were 30-40 beats/min and 108/68mmHg, respectively. She had kidney dysfunction (estimated glomerular filtration rate, 56.6mL/min/1.73 m2). Urine β2-microglobulin was slightly elevated (393μg/L), and percent tubular phosphate reabsorption was low (75.2%), suggesting tubular damage; however, hypokalemia was absent. Kidney dysfunction did not improve with fluid loading. Kidney biopsy revealed that all glomeruli were intact, with no vasculitis, interstitial inflammation or fibrosis on light microscopy. However, proximal tubular epithelial walls were flattened and the brush border was absent, suggesting acute tubular injury. Immunofluorescent staining was negative for immunoglobulins and complement proteins, and electron microscopy showed no significant electron-dense deposition. The patient's serum creatinine gradually declined, normalizing on the 17th day of admission. Unlike previous reports in young adults, kidney dysfunction was observed even in the absence of hypokalemia in the current pediatric patient with early-phase anorexia nervosa. Proximal tubular injury in early-phase anorexia nervosa may be caused by bradycardia without hypokalemia, leading to subsequent kidney dysfunction.

Redefining Anorexia Nervosa and Its Causes to Rethink Its Care

Described by the physicians Charles Lasègue and William Gull in two independent papers published in 1873, the conceptual birth of the diagnosis of anorexia nervosa is now 150 years old. The etiological quest of the past decades has been unsuccessful while epistemologically the definition of anorexia has continued to vary. The aim of this article is therefore twofold: to open up new avenues of reflection (a) by proposing a “sociopsychobiological” redefinition of anorexia nervosa by integrating a teleological perspective and (b) by questioning its current management, in particular the possible iatrogenic nature of care. Thus, we define anorexia nervosa here as any behavior in an individual who, when confronted with an existential problem, finds a solution by engaging in a quest for lightness, which can gradually become uncontrollable and lead to death from malnutrition. It is therefore pathological intentionality—pathological because it is uncontrollable—that constitutes the core of anorexia nervosa as a disorder. In the hospital context, this pathological intentionality clashes with the intentionality of the carers. Concerning the cared-for, I highlight the iatrogenic risk of caring for patients suffering from chronic and severe anorexia nervosa. If the locus of pathology is the intention of the subject, then any context of medical care that reinforces the vehemence of that intention is likely to be iatrogenic. This potential iatrogenic effect is of a very particular nature since it intrinsically reinforces the pathology. This concept of collision of intentions can lead to the development of new epistemological thinking, an argument for highlighting the iatrogenic risk of medical care and a plea for care that generates less suffering for both carers and the cared-for.

Establishment of a Murine Chronic Anorexia Nervosa Model.

Anorexia nervosa (AN) is associated with hyperactivity, amenorrhea, and brain atrophy. The underlying pathophysiology is mostly unknown, and new targets for therapeutic interventions are needed. This study aimed to systematically establish a murine AN model with the parameter extent of starvation, animal age, and length of starvation for functional studies. The activity-based anorexia (ABA) model combines food restriction with running wheel access. Early adolescent and adolescent mice received 40% of their baseline food intake until a 20% or 25% weight reduction was reached (acute starvation). To mimic chronic starvation, body weight loss was maintained for another two weeks. Running activity was examined using wheel sensors, while amenorrhea was investigated by analysis of vaginal smears. Brain sections were used to analyze cerebral cortex volumes. Acute starvation did not lead to either AN-related symptoms, whereas chronic starvation led to hyperactivity and amenorrhea except in the adolescent cohort with 20% weight reduction. Only ABA mice with 25% weight reduction revealed a cortex volume reduction. The optimal parameters to mirror AN-related symptoms included a 25% weight reduction, early adolescent or adolescent mice, and chronic starvation. The ABA model enables functional analysis of the impact of chronic AN on the underlying hormonal, behavioral, and brain pathophysiology.

Restlessness and an Increased Urge to Move (Drive for Activity) in Anorexia Nervosa May Strengthen Personal Motivation to Maintain Caloric Restriction and May Augment Body Awareness and Proprioception: A Lesson From Leptin Administration in Anorexia Nervosa.

Anorexia nervosa (AN), a disorder of voluntary food restriction leading to severe weight loss in female adolescents, remains an enigma. In particular, the appropriation of the starved thin body into the self-concept in AN is a process insufficiently researched and still poorly understood. Healthy humans undergoing starvation experience a slowing of movements and avoid voluntary exercise. By contrast, AN tends to be not infrequently associated with voluntary, sometimes excessive and/or compulsive exercise. Such deliberate exercise, not reported in starvation, seems to be facilitated by an increased urge for movement and physical restlessness, particular to AN. The increased urge to move would reflect spontaneous daily activity, the energy expended for everything that is not sleeping, eating, or voluntary exercise. Our hypothesis is that the starvation-induced increased urge to move and restlessness may promote the development of AN. Reversal of the fasting state, by either high caloric food or by leptin administration, would be expected to reduce restlessness and the increased urge to move along with improvement in other symptoms in AN. This review explores the idea that such restless activation in AN, in itself and through accelerating body weight loss, might foster the integration of the starving body into the self-concept by (1) enhancing the person’s sense of self-control and sense of achievement and (2) through invigorating proprioception and through intensifying the perception of the changing body shape. (3) Tentative evidence from studies piloting leptin administration in chronic AN patients which support this hypothesis is reviewed. The findings show that short term administration of high doses of leptin indeed mitigated depressive feelings, inner tension, intrusive thoughts of food, and the increased urge to be physically active, easing the way to recovery, yet had little influence on the patients’ personal commitment to remain at a low weight. Full recovery then requires resolution of the individuals’ personal unresolved psychological conflicts through psychotherapy and frequently needs specialized treatment approaches to address psychiatric co-morbidities. AN might be conceptualized as a hereditary form of starvation resistance, facilitated by the effects of starvation on fitness allowing for an exceptionally intense personal commitment to perpetuate food restriction.

Evidence for correlations between BMI-associated SNPs and circRNAs

Circular RNAs (circRNAs) are regulators of processes like adipogenesis. Their expression can be modulated by SNPs. We analysed links between BMI-associated SNPs and circRNAs. First, we detected an enrichment of BMI-associated SNPs on circRNA genomic loci in comparison to non-significant variants. Analysis of sex-stratified GWAS data revealed that circRNA genomic loci encompassed more genome-wide significant BMI-SNPs in females than in males. To explore whether the enrichment is restricted to BMI, we investigated nine additional GWAS studies. We showed an enrichment of trait-associated SNPs in circRNAs for four analysed phenotypes (body height, chronic kidney disease, anorexia nervosa and autism spectrum disorder). To analyse the influence of BMI-affecting SNPs on circRNA levels in vitro, we examined rs4752856 located on hsa_circ_0022025. The analysis of heterozygous individuals revealed an increased level of circRNA derived from the BMI-increasing SNP allele. We conclude that genetic variation may affect the BMI partly through circRNAs.

Association of gut-specific non-inflammatory T lymphocytes with chronic anorexia nervosa and constitutional thinness.

Previous studies of AN showed low-grade inflammation. Are low-grade inflammation and circulating lymphocytes associated with chronic conditions? Peripheric blood cytokines were measured using Luminex™ technology in a chronic AN cohort (mean=67.42months), compared to Constitutional Thinness (CT), Constitutional Obesity (CO), and Healthy Controls (HC). Secondarily a prospective cohort of chronic AN (mean=54.11months) was recruited to compare the functional lymphocyte profile in blood by flow cytometry to CT and HC. In the AN group, most cytokine concentrations were lower than in CT and HC groups. The IL-23 (98.02 pg/ml) was elevated related to HC and CO, and the IL-10 (4.178 pg/ml) was elevated versus CO. In the CT group, IL-9 (0.06216 pg/ml) was elevated compared to AN. The AN group had high Treg (9.259% of CD4+ ) and CD8+ Integrinβ7+ (9.552% of CD3+ ) versus HC for lymphocyte populations. In CT group, elevated Treg (9.7% of CD4+ ) elevated percentage of CD4+ CCR9+ (5.867% of CD3+ ) and CD8+ Integrinβ7+ (10.21% of CD3+ ) were found versus HC. The chronic state of AN and CT is surprisingly non-inflammatory with elevated Treg cells. These results suggest that maintaining a dysregulated response to intestinal antigens may contribute to maintaining AN.

Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa.

Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.

A Perspective on Chronic and Long-Lasting Anorexia Nervosa.

Anorexia Nervosa (AN) is a severe eating disorder which typically develops in younger females. Many studies focus on this specific population, a majority of which will eventually partially or fully recover. A minority will become chronic despite extensive treatment. These patients are treatment-resistant and may not necessarily benefit from usual treatment. In this article we will reflect on possible mechanisms which may explain the maintenance of disease, and especially on the possible role of affective and anxiety disturbances. We will use, due to the lack of large-scale studies, data from risk and prognostic factors, treatment options and neurobiological correlates in chronic AN patients. Lastly, we will propose how these elements may advise further research and treatments.

Five-year mortality of severely malnourished patients with chronic anorexia nervosa admitted to a medical unit.

Anorexia nervosa (AN) is associated with one of the highestmortalityrates of any psychiatric disorder but limited mortality data were reported for those with extremely severe malnutrition. This study aimed to estimate standardizedmortalityratio (SMR), investigate predictive factors of mortality and causes of death among a sample of patients with AN admitted to a specialized clinical nutrition unit (CNU) because of extremely severe malnutrition. Between 11/27/1997 and 01/15/2014, vital status was determined for 384 patients admitted for AN at the first time in the CNU. Sociodemographic, anamnestic, and clinical data were collected. We calculated the SMR. Univariate and multivariate Cox regression analyses were performed to identify mortality predictors. Crude mortality rate was 11.5%. (44 deaths) and SMR 15.9 [CI 95% (11.6-21.4)], 5.2years post inpatient treatment. Mortality predictors at the time of hospitalization were as follows: older age, occurrence of an in-hospital suicide attempt, transfer to medical intensive care unit and the following somatic complications: frank anemia, dysnatremia, infectious and cardiac complications. Other predictors of mortality were: past or present history of discharge against medical advice, hematological comorbidities (not related to AN). A longer inpatient length of stay was a protective factor. Very severely malnourished patients with AN hospitalized in a medical unit because of extremely severe somatic issues have a medium-term mortality rate higher than the general population and even higher than patients in tertiary specialized ED units. This study highlights predictive factors of mortality that will help clinicians in recognizing and managing patients at risk of death.

Chronic anorexia nervosa: Patient characteristics and treatment approaches.

Anorexia nervosa constitutes amajor challenge to medical practitioners, especially clinicians, due to a high rate of chronicity and a very serious risk of relapse. One of the underlying causes of this state of affairs is the ego-syntonicity of the disorder, which differentiates it from similar conditions, and which is responsible for the patient's denial and lack of motivation for treatment (resulting in frequent instances of therapy refusal or drop-out). The paper outlines different approaches to defining chronic anorexia nervosa. Thisform of anorexia and its therapeutic implications are discussed through the lens of clinicians and other medical professionals. Furthermore, the patients'experiences of chronic anorexia nervosa are described. The dilemmas concerning palliative care for this group of patients are addressed and treatment options and relapse prevention strategies are recommended, with a focus on the latest developments in this respect. The paper is concluded with an optimistic report of complete recovery from this diagnosis, including an analysis of the factors underlying the positive therapeutic outcome.

A Randomized Trial of Deep Brain Stimulation to the Subcallosal Cingulate and Nucleus Accumbens in Patients with Treatment-Refractory, Chronic, and Severe Anorexia Nervosa: Initial Results at 6 Months of Follow Up

Background: The main objective of this study was to assess the safety and efficacy of deep brain stimulation (DBS) in patients with severe anorexia nervosa (AN). Methods: Eight participants received active DBS to the subcallosal cingulate (SCC) or nucleus accumbens (NAcc) depending on comorbidities (affective or anxiety disorders, respectively) and type of AN. The primary outcome measure was body mass index (BMI). Results: Overall, we found no significant difference (p = 0.84) between mean preoperative and postoperative (month 6) BMI. A BMI reference value (BMI-RV) was calculated. In patients that received preoperative inpatient care to raise the BMI, the BMI-RV was defined as the mean BMI value in the 12 months prior to surgery. In patients that did not require inpatient care, the BMI-RV was defined as the mean BMI in the 3-month period before surgery. This value was compared to the postoperative BMI (month 6), revealing a significant increase (p = 0.02). After 6 months of DBS, five participants showed an increase of ≥10% in the BMI-RV. Quality of life was improved (p = 0.03). Three cases presented cutaneous complications. Conclusion: DBS may be effective for some patients with severe AN. Cutaneous complications were observed. Longer term data are needed.

Self‐defining memories in female patients with anorexia nervosa

Overgeneral autobiographical memory (AM) was reported in patients with anorexia nervosa (AN) using AM cueing tasks that did not directly indexes memories that are personally important to the individual, that is, self-defining memories (SDMs). The aim of this study is to investigate characteristics of SDMs in females with AN. A total of 46 outpatients with chronic AN and 52 healthy controls (HC) were asked to recall three SDMs. Compared to HC, patients with AN presented less specific SDMs, but have preserved ability to give meaning to their memories. Patients' SDMs were associated with more negative emotions, more tension (i.e. explicit expression of discomfort, disagreement or unease) and more contamination (i.e. transformation in the memory narrative from a positive to a negative affective state). Content of SDMs differed between patients with AN and HC. Finally, no difference was found in SDMs characteristics between the two subtypes of anorexia nervosa (restricting type and binge eating / purging type). Patients with AN recalled overgeneral SDMs with negative content and emotions. In this context, a clinical intervention based on SDMs together with cognitive and emotional remedial therapies could help patients with AN to improve emotion processing and redefine their identity in a more positive way.

Acute Abdomen in Chronic Anorexia Nervosa with Episodes of Bulimia.

Acute Abdomen in Chronic Anorexia Nervosa with Episodes of Bulimia.

Harm minimization in severe and enduring anorexia nervosa

For many sufferers of anorexia nervosa, the time course is long, and the prospect of disability and family burden great. This is all too often the case, even with early diagnosis and treatment. The term severe and enduring anorexia nervosa has been applied to these survivors. Yet, a majority of patients do eventually recover and, even where this is not the case, adaptive medical stability and function can be maintained despite alarming dilapidation. Managing the years of illness so as to have the best outcome physically and psychologically, even where full weight recovery does not occur, or has not yet occurred, is the topic of this article. Literature pertaining to harm minimization in chronic, severe, enduring, and long-standing anorexia nervosa was selectively reviewed using an Ovid data base and Google Scholar. The authors’ own clinical experience over almost four decades in public and private hospital and community settings has also informed much of what has been written. The authors would like to think that it is possible to do better than the familiar injunction (variously attributed to Hippocrates, Galen, and others) of ‘primum non nocere’—although this is a good place to start.

Decline of Plasma Concentrations of Interleukin-18 in Severely Malnourished Patients with Anorexia Nervosa: Exploratory Analysis.

Multiple studies on the dynamics of inflammatory cytokines in patients with anorexia nervosa (AN) have been published, although results are not consistent among reports. Thus the pathophysiologic roles of these cytokines are not clear. We performed an exploratory analysis that included (1) comparisons of plasma interleukin-18 (IL-18) concentrations between patients with AN (n = 21) and healthy controls (n = 39), and (2) correlations between body mass index (BMI) and IL-18 concentrations in both groups, exploring the relationship between malnourishment and IL-18. Plasma IL-18 levels were significantly decreased in patients with AN compared with controls. Plasma IL-18 levels correlated to BMI in controls, but not in patients with AN. These results suggest that a decline in plasma IL-18 levels in patients with AN is not only due to malnourishment, but other pathophysiologic changes as well. IL-18 has a role in the brain’s reaction to sadness and chronic stress. Therefore, decreased levels of IL-18 may commonly occur in patients with chronic AN.

Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial

Anorexia nervosa is a life-threatening illness. Brain circuits believed to drive anorexia nervosa symptoms can be accessed with surgical techniques such as deep brain stimulation (DBS). Initial results suggest that DBS of the subcallosal cingulate is safe and associated with improvements in mood and anxiety. Here, we investigated the safety, clinical, and neuroimaging outcomes of DBS of the subcallosal cingulate in a group of patients during 12 months of active stimulation. We did this prospective open-label trial at the Department of Surgery of the University of Toronto (Toronto, ON, Canada). Patients were eligible to participate if they were aged 20-60 years and had a diagnosis of anorexia nervosa (restricting or binge-purging subtype) and a demonstrated history of chronicity or treatment resistance. Following a period of medical stabilisation, patients underwent surgery for DBS and received open-label continuous stimulation for the entire 1 year study duration. The primary outcome was safety and acceptability of the procedure. The secondary outcomes were body-mass index (BMI), mood, anxiety, affective regulation, and anorexia nervosa-specific behaviours at 12 months after surgery, as well as changes in neural circuitry (measured with PET imaging of cerebral glucose metabolism at baseline and at 6 and 12 months after surgery). This trial was registered with ClinicalTrials.gov, number NCT01476540. 16 patients with treatment-refractory anorexia nervosa were enrolled between September, 2011, and January, 2014, and underwent DBS of the subcallosal cingulate between November, 2011, and April, 2014. Patients had a mean age of 34 years (SD 8) and average illness duration of 18 years (SD 6). Two patients requested that their devices be removed or deactivated during the study, although their reasons for doing so were poorly defined. The most common adverse event was pain related to surgical incision or positioning that required oral analgesics for longer than 3-4 days after surgery (five [31%] of 16 patients). Seven (44%) of 16 patients had serious adverse events, most of which were related to the underlying illness, including electrolyte disturbances. Average BMI at surgery was 13·83 (SD 1·49) and 14 (88%) of the 16 patients had comorbid mood disorders, anxiety disorders, or both. Mean BMI after 12 months of stimulation was 17·34 (SD 3·40; p=0·0009 vs baseline). DBS was associated with significant improvements in measures of depression (mean Hamilton Depression Rating Scale scores 19·40 [SD 6·76] at baseline vs 8·79 [7·64] at 12 months; p=0·00015), anxiety (mean Beck Anxiety Inventory score 38·00 [15·55] vs 27·14 [18·39]; p=0·035), and affective regulation (mean Dysfunction in Emotional Regulation Scale score 131·80 [22·04] vs 104·36 [31·27]; p=0·019). We detected significant changes in cerebral glucose metabolism in key anorexia nervosa-related structures at both 6 months and 12 months of ongoing brain stimulation. In patients with chronic treatment-refractory anorexia nervosa, DBS is well tolerated and is associated with significant and sustained improvements in affective symptoms, BMI, and changes in neural circuitry at 12 months after surgery. Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research.

Affective Responses in Different Stages of Anorexia Nervosa: Results from a Startle-reflex Paradigm.

There is an evolving debate about pathological affective responses in patients with anorexia nervosa (AN). We examined startle responses in different stages of AN. We applied a startle reflex paradigm with standardized visual stimuli (International Affective Pictures System; food and body pictures) in 64 female participants (17 acute AN, 16 chronically ill AN, 15 long-term recovered AN, 16 healthy controls). We measured subjective ratings of valence and anxiety, and electromyographic startle responses. Participants with acute and chronic AN displayed the same subjective valence ratings to affective stimuli but showed less startle reactivity to affective pictures (F(6, 116) = 2.75, p = .02) compared with healthy control. Food pictures were rated as more unpleasant and higher anxiety provoking by currently ill AN (F(3, 59) = 3.32, p=.03). We observed diverging subjective and psychophysiological reactions in different stages of AN. Psychophysiological methods can help to attain a more comprehensive understanding of biological alterations in the long-term course of AN. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.