Anorexia nervosa is an important cause of physical and psychosocial morbidity. Recent years have brought advances in understanding of the underlying psychobiology that contributes to illness onset ...and maintenance. Genetic factors influence risk, psychosocial and interpersonal factors can trigger onset, and changes in neural networks can sustain the illness. Substantial advances in treatment, particularly for adolescent patients with anorexia nervosa, point to the benefits of specialised family-based interventions. Adults with anorexia nervosa too have a realistic chance of achieving recovery or at least substantial improvement, but no specific approach has shown clear superiority, suggesting a combination of re-nourishment and anorexia nervosa-specific psychotherapy is most effective. To successfully fight this enigmatic illness, we have to enhance understanding of the underlying biological and psychosocial mechanisms, improve strategies for prevention and early intervention, and better target our treatments through improved understanding of specific disease mechanisms.
The stress response is an essential mechanism for maintaining homeostasis, and its disruption is implicated in several psychiatric disorders. On the cellular level, stress activates, among other ...mechanisms, autophagy that regulates homeostasis through protein degradation and recycling. Secretory autophagy is a recently described pathway in which autophagosomes fuse with the plasma membrane rather than with lysosomes. Here, we demonstrate that glucocorticoid-mediated stress enhances secretory autophagy via the stress-responsive co-chaperone FK506-binding protein 51. We identify the matrix metalloproteinase 9 (MMP9) as one of the proteins secreted in response to stress. Using cellular assays and in vivo microdialysis, we further find that stress-enhanced MMP9 secretion increases the cleavage of pro-brain-derived neurotrophic factor (proBDNF) to its mature form (mBDNF). BDNF is essential for adult synaptic plasticity and its pathway is associated with major depression and posttraumatic stress disorder. These findings unravel a cellular stress adaptation mechanism that bears the potential of opening avenues for the understanding of the pathophysiology of stress-related disorders.
Eating disorders (EDs) are serious mental illnesses that can be life-threatening. Stage of illness models and early intervention strategies could be informed by a better understanding of ...symptomatology that precedes the onset of an ED. This review aims to explore which symptoms (both ED and other psychiatric disorder-related) exist prior to the onset of an ED and whether there any prospective associations between these symptomatologies.
A systematic literature review was conducted in MEDLINE, Embase, and PsycINFO for large, longitudinal, prospective studies in nonclinical cohorts of children/adolescents that report symptoms prior to the onset of an ED. A quality assessment of included studies was conducted using the Newcastle-Ottawa Quality Assessment Scale.
A total of 22 studies were included, and over half were assessed to be of good quality. Studies identified the presence of a broad range of ED and other psychiatric disorder-related symptoms prior to ED onset. Possible prospective associations were identified, including early eating and feeding difficulties in childhood, to ED-related symptoms (e.g., dieting and body dissatisfaction) and other psychiatric disorder-related symptoms (e.g., anxiety and depression) in childhood/early adolescence, progressing to severe symptomatology (e.g., extreme weight control behaviors and self-harm) in mid-adolescence/emerging adulthood.
The trajectory of symptoms identified to precede and possibly predict onset of an ED may inform early intervention strategies within the community. Suggestions for further research are provided to establish these findings and the clinical implications of these discussed, in order to inform how best to target prodromal stages of EDs.
Self-Help Treatment of Eating Disorders Yim, See Heng; Schmidt, Ulrike
Psychiatric clinics of North America/The Psychiatric clinics of North America,
06/2019, Volume:
42, Issue:
2
Journal Article
Peer reviewed
Open access
The authors provide an overview of the current state of research on self-help interventions for eating disorders. The efficacy of different forms of self-help interventions for bulimia nervosa, binge ...eating disorder, and other eating disorders at various stages of the care pathway (from prevention to relapse prevention) is described. Cost-effectiveness studies are also presented. Moderators of outcome, such as guidance and adherence, are discussed. Overall, the findings are promising and support the use of self-help interventions in the treatment of bulimic disorders, across the stages of the care pathway. Less is known about the use of self-help in anorexia nervosa.
Several initiatives at establishing a classification of inherited metabolic disorders have been published previously, some focusing on pathomechanisms, others on clinical manifestations, while yet ...another attempted a simplified approach of a comprehensive nosology. Some of these classifications suffered from shortcomings, such as lack of a mechanism for continuous update in light of a rapidly evolving field, or lack of widespread input from the metabolic community at large. Our classification—the International Classification of Inherited Metabolic Disorders, or International Classification of Inborn Metabolic Disorders (ICIMD)—includes 1450 disorders, and differs from prior approaches in that it benefited from input by a large number of experts in the field, and was endorsed by major metabolic societies around the globe. Several criteria such as pathway involvement and pathomechanisms were considered. The main purpose of the hierarchical, group‐based approach of the ICIMD is an improved understanding of the interconnections between many individual conditions that may share functional, clinical, and diagnostic features. The ICIMD aims to include any primary genetic condition in which alteration of a biochemical pathway is intrinsic to specific biochemical, clinical, and/or pathophysiological features. As new disorders are discovered, we will seek the opinion of experts in the advisory board prior to inclusion in the appropriate group of the ICIMD, thus guaranteeing the continuing relevance of this classification via regular curation and expert advice.
Circulating tumor cells (CTCs) are detectable in peripheral blood of metastatic breast cancer patients (MBC). In this paper we evaluate a new CTC separation method based on a combination of ...anti-EpCAM- and anti-cytokeratin magnetic cell separation with the aim to improve CTC detection with low target antigen densities.
Blood samples of healthy donors spiked with breast cancer cell line HCC1937 were used to determine accuracy and precision of the method. 10 healthy subjects were examined to evaluate specificity. CTC counts in 59 patients with MBC were measured to evaluate the prognostic value on overall survival.
Regression analysis of numbers of recovered vs. spiked HCC1937 cells yielded a coefficient of determination of R(2) = 0.957. The average percentage of cell recovery was 84%. The average within-run coefficient of variation for spiking of 185, 85 and 30 cells was 14%. For spiking of 10 cells the within-run CV was 30%. No CTCs were detected in blood of 10 healthy subjects examined. A standard threshold of 5 CTC/7.5 ml blood as a cut-off point between risk groups led to a highly significant prognostic marker (p < 0.001). To assess the prognostic value of medium CTC levels we additionally considered a low (CTC-L: 0 CTC), a medium (CTC-M: 1-4 CTC) and a high risk group (CTC-H: ≥5 CTC). The effect of this CTC-LMH marker on overall survival was significant as well (p < 0.001). A log-ratio test performed to compare the model with 3 vs. the model with 2 risk groups rejected the model with 2 risk groups (p = 0.026). For CTC as a count variable, we propose an offset reciprocal transformation 1/(1 + x) for overall survival prediction (p < 0.001).
We show that our CTC detection method is feasible and leads to accurate and reliable results. Our data suggest that a refined differentiation between patients with different CTC levels is reasonable.
Background
A significant number of people with bulimia nervosa (BN) or binge‐eating disorder (BED) do not seek professional help. Important reasons include limited knowledge of eating disorders ...(EDs), feelings of shame, treatment costs, and restricted access to specialized healthcare. In this study, we explored if a novel therapy delivered in a primary care setting could overcome these barriers. We investigated factors such as motivation and expectations and included the patients' and newly trained therapists' perspectives.
Method
We interviewed 10 women with BN (n = 2) or BED (n = 8), enrolled in the Physical Exercise and Dietary therapy (PED‐t) program, in a Healthy Life Center (HLC) located in a primary healthcare facility. Interview topics discussed were motivations for and expectations of therapy, and the treatment location. In addition, 10 therapists from HLC's were interviewed on their experiences with the PED‐t training program and expectations of running PED‐t within their service. The semi‐structured interviews were analyzed using reflexive thematic analysis.
Results
Most patients had limited knowledge about EDs and first realized the need for professional help after learning about PED‐t. Patients exhibited strong motivations for treatment and a positive perception of both the PED‐t, the new treatment setting, and the therapists' competencies. The therapists, following a brief training program, felt confident in their abilities to treat EDs and provide PED‐t. With minor operational adjustments, PED‐t can seamlessly be integrated into national HLC service locations.
Conclusion
PED‐t is an accessible therapeutic service that can be delivered in a primary care environment in a stepped‐care therapy model.
Public Significance
This study investigates the views and experiences of patients and newly trained therapists of PED‐t (Physical Exercise and Dietary therapy), a new program‐led primary care therapy for binge‐eating spectrum eating disorders. The treatment and the locations for the intervention, that is, local health care centers, were found to be highly acceptable to both patients and therapists, thus PED‐t could easily be integrated as a first step into a step‐care delivery model.
The cognitive interpersonal model was outlined initially in 2006 in a paper describing the valued and visible aspects of anorexia nervosa (Schmidt and Treasure, 2006). In 2013, we summarised many of ...the cognitive and emotional traits underpinning the model (Treasure and Schmidt, 2013). In this paper, we describe in more detail the perpetuating aspects of the model, which include the inter- and intrapersonal related consequences of isolation, depression, and chronic stress that accumulate in the severe and enduring stage of the illness. Since we developed the model, we have been using it to frame research and development at the Maudsley. We have developed and tested interventions for both patients and close others, refining the model through iterative cycles of model/intervention development in line with the Medical Research Council (MRC) framework for complex interventions. For example, we have defined the consequences of living with the illness on close others (including medical professionals) and characterised the intense emotional reactions and behaviours that follow. For the individual with an eating disorder, these counter-reactions can allow the eating disorder to become entrenched. In addition, the consequent chronic stress from starvation and social pain set in motion processes such as depression, neuroprogression, and neuroadaptation. Thus, anorexia nervosa develops a life of its own that is resistant to treatment. In this paper, we describe the underpinnings of the model and how this can be targeted into treatment.
Individuals with bulimia nervosa (BN) or binge-eating disorder (BED) experience more frequent and intense food cravings than individuals without binge eating. However, it is currently unclear whether ...they also show larger food cue-induced increases in craving (i.e., food cue reactivity) than those without binge eating, as suggested by conditioning theories of binge eating. A group of individuals with BN or BED (binge-eating group, n = 27) and a group of individuals with low trait food craving scores and without binge eating (control group, n = 19) reported their current food craving before and after a food cue exposure. Although food craving intensity significantly increased in both groups, this increase was significantly stronger in the binge-eating group than in the control group. This result is in line with conditioning models of binge eating that propose that food cues are conditioned stimuli that elicit a conditioned response (e.g., food craving) and that this association is stronger in individuals with binge eating. As food craving increased in individuals with low trait food craving scores as well-although to a lesser extent-previous null results might be explained by methodological considerations such as not screening control participants for trait food craving.
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