Bethan Dalton

A systematic review of the relationship between eating, weight and inhibitory control using the stop signal task.

Altered inhibitory control (response inhibition, reward-based inhibition, cognitive inhibition, reversal learning) has been implicated in eating disorders (EDs) and obesity. It is unclear, however, how different types of inhibitory control contribute to eating and weight-control behaviours. This review evaluates the relationship between one aspect of inhibitory control (a reactive component of motor response inhibition measured by the stop signal task) and eating/weight in clinical and non-clinical populations. Sixty-two studies from 58 journal articles were included. Restrained eaters had diminished reactive inhibitory control compared to unrestrained eaters, and showed greatest benefit to their eating behaviour from manipulations of inhibitory control. Obese individuals may show less reactive inhibitory control but only in the context of food-specific inhibition or after executive resources are depleted. Of the limited studies in EDs, the majority found no impairment in reactive inhibitory control, although findings are inconsistent. Thus, altered reactive inhibitory control is related to some maladaptive eating behaviours, and hence may provide a therapeutic target for behavioural manipulations and/or neuromodulation. However, other types of inhibitory control may also contribute. Methodological and theoretical considerations are discussed.

A systematic review of temporal discounting in eating disorders and obesity: Behavioural and neuroimaging findings.

OBJECTIVE Eating Disorders (ED) and obesity are suggested to involve a spectrum of self-regulatory control difficulties. Temporal discounting (TD) tasks have been used to explore this idea. This systematic review examines behavioural and neuroimaging TD data in ED and obesity. METHOD Using PRISMA guidelines, we reviewed relevant articles in MEDLINE, PsycINFO and Embase from inception until 17th August 2016. Studies that reported behavioural differences in TD and/or TD neuroimaging data in ED/obesity were included. RESULTS Thirty-one studies were included. Limited data suggest that BN, BED and obesity are associated with increased TD, whilst data in AN are mixed. Aberrant neural activity in frontostriatal circuitry is implicated. TD tasks vary widely and TD in ED/obesity may vary according to factors such as illness stage. CONCLUSION Our findings suggest altered self-regulatory control in ED and obesity. TD tasks are heterogeneous, limiting generalisability of findings. Research into whether TD is multidimensional, along with transdiagnostic neuroimaging research is needed. Assessment of TD may be useful in psychoeducation, outcome prediction and treatment of ED/obesity.

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial

Background Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. Objective This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Methods Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. Results AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. Conclusions These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN.

What side effects are problematic for patients prescribed antipsychotic medication?: The Maudsley Side Effects (MSE) measure for antipsychotic medication

Background Capturing service users’ perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. Method An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. Results MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted ‘putting on weight’ which was more distressing, more severe and had more life impact in those for whom it was most important. Conclusions MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

Neuromodulation and neurofeedback treatments in eating disorders and obesity

Purpose of review Psychological interventions are the treatment of choice for most eating disorders; however, significant proportions of patients do not recover with these. Advances in understanding of the neurobiology of eating disorders have led to the development of targeted treatments, such as deep brain stimulation (DBS), noninvasive brain stimulation (NIBS), and neurofeedback. We review the emerging clinical evidence for the use of these interventions in eating disorders and obesity, together with their theoretical rationale. Finally, we reflect on future developments. Recent findings During the last 20 months, seven case studies/series and seven randomized controlled trials (RCTs) of NIBS or neurofeedback in different eating disorders, obesity, or food craving have appeared. These have largely had promising results. One NIBS trial, using a multisession protocol, was negative. A case series of subcallosal DBS in anorexia nervosa has also shown promise. A search of trial registries identified a further 21 neuromodulation/feedback studies in progress, indicating that neuromodulation/feedback is an area of growing interest. Summary At present, neuromodulation and neurofeedback are largely experimental interventions; however, growing understanding of the mechanisms involved, together with the rising number of studies in this area, means that the clinical utility of these interventions is likely to become clearer soon.

A Meta-Analysis of Cytokine Concentrations in Eating Disorders

Cytokines are signalling molecules, which play an important role in both immune system function and brain development and function, and subsequently mental states and behaviour. Cytokines have been implicated in eating disorders (EDs) due to their role in psychological health, body weight and appetite regulation. This meta-analysis examined cross-sectional and longitudinal studies measuring concentrations of cytokines in individuals with EDs. Using PRISMA guidelines, we systematically reviewed relevant articles in PubMed, Web of Science, and MEDLINE. Random-effects meta-analyses were conducted for interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α, independently, firstly with all EDs combined and then stratified by ED diagnosis. Twenty-five studies were included: serum/plasma cytokine concentrations were measured in people with anorexia nervosa (AN) in 23 studies and bulimia nervosa (BN) in 4 studies. TNF-α and IL-6 were elevated in ED participants compared to healthy controls (HCs). Specifically, this pattern was seen only when comparing AN participants to HCs. Concentrations of these cytokines did not differ between people with BN and HCs. IL-1β and TGF-β did not differ between HCs and any ED group. Therefore, AN seems to be associated with elevated concentrations of TNF-α and IL-6. Considering the role of cytokines in appetite, mood regulation, and anxiety, these pro-inflammatory cytokines could be a potential future drug target to help people with AN, not only with weight gain, but also with various coexisting psychological problems. Future studies should consider confounding factors that affect cytokine concentrations and report ED-relevant clinical characteristics.

A SYSTEMATIC REVIEW OF TUMOR NECROSIS FACTOR-α IN POST-TRAUMATIC STRESS DISORDER: EVIDENCE FROM HUMAN AND ANIMAL STUDIES

BACKGROUND Growing evidence suggests a pathophysiological role of cytokines in post-traumatic stress disorder (PTSD). Tumor necrosis factor (TNF)-α is a key cytokine. Therefore, we performed a systematic review to examine the findings regarding TNF-α derived from both animal and human studies of PTSD. METHODS Using PRISMA guidelines, we reviewed relevant articles in PubMed from inception until 11th April 2017. Human studies that reported group comparisons and/or longitudinal investigations of TNF-α production/concentration were included. Research reporting on TNF-α levels in animal models of PTSD were also included. RESULTS Twenty-seven articles were identified. Data from human cross-sectional studies suggests that plasma/serum levels of TNF-α are elevated in those with PTSD, as compared to healthy controls. Longitudinal assessments of TNF-α are limited and data are mixed. Limited data from animal studies suggest an increased TNF-α production in the hippocampus of rats following stress, which can be reversed by immunomodulatory drugs. CONCLUSIONS Our findings suggest TNF-α may be a potential biomarker and treatment target for PTSD. Findings need to be considered in light of heterogeneous methods for measurement and analysis of TNF-α concentration. Longitudinal research is needed to understand the role of TNF-α in the development and/or maintenance of PTSD.

Inflammatory Markers in Anorexia Nervosa: An Exploratory Study

Inflammation has been suggested to play a pathophysiological role in anorexia nervosa (AN). In this exploratory cross-sectional study, we measured serum concentrations of 40 inflammatory markers (including cytokines, chemokines, and adhesion molecules) and brain-derived neurotrophic factor (BDNF) in people with AN (n = 27) and healthy controls (HCs) (n = 13). Many of these inflammatory markers had not been previously quantified in people with AN. Eating disorder (ED) and general psychopathology symptoms were assessed. Body mass index (BMI) and body composition data were obtained. Interleukin (IL)-6, IL-15, and vascular cell adhesion molecule (VCAM)-1 concentrations were significantly elevated and concentrations of BDNF, tumor necrosis factor (TNF)-β, and vascular endothelial growth factor (VEGF)-A were significantly lower in AN participants compared to HCs. Age, BMI, and percentage body fat mass were identified as potential confounding variables for several of these inflammatory markers. Of particular interest is that most of the quantified markers were unchanged in people with AN, despite them being severely underweight with evident body fat loss, and having clinically significant ED symptoms and severe depression and anxiety symptoms. Future research should examine the replicability of our findings and consider the effect of additional potential confounding variables, such as smoking and physical activity, on the relationship between AN and inflammation.

A systematic review of in vitro cytokine production in eating disorders

BACKGROUND Eating disorders (EDs) have been associated with alterations in cytokine concentrations and production. This review examines whether in vitro cytokine production (i) is altered in people with EDs compared to healthy participants; and (ii) changes in response to treatment? METHODS Using PRISMA guidelines, we systematically reviewed articles reporting group comparisons or longitudinal assessments of spontaneous and/or stimulated cytokine production in vitro in people with EDs. RESULTS Twelve studies were included. Cross-sectional results were mixed in anorexia nervosa. Only one study measured cytokine production in bulimia nervosa. Two longitudinal studies showed that daily yoghurt consumption increases phytohemagglutinin-stimulated interferon-γ production in anorexia nervosa. CONCLUSION The mixed results could be accounted for by variations in experimental design. Our findings suggest that cytokine production could possibly be modulated through dietary interventions. However, due to the methodological heterogeneity and shortcomings of the included studies, it seems unreasonable to draw further conclusions.

A Systematic Review of Interleukin-1β in Post-Traumatic Stress Disorder: Evidence from Human and Animal Studies

Pro-inflammatory cytokines, such as interleukin (IL)-1β, have been implicated as underlying pathophysiological mechanisms and potential biomarkers of post-traumatic stress disorder (PTSD). This systematic review examines data regarding IL-1β production/concentration in human and animal studies of PTSD. In accordance with PRISMA guidelines, relevant articles from PubMed were reviewed from inception until July 10, 2017. Nineteen studies were eligible for inclusion. Animal studies demonstrated increased hippocampal IL-1β in rodent models of PTSD. Several immunomodulatory drugs were shown to reduce elevated IL-1β levels and anxiety-like behaviors in animals. Human cross-sectional studies showed contradictory results; serum and plasma IL-1β concentrations in PTSD patients were either elevated or did not differ from control groups. In vitro IL-1β production by stimulated cells demonstrated no difference between PTSD and control participants, although spontaneous in vitro production of IL-1β was increased in the PTSD group. The findings from 2 longitudinal studies were inconsistent. Given the conflicting findings, it is premature to consider IL-1β as a biomarker of PTSD. Anti-inflammatory agents may reduce IL-1β, and be a potential basis for future therapeutic agents in PTSD treatment. More longitudinal research is needed to better understand the role of IL-1β in the development and/or maintenance of PTSD.