Current Anorexia Nervosa Research Articles

Examining Identity Functioning in Anorexia Nervosa Across Illness and Recovery Stages.

Research suggests that identity functioning (i.e., sense of self) issues may be a core feature of anorexia nervosa (AN). We aimed to investigate differences in identity functioning among women with AN at varying illness and recovery stages, and women with no history of eating disorders (non-ED controls). It was hypothesized that those with current AN (AN-C), weight-restored (AN-WR), and partial recovered individuals (AN-PR) would show poorer identity functioning than fully recovered individuals (AN-FR) and non-ED controls. Women (334) with AN-C (n = 74), AN-WR (n = 90), AN-PR (n = 19), AN-FR (n = 22), and non-ED controls (n = 129) completed online self-report measures of identity functioning and ED symptom severity. The AN-C group showed significantly poorer overall identity functioning, poorer consolidated identity, and significantly worse disturbed and lack of identity, than the AN-PR, AN-FR, and non-ED Control groups. The AN-WR group showed significantly poorer overall identity function, and worse lack of identity, than the AN-FR and non-ED Controls, and poorer consolidated identity and disturbed identity than non-ED Controls. Identity scores did not significantly differ between AN-PR, AN-FR, and non-ED Controls. Differences in identity functioning are identifiable among individuals at different AN recovery stages, and thus may represent an important state-based feature of AN, making it an important area of consideration in treatment.

Food Restriction in Anorexia Nervosa in the Light of Modern Learning Theory: A Narrative Review

Improvements in the clinical management of anorexia nervosa (AN) are urgently needed. To do so, the search for innovative approaches continues at laboratory and clinical levels to translate new findings into more effective treatments. In this sense, modern learning theory provides a unifying framework that connects concepts, methodologies and data from preclinical and clinical research to inspire novel interventions in the field of psychopathology in general, and of disordered eating in particular. Indeed, learning is thought to be a crucial factor in the development/regulation of normal and pathological eating behaviour. Thus, the present review not only tries to provide a comprehensive overview of modern learning research in the field of AN, but also follows a transdiagnostic perspective to offer testable explanations for the origin and maintenance of pathological food rejection. This narrative review was informed by a systematic search of research papers in the electronic databases PsycInfo, Scopus and Web of Science following PRISMA methodology. By considering the number and type of associations (Pavlovian, goal-directed or habitual) and the affective nature of conditioning processes (appetitive versus aversive), this approach can explain many features of AN, including why some patients restrict food intake to the point of life-threatening starvation and others restrict calorie intake to lose weight and binge on a regular basis. Nonetheless, it is striking how little impact modern learning theory has had on the current AN research agenda and practice.

Anorexia nervosa, weight restoration and biological siblings: Differences and similarities in clinical characteristics.

Anorexia nervosa (AN) is associated with clinical characteristics including eating disorder symptomatology, negative mood states, perfectionism and cognitive inflexibility. Whether these characteristics differ across illness stages, and are also present in first-degree relatives, demonstrating heritability, is unclear. The aim of this research was to compare current AN (c-AN), weight-restored AN (wr-AN), sisters of individuals with AN (AN-sis) and healthy controls (HC) on these measures. Eighty participants (n = 20/group) completed the study. Eating disorder symptomatology was similar among c-AN and wr-AN groups, whereas the AN-sis did not differ from either wr-AN or HC. Anxiety was significantly higher in c-AN, wr-AN and AN-sis groups, relative to HC. Increased perfectionism was identified in the c-AN and wr-AN groups compared to AN-sis and HC on the 'concern over mistakes', 'personal standards' and 'doubt and actions' subscales of the Multidimensional Perfectionism Scale. Group differences were not apparent on cognitive flexibility. These findings suggest that anxiety may be a risk factor or linked to genetic susceptibility for AN, as well as specific aspects of perfectionism that relate to self-imposed standards.

Nutrient Intake and Dietary Inflammatory Potential in Current and Recovered Anorexia Nervosa.

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN (n = 51), those recovered from AN (n = 23), and healthy controls (n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary Inflammatory Index (DII®) score and collected blood samples to measure serum concentrations of inflammatory markers. In current AN participants, we found lower intake of cholesterol, compared to HCs, and lower consumption of zinc and protein, compared to HC and recovered AN participants. A one-way ANOVA revealed no significant group differences in DII score. Multivariable regression analyses showed that DII scores were significantly associated with tumour necrosis factor (TNF)-α concentrations in our current AN sample. Our findings on nutrient intake are partially consistent with previous research. The lack of group differences in DII score, perhaps suggests that diet is not a key contributor to altered inflammatory marker concentrations in current and recovered AN. Future research would benefit from including larger samples and using multiple 24-h dietary recalls to assess dietary intake.

Eye movements in anorexia nervosa: State or trait markers?

Differences in saccadic eye movements are widely reported in mental illnesses, and can indirectly inform our understanding of neurobiological and cognitive underpinnings of psychiatric conditions, including anorexia nervosa (AN). Preliminary research has suggested that individuals with AN may show specific eye movement abnormalities; whether these deficits are representative of state or trait effects is, however, unclear. The aim of this study was to identify whether there are demonstrable differences in performance on saccadic eye movement tasks in individuals with current AN (c-AN), those who are weight-restored from AN (wr-AN), biological sisters of individuals with AN (AN-sis), and healthy controls (HC). Eighty participants took part in the study (n = 20/group). A set of saccadic eye movement tasks was administered, including prosaccade, antisaccade, memory-guided saccade, and visual scanpath tasks. The c-AN group showed an increased rate of inhibitory errors to 10° targets on the memory-guided saccade task. The results are discussed in terms of the potential role of the superior colliculus in AN, and that the findings may reflect a state measure of AN.

Exome & precision medicine in eating disorders

Introduction Eating disorders (EDs) are complex and multifactorial psychiatric illnesses associated with significant and sustained pathological disruption of food intake. The Diagnostic and Statistical Manual of Mental Illnesses (DSM-5) distinguishes anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). The neurobiological basis of food intake are well characterized. Epidemiological studies reported a heritability about 70% in AN and 60% in BN, suggesting that genetic factors are playing a significant role. AN is the most severe disorder in terms of morbidity in psychiatric illnesses, with the highest mortality rate increased by 23 fold. Treatments have a limited effectiveness, however, one third of the AN patients evolve to the remission. Goal We and collaborators from the Genetic Consortium for Anorexia Nervosa/Wellcome Trust Case Control Consortium-3 (GCAN/WTCCC3), the Anorexia Nervosa Genetics Initiative (ANGI) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED), are currently investigating molecular biology and physiology in AN patients, subjects in remission and healthy control women in the goal to identify and characterize biomarkers of diagnosis and prognosis of AN to propose precision medicine and adapted treatments. Methods Extensive clinical evaluation, genotyping of polymorphisms, exome sequencing of candidate genes or whole-exome sequencing (WES), and measure of DNA methylation levels of the whole genome or candidate genes, and blood concentration levels of candidate neuropeptides and hormones are performed in current AN patients, subjects in remission and healthy control women. Results Common genetic variants of vulnerability for AN are found by GWAS. Furthermore, rare variants or mutations are identified using the next-generation sequencing in the screening of sporadic cases or AN families. Significant differences are observed for specific DNA methylation sites and concentration levels of molecules between current AN patients compared to controls. Conclusions Convergent molecular and physiological studies suggest that the pathophysiological bases of eating disorder, and especially AN, involve both “psychiatric” and “metabolic” pathways. These omictools will allow us to enter in the precision medicine in eating disorders.

Anorexia Nervosa, Autism, and the ADOS: How Appropriate Is the New Algorithm in Identifying Cases?

Thirty years of scholarship has suggested that anorexia nervosa (AN) may be a “female presentation” of autism, supported by work which has found elevated rates of autism traits and diagnoses among women with clinical levels of AN. These traits are often assessed using the Autism Diagnostic Observation Schedule 2nd Edition (ADOS-2), considered the “gold-standard” tool. Recently, the authors of the ADOS-2 revised the diagnostic algorithm for the adult version of the assessment—the one most often used with AN patients. We therefore examined differences in the scores, rates of diagnosis, and correlations with other mental health issues between the two diagnostic algorithms among women with and without AN. One hundred seventy-five women with current AN, who had recovered from AN, and with no history of AN, between the ages of 12 and 53, took part in an ADOS-2 assessment. Their scores were then calculated according to both the original and the new algorithms. The new ADOS-2 algorithm identifies more women as potentially being on the autism spectrum than the old algorithm. Under both algorithms, more currently ill AN patients were identified as potentially being autistic than those with no history of AN. Recovered individuals represented a midpoint between the scores of those with and without AN on both algorithms. There were no correlations with mental health scores in any group, meaning that the new ADOS-2 algorithm is not falsely identifying anxious behaviors or depressive presentations as signs of autism in this group. Overall, we found that more AN patients and recovered individuals scored above cut-off on the new ADOS-2 algorithm, suggesting that women who experience AN may have more autistic traits, which in part persist following weight restoration and recovery. However, the ADOS-2 should not be used alone but in combination with broader clinical assessments to determine whether an autism diagnosis is appropriate for these women.

The Impact of Starvation on the Microbiome and Gut-Brain Interaction in Anorexia Nervosa

Interactions between the gut microbiome and the brain are of increasing interest to both researchers and clinicians. Evidence is mounting on the causal role of an altered gut microbiome in inflammatory diseases such as arthritis, inflammatory bowel disease, obesity and diabetes, and psychiatric diseases like anxiety and depression. Mechanisms include altered energy harvest from food, hormonal changes, increased gut permeability, inflammation, immune response, and a direct influence on the brain and behavior. Anorexia nervosa (AN) is the third most common disease in adolescence and exacts a high burden on patients and caregivers. It often becomes chronic and has the highest mortality of all psychiatric diseases. As AN is characterized by nutritional restrictions, weight loss, and severe behavioral symptoms including weight phobia, comorbid anxiety and depression, accompanied by endocrine alterations, increased inflammation, and immune response, exploring the role of the gut microbiome is crucial. Here, we present an overview of the potential mechanisms of interaction between the gut microbiome, the host and particularly the brain in AN and summarize the initial findings of microbiome research on AN. We conclude by identifying future research directions and potential therapeutic approaches, including nutritional interventions, probiotics, prebiotics and food supplements, that could become important additions to current AN therapy.

SA64 - FOLLOW-UP STUDY OF WHOLE-GENOME DNA METHYLATION EPIGENETIC PROFILES IN THE REMISSION OF ANOREXIA NERVOSA

Background Anorexia Nervosa (AN) is a severe psychiatric disorder with a strong heritability (about 0.6). There are no drug treatments available for AN. Interestingly, one third of patients evolved to remitters after hospitalizations and multiple adapted cares but, to date, there are no biological markers that could help to propose a prognostic to this remission. Even the genetic component to AN, there is no major gene that has been identified in AN. The mechanisms of epigenetic regulations could play a major role in the involvement in AN. We and other groups have recently performed a whole-genome DNA methylation study (methylome) in AN. We found that the differentially methylated CpG sites are located around genes involved in biological processes in link with embryonic morphogenesis, brain development and its plasticity, in particular adhesion and axon guidance. In the present study, we have screened a novel independent group of 40 AN patients. Furthermore, we have done a follow-up during more than one year, to compare the methylation profiles between the patients currently with AN and subjects that evolve to the remission. Methods Our objective is to characterize a specific methylome in AN patients that convert to remitters in the goal to identify prognostic epigenetic signatures for AN. Of the 40 AN patients, 18 evolved to the remission after one year of follow-up. The blood samples of the subjects were collected at the 2 times of the follow-up. Methylations of the DNA were measured by using the Infinium HumanMethylation450 BeadChip technology and analyzed according to the Chip Analysis Methylation Pipeline (ChAMP). Results Comparisons of AN patients to controls showed similar profiles of methylation has previously found with other patients, including the same biological processes as previously identified. We are now comparing the difference of methylation between the 18 remitters and the 18 current AN. Discussion We expect to characterize specific methylation signatures of the prognostic of the AN remission.

Associations between dimensions of anorexia nervosa and obsessive–compulsive disorder: An examination of personality and psychological factors in patients with anorexia nervosa

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders. In path analyses (N=732 women with either current AN or recovered from AN), we examined which factors were uniquely and independently associated with the core dimensions of AN and OCD. We also examined recovery from AN as a moderator. When individuals with AN reported greater concern over mistakes, they endorsed more severity in both AN and OCD core dimensions. These unique associations existed above and beyond all other transdiagnostic personality and psychological factors and regardless of AN recovery status. Concern over mistakes partially accounts for severity in the core dimensions of both AN and OCD. Concern over mistakes may represent an important target in the aetiology of AN and OCD.

Do autism spectrum disorder and anorexia nervosa have some eating disturbances in common?

A possible overlap between autism spectrum disorder (ASD) and anorexia nervosa (AN), in terms of both behavioural and cognitive features, has led to new areas of research. The aim of the present study was to examine the occurrence of eating behaviours frequently seen in ASD among adolescents and young adults with AN. The participants were females within the age range 15–25 years: 36 with current AN (32 were followed up after 1 year), 19 with ASD, and 30 healthy females. The participants completed the SWedish Eating Assessment for Autism spectrum disorders (SWEAA) and the Autism Spectrum Quotient tool (AQ). AN groups had significantly higher SWEAA scores than the healthy comparison group, also when patients had gained weight. Typical autistic eating behaviours, such as selective eating, were more common in the AN groups than in the ASD group. This is the first time that SWEAA has been implemented in an AN population. Eating behaviours frequently seen in ASD seem to be frequent in AN and some remain also after weight gain.

Executive functioning and central coherence in anorexia nervosa: Pilot investigation of a neurocognitive endophenotype.

A neurocognitive profile characterized by problems in set shifting, executive functioning, and central coherence may pre-date and maintain anorexia nervosa (AN). To test this pattern as a possible endophenotype for AN, 10 youth with current AN, 14 healthy youth, and their biological parents, participated in a neuropsychological battery. Youth with AN demonstrated significantly weaker central coherence, related to enhanced detail-focused processing. Youth with AN and their parents demonstrated significantly greater psychopathology relative to controls, and youth-parent scores were significantly correlated. The study, limited by a small sample size, found little evidence supporting a neuropsychological endophenotype for AN. Identifying a neurocognitive profile for children and adolescents with AN has important implications for the treatment of young patients.

Social attribution in anorexia nervosa.

People with anorexia nervosa (AN) report socioemotional difficulties; however, measurement has been criticised for lacking ecological validity and the state or trait nature of difficulties remains unclear. Participants (n=122) were recruited across 3 groups: people who are currently ill with AN (n=40); people who recovered (RecAN, n=18); healthy-control participants (n=64). Participants completed clinical questionnaires and the Social Attribution Task. The Social Attribution Task involves describing an animation of moving shapes, scored for number of propositions offered, accuracy, and social relevance. Groups were compared cross-sectionally. Those with current AN were assessed prepsychological and postpsychological treatments. People with AN provided fewer propositions than other groups and fewer salient social attributions than healthy-control participants. Those who recovered scored intermediately and not significantly different from either group. Following treatment, people with AN demonstrated (nonsignificant) improvements, and no significance between group differences were observed. Findings suggest difficulties for people with AN in providing spontaneous social narrative and in identifying social salience.

Cortical thickness patterns as state biomarker of anorexia nervosa.

Only few studies have investigated cortical thickness in anorexia nervosa (AN), and it is unclear whether patterns of altered cortical thickness can be identified as biomarkers for AN. Cortical thickness was measured in 19 adult women with restricting-type AN, 24 individuals recovered from restricting-type AN (REC-AN) and 24 healthy controls. Those individuals with current or recovered from AN had previously shown altered regional cortical volumes across orbitofrontal cortex and insula. A linear relevance vector machine-learning algorithm estimated patterns of regional thickness across 24 subdivisions of those regions. Region-based analysis showed higher cortical thickness in AN and REC-AN, compared to controls, in the right medial orbital (olfactory) sulcus, and greater cortical thickness for short insular gyri in REC-AN versus controls bilaterally. The machine-learning algorithm identified a pattern of relatively higher right orbital, right insular and left middle frontal cortical thickness, but lower left orbital, right middle and inferior frontal, and bilateral superior frontal cortical thickness specific to AN versus controls (74% specificity and 74% sensitivity, χ2 p < .004); predicted probabilities differed significantly between AN and controls (p < .023). No pattern significantly distinguished the REC-AN group from controls. Higher cortical thickness in medial orbitofrontal cortex and insula probably contributes to higher gray matter volume in AN in those regions. The machine-learning algorithm identified a mixed pattern of mostly higher orbital and insular, but relatively lower superior frontal cortical thickness in individuals with current AN. These novel results suggest that regional cortical thickness patterns could be state markers for AN.

Reduced Resting-State Functional Connectivity in Current and Recovered Restrictive Anorexia Nervosa.

Functional connectivity studies based on resting-state functional magnetic resonance imaging (rs-fMRI) have shown alterations in brain networks associated with self-referential processing, cognitive control, and somatosensory processing in anorexia nervosa (AN). This study aimed to further investigate the functional connectivity of resting-state networks (RSNs) in homogenous subsamples of individuals with restrictive AN (current and recovered) and the relationship this has with core eating disorder psychopathology. rs-fMRI scans were obtained from 12 female individuals with restrictive AN, 14 females recovered from restrictive AN, and 16 female healthy controls. Independent components analysis revealed a set of functionally relevant RSNs, previously reported in the literature. Dual regression analysis showed decreased temporal coherence within the lateral visual and auditory RSNs in individuals with current AN and those recovered from AN compared to healthy individuals. This decreased connectivity was also found in regions associated with somatosensory processing, and is consistent with reduced interoceptive awareness and body image perception, characteristic of AN. Widespread gray matter (GM) reductions were also found in both the AN groups, and differences in functional connectivity were no longer significant when GM maps were added as a covariate in the dual regression analysis. This raises the possibility that deficits in somatosensory and interoceptive processing observed in AN may be in part underpinned or exacerbated by GM reductions.

Heightened Olfactory Sensitivity in Young Females with Recent-Onset Anorexia Nervosa and Recovered Individuals.

IntroductionOlfaction may be related to food restriction and weight loss. However, reports regarding olfactory function in individuals with anorexia nervosa (AN) have been inconclusive.ObjectiveCharacterize olfactory sensitivity and identification in female adolescents and young adults with first-episode AN and young females recovered from AN.MethodsWe used the Sniffin’ Sticks Odor Threshold Test and Odor Identification Test to assess 43 participants with first-episode AN, 27 recovered participants, and 39 control participants. Participants completed the Importance of Olfaction questionnaire, the Beck Youth Inventory and the Eating Disorder Inventory. We also conducted a psychiatric diagnostic interview and the Autism Diagnostic Observation Schedule with participants.ResultsBoth clinical groups showed heightened olfactory sensitivity. After excluding participants with depression, participants with first-episode AN identified more odors than recovered participants.ConclusionHeightened olfactory sensitivity in AN may be independent of clinical status, whereas only individuals with current AN and without depression show more accurate odor identification.

Enhanced Early Neuronal Processing of Food Pictures in Anorexia Nervosa: A Magnetoencephalography Study.

Neuroimaging studies in Anorexia Nervosa (AN) have shown increased activation in reward and cognitive control regions in response to food, and a behavioral attentional bias (AB) towards food stimuli is reported. This study aimed to further investigate the neural processing of food using magnetoencephalography (MEG). Participants were 13 females with restricting-type AN, 14 females recovered from restricting-type AN, and 15 female healthy controls. MEG data was acquired whilst participants viewed high- and low-calorie food pictures. Attention was assessed with a reaction time task and eye tracking. Time-series analysis suggested increased neural activity in response to both calorie conditions in the AN groups, consistent with an early AB. Increased activity was observed at 150 ms in the current AN group. Neuronal activity at this latency was at normal level in the recovered group; however, this group exhibited enhanced activity at 320 ms after stimulus. Consistent with previous studies, analysis in source space and behavioral data suggested enhanced attention and cognitive control processes in response to food stimuli in AN. This may enable avoidance of salient food stimuli and maintenance of dietary restraint in AN. A later latency of increased activity in the recovered group may reflect a reversal of this avoidance, with source space and behavioral data indicating increased visual and cognitive processing of food stimuli.

Exploring neurocognitive inefficiencies in anorexia nervosa

Neurocognitive findings in the field of eating disorders have consistently highlighted two aspects of executive functioning that pose particular difficulties for those with anorexia nervosa (AN): poor set-shifting and weak coherence. The current piece of research aims to explore the prevalence and clinical correlates of women with AN that show a neurocognitive profile consistent with both poor set-shifting and weak coherence. Fifty-four outpatient women with AN were administered a semi-structured clinical interview and six neurocognitive tasks assessing neurocognitive profile, together with self-report measures. One in five women with current AN met criteria for both poor set-shifting and detail-focussed neurocognitive inefficiencies. Compared to those with one, those with both inefficiencies showed a more severe clinical picture and poorer prognostic factors. Identification of the subgroup of those with AN that present with both neurocognitive inefficiencies simultaneously may flag cases of higher clinical risk where a more targeted intervention may be required. Clinical implications will be discussed, together with an update on intervention research based on neurocognitive profile (cognitive remediation therapy).

Emotional facial expression in women recovered from anorexia nervosa.

BackgroundRecent models of anorexia nervosa (AN) have emphasised the importance of social and emotional difficulties as maintenance factors of the disorder, however, empirical data are limited. The aim of this study was to examine whether altered emotional facial expression, previously observed in people currently ill with anorexia nervosa, is limited to the ill state or present in people recovered from the illness.MethodsThe sample consisted of 123 participants [49 AN, 21 recovered AN (RecAN) and 53 healthy controls (HC)]. Participants watched three films clips (amusing, neutral, sad) whilst their facial expressions were recorded and completed the positive and negative affect scale (PANAS) to record subjective experience. Facial expressions were subsequently coded for frequency of positive and negative expression and frequency of looking away.ResultsIn response to the amusing clip, AN participants showed significantly less positive expression than both HC and RecAN groups and both AN and RecAN showed more negative expression than HC with no difference between groups in looking away.In response to the sad clip there was no difference between groups in positive expression, but current AN participants showed significantly less negative expression than HC and looked away from the stimuli more than RecAN or HC.In terms of their subjective emotional experience, patients with current AN reported less positive emotion in response to both the amusing and the sad film clip. There was no difference between groups in subjective negative experience.ConclusionsAlterations in facial expression are present in people currently ill with AN contributing to the social difficulties found in AN and potentially exacerbating resistance to treatment. Some alterations in facial expression are found in women with a past history of AN but not to the same extent as those shown in the currently ill group. Future studies need to use a wider range of stimuli involving different emotions to corroborate findings.

Liking compared with wanting for high- and low-calorie foods in anorexia nervosa: aberrant food reward even after weight restoration

Recent frameworks for understanding food rewards recognize the role of separable affective and motivational processes (liking and wanting) in driving human eating behavior. Separate assessments of liking and wanting may aid in understanding the complex eating-related behaviors seen in anorexia nervosa (AN). The aim of this study was to examine separately liking and wanting for foods of different energy densities in women at different stages of AN and in healthy volunteers at both an implicit and an explicit level. Explicit liking and wanting responses to high- and low-calorie foods were derived from analog ratings, whereas an implicit "wanting" measure was identified by using reaction time in a forced-choice procedure. Explicit and implicit processes were compared across 3 groups of AN participants (current AN, weight-restored AN, and recovered AN) and healthy volunteers. Currently underweight AN participants explicitly wanted high-calorie foods less than did the other groups. Both current and weight-restored AN groups demonstrated significantly less implicit "wanting" for high-calorie foods and more implicit "wanting" for low-calorie foods-an inverted pattern to never-ill participants. The aberrant responses to food that characterize AN may be driven more by altered motivational salience ("wanting") than by explicit liking responses. This pattern of aberrant food reward appears to be independent of weight status. Examining the processes that motivate approach or avoidance of low- and high-calorie foods in AN may aid the development of targeted strategies to augment existing interventions.