Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.

OBJECTIVE: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. METHODS: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. RESULTS: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. DISCUSSION: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. PUBLIC SIGNIFICANCE: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.

The role of psychosocial well-being and emotion-driven impulsiveness in food choices of European adolescents.

BACKGROUND: It is unclear whether a hypothetical intervention targeting either psychosocial well-being or emotion-driven impulsiveness is more effective in reducing unhealthy food choices. Therefore, we aimed to compare the (separate) causal effects of psychosocial well-being and emotion-driven impulsiveness on European adolescents' sweet and fat propensity. METHODS: We included 2,065 participants of the IDEFICS/I.Family cohort (mean age: 13.4) providing self-reported data on sweet propensity (score range: 0 to 68.4), fat propensity (range: 0 to 72.6), emotion-driven impulsiveness using the UPPS-P negative urgency subscale, and psychosocial well-being using the KINDLR Questionnaire. We estimated, separately, the average causal effects of psychosocial well-being and emotion-driven impulsiveness on sweet and fat propensity applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). Further, we investigated a potential indirect effect of psychosocial well-being on sweet and fat propensity mediated via emotion-driven impulsiveness using a causal mediation analysis. RESULTS: If all adolescents, hypothetically, had high levels of psychosocial well-being, compared to low levels, we estimated a decrease in average sweet propensity by 1.43 [95%-confidence interval: 0.25 to 2.61]. A smaller effect was estimated for fat propensity. Similarly, if all adolescents had high levels of emotion-driven impulsiveness, compared to low levels, average sweet propensity would be decreased by 2.07 [0.87 to 3.26] and average fat propensity by 1.85 [0.81 to 2.88]. The indirect effect of psychosocial well-being via emotion-driven impulsiveness was 0.61 [0.24 to 1.09] for average sweet propensity and 0.55 [0.13 to 0.86] for average fat propensity. CONCLUSIONS: An intervention targeting emotion-driven impulsiveness, compared to psychosocial well-being, would be marginally more effective in reducing sweet and fat propensity in adolescents.

Exploring the intersection of autism spectrum disorder and eating disorders: understanding the unique challenges and treatment considerations for autistic women with eating disorders.

PURPOSE OF REVIEW: Autistic women struggle with high levels of both autistic eating behaviours and disordered eating behaviours , which might make them particularly vulnerable to develop eating disorders. Research investigating the presence and characteristics of eating disorders in autistic women is however limited, as is research examining the role of autism in the treatment and recovery of an eating disorder in autistic women. RECENT FINDINGS: The link between autism and eating disorders has mainly been investigated from the field of eating disorder research, with studies finding an overrepresentation of autism or autistic traits in eating disorders populations. Findings also suggest that autism or autistic traits are associated with a more serious presentation of the eating disorders, including a higher chance of a chronic course of the eating disorders. Most studies however lack comprehensive autism assessments, making it difficult to determine the actual prevalence of autism and its role in women with eating disorders. SUMMARY: Autistic women with an eating disorder seem to suffer from more complex eating disorders and seem to not benefit from current treatment modalities. This could be partly related to specific autism characteristics such as sensory sensitivities, which are not being considered by current treatment protocols. Future research needs to shed light on what underlies the eating behaviours of autistic women with an eating disorder, in order to help to adapt current treatment modalities to meet the unique needs of these women.

Common Genetic Variation and Age of Onset of Anorexia Nervosa.

Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h 2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.

Design and testing of a health economic Markov model for treatment of anorexia nervosa.

OBJECTIVES: Anorexia Nervosa (AN) is a severe psychiatric disorder and knowledge about the cost-effectiveness of potential interventions is limited. The aim of this paper is to introduce the Trimbos Institute health economic cost-effectiveness model for Anorexia Nervosa (AnoMod-TI), a flexible modeling tool for assessing the long-term cost-effectiveness of interventions for AN in late adolescent and adult patients, which could support clinical decision making. METHODS: AnoMod-TI is a state-transition cohort simulation (Markov) model developed from a Dutch societal perspective, which consists of four health states - namely full remission (FR), partial remission (PR), AN and death. Results are expressed as total healthcare costs, QALYs and incremental cost-effectiveness ratio. RESULTS: For the purpose of demonstrating AnoMod-TI and how it could be used to estimate cost-effectiveness over a 20-year time horizon, it was applied to a hypothetical treatment scenario. Results illustrate how a relatively costly intervention with only modest effects can still be cost-effective in the long term. CONCLUSIONS: AnoMod-TI can be used to examine long-term cost-effectiveness of various interventions aimed at either treating AN or preventing relapse from a state of partial or full remission. AnoMod-TI is freely available upon request to the authors.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN. METHODS: This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology. DISCUSSION: Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017130 . Registered on 12 November 2019.

Problematic eating behaviours of autistic women-A scoping review.

AIM: Eating and feeding behaviours of autistic individuals and related consequences have been mainly investigated in autistic children or in autistic adults with intellectual disabilities. Behaviours such as food selectivity or food neophobia have been shown to persist into adolescence and adulthood and are associated with aversive consequences. However, much less is known about the eating behaviours of autistic adults without intellectual disabilities, especially those of women. By means of a scoping review, we aim to assess the extent of the scientific literature on what is known about the eating behaviours of these women and the possible consequences of such eating behaviour. METHOD: Medline, Cochrane, PubMed and PsycInfo databases were searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Five studies met the eligibility criteria and were included in this review. Autistic women not only reported high levels of eating behaviour frequently seen in autism spectrum disorders (ASD), but also high levels of disordered eating behaviour, similar to that of women with eating disorders. CONCLUSIONS: Autistic women seem to exhibit high levels of eating behaviour frequently seen in ASD as well as disordered eating behaviour. Future research needs to shed light on what underlies these problematic eating behaviours, in order to help to adapt current treatment modalities to meet the unique needs of these women.

Associations Between Psychosocial Well-Being, Stressful Life Events and Emotion-Driven Impulsiveness in European Adolescents.

Knowing the extent to which mental well-being and stressful life events during adolescence contribute to personality characteristics related to risk-taking behaviors, such as emotion-driven impulsiveness, is highly relevant for the development of health promotion measures. This study examined whether psychosocial well-being and different stressful life events are associated with emotion-driven impulsiveness. In total, 3,031 adolescents (52% girls; Mage = 13.6 years) were included from the I. Family Study, a cross-sectional examination on lifestyle-related behaviors conducted across eight European countries in 2013/14. Linear mixed-effects regression models showed that higher psychosocial well-being was associated with lower emotion-driven impulsiveness independent of socio-demographic, health-related, and parental variables. A higher number of stressful life events was associated with higher emotion-driven impulsiveness. Psychosocial well-being and stressful life events need to be further considered in the development and tailoring of health promotion strategies that aim to reduce emotion-driven impulsiveness.

How deep is your thought? The relations between intolerance of uncertainty, worry and weight and shape concerns in adolescent girls with anorexia nervosa.

BACKGROUND: Inherent to anorexia nervosa are repetitive thoughts about weight and shape. Growing research suggests the relevance of intolerance of uncertainty and worry in maintaining these types of repetitive thoughts. The relation between these cognitive processes and weight and shape concerns in adolescent girls with anorexia nervosa is understudied. This study investigated associations between prospective (desire for predictability) and inhibitory (uncertainty paralysis) intolerance of uncertainty, and weight and shape concerns and the mediating role of worry in these associations. METHODS: In a cross-sectional study, 93 adolescent girls with anorexia nervosa completed questionnaires measuring the variables of interest. A mediation model with worry as a mediator between inhibitory and prospective intolerance of uncertainty and weight and shape concerns was tested. RESULTS: A total and direct effect of inhibitory intolerance of uncertainty on weight and shape concerns was found. Worry did not mediate this relation. CONCLUSIONS: These results confirm the importance of inhibitory intolerance of uncertainty in adolescent girls with anorexia nervosa, more specifically to weight and shape concerns. This group may benefit from intervention strategies targeting intolerance of uncertainty. General worry seems less relevant to weight and shape concerns in adolescent girls with anorexia nervosa. Adolescent girls with anorexia nervosa often experience repetitive thoughts about weight and shape. Growing research suggests the relevance of intolerance of uncertainty and worry in maintaining these types of repetitive thoughts. Intolerance of uncertainty is defined as the incapacity to tolerate uncertainty and is often divided into two components; prospective intolerance of uncertainty (desire for predictability) and inhibitory intolerance of uncertainty (uncertainty paralysis). The relation between intolerance of uncertainty, worry and weight and shape concerns in adolescent girls with anorexia nervosa is understudied. This study aims to investigate study relations between prospective and inhibitory intolerance of uncertainty, worry, and weight and shape concerns. A total of 93 adolescent girls with anorexia nervosa completed three questionnaires, measuring prospective and inhibitory intolerance of uncertainty worry, and weight and shape concerns, respectively. The results of this study confirmed the importance of inhibitory intolerance of uncertainty in adolescent girls with anorexia nervosa, more specifically to weight and shape concerns. This group may benefit from intervention strategies targeting intolerance of uncertainty. General worry seems less relevant to weight and shape concerns in adolescent girls.

Understanding implicit and explicit learning in adolescents with and without anorexia nervosa.

BACKGROUND: Cognitive disturbances such as impairments in learning are thought to play a role in adult Anorexia Nervosa (AN). It is remains unclear to what extent these disturbances result from starvation of the brain, or relate to an abnormal premorbid cognitive profile. This study investigates learning processes in adolescents with AN, hypothesizing that implicit learning is intact, as found previously in explicit learning tasks. Secondly, we hypothesized that anxiety and depression symptoms, inherent to AN, are associated to learning processes in AN. METHODS: In total 46 adolescents diagnosed with AN and 44 control participants were administered an implicit category learning task in which they were asked to categorize simple perceptual stimuli (Gabor patches) based on a linear integration (i.e., an implicit task) of orientation and spatial frequency of the stimulus. A subgroup of adolescents (n = 38) also completed a task assessing explicit learning. RESULTS: Model-based analyses indicated that adolescents with AN performed significantly more accurately compared to their healthy peers regardless of whether they used the optimal strategy or not. Depression and anxiety did not relate to learning performance in the AN group. CONCLUSIONS: Overall, our findings of augmented implicit and explicit learning in adolescents with AN corroborate recent studies that suggested higher stimulus-response learning during prediction error paradigms. Learning disturbances in adult AN may then be at least partly due to long-term malnourishment, highlighting the importance of early recognition and refeeding in treatments for AN.

We know that some adults with anorexia nervosa (AN) experience difficulties in learning processes. It is remains unclear to what extent these difficulties result from long-term starvation of the brain. This study looked at learning processes in adolescents with AN who have a relatively short duration of illness. We also investigated whether anxiety and depression affected learning. Forty-six adolescents diagnosed with AN and 44 control participants completed tasks that assessed learning and questionnaires assessing depression and anxiety. We found that adolescents with AN performed more accurately compared to their healthy peers. However, depression and anxiety did not relate to learning performance. Overall, our findings suggest that individuals with AN, relative to their healthy peers, may be quicker in forming automatic responses and behaviors to cues. Learning disturbances in adult AN may then be at least partly due to long-term malnourishment, which highlights the importance of early recognition of AN and refeeding in treatments for AN.

Relationships between educational achievement, intelligence, and perfectionism in adolescents with eating disorders.

OBJECTIVE: High performance at school is associated with the risk of eating disorders (EDs), and perfectionism is proposed as an explanatory factor for this association. This study aims to evaluate (a) potential discrepancies between the measured IQ of adolescents with EDs and the IQ that is expected given their educational track, and (b) to what extent perfectionism was associated with educational achievement independent from IQ. METHOD: WISC-III Verbal IQ, Performance IQ, and Full Scale IQ of 386 adolescent ED patients were compared with population norms for their educational track, using one-sample t tests. The association between self-oriented perfectionism (Eating Disorder Inventory-2) and educational achievement, adjusted for IQ, was determined with sequential ordinal regression analyses. RESULTS: Over 50% of the patients received pre-university education, the most complex educational track. For patients receiving education in the second most complex track, IQ-scores were lower than normative data for that track. For patients receiving pre-university education, the verbal IQ was lower than the norm for that track. Self-oriented perfectionism was associated with educational achievement independent from intelligence. DISCUSSION: This study suggests that high educational achievement is common in adolescents with EDs. Particularly for patients who receive education in the most complex tracks the demands at school may be higher than they can handle, based on their IQ. Self-oriented perfectionism contributed to educational achievement independent from IQ. Our results indicate that treatment for EDs should include awareness for the possibility of a too high target level of patients at school and perfectionism.

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

Effectiveness of the Boston University Approach to Psychiatric Rehabilitation in Improving Social Participation in People With Severe Mental Illnesses: A Randomized Controlled Trial.

BACKGROUND: People with severe mental illnesses (SMIs) have difficulty participating in society through work or other daily activities. AIMS: To establish the effectiveness with which the Boston University Approach to Psychiatric Rehabilitation (BPR) improves the level of social participation in people with SMIs, in the Netherlands. METHOD: In a randomized controlled trial involving 188 people with SMIs, we compared BPR (n = 98) with an Active Control Condition (ACC, n = 90) (Trial registration ISRCTN88987322). Multilevel modeling was used to study intervention effects over two six-month periods. The primary outcome measure was level of social participation, expressed as having participated in paid or unpaid employment over the past six months, as the total hours spent in paid or unpaid employment, and as the current level of social participation. Secondary outcome measures were clients' views on rehabilitation goal attainment, Quality of Life (QOL), personal recovery, self-efficacy, and psychosocial functioning. RESULTS: During the study, social participation, QOL, and psychosocial functioning improved in patients in both groups. However, BPR was not more effective than ACC on any of the outcomes. Better social participation was predicted by previous work experience and a lower intensity of psychiatric symptoms. CONCLUSIONS: While ACC was as effective as BPR in improving the social participation of individuals with SMIs, much higher percentages of participants in our sample found (paid) work or other meaningful activities than in observational studies without specific support for social participation. This suggests that focused rehabilitation efforts are beneficial, irrespective of the specific methodology used.

Developments in the psychological treatment of anorexia nervosa and their implications for daily practice.

PURPOSE OF REVIEW: Our aim is to give an overview of the recent literature on psychological treatment for young adults and adults with anorexia nervosa and to discuss the implications of the findings for clinical practice. RECENT FINDINGS: Three systematic reviews and meta-analyses have recently been published on psychological treatments for anorexia nervosa. Treatment outcomes are still modest and mainly focus on weight outcome, although outcomes for eating disorder disease and quality of life have also been reported. Adhering to a treatment protocol might lead to faster and better results. SUMMARY: For children and adolescents with anorexia nervosa, the major guidelines recommend a family-based treatment. The treatments of choice for young adults and adults with anorexia nervosa are the Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), Cognitive Behaviour Therapy-Enhanced (CBT-E) and Specialist Supportive Clinical Management (SSCM), but none of these treatments seem to be superior. In search of other ways to improve outcome, shared decision making may be a way to help patients become more involved in their treatment, enhance their motivation and consequently improve the outcome.

Effectiveness of enhanced cognitive behavior therapy for eating disorders: A randomized controlled trial.

OBJECTIVE: Enhanced cognitive behavior therapy (CBT-E) is a transdiagnostic treatment suitable for the full range of eating disorders (EDs). Although the effectiveness of CBT(-E) is clear, it is not being used as widely in clinical practice as guidelines recommend. The aim of the present study was to compare the effectiveness of CBT-E with treatment as usual (TAU), which was largely based on CBT principles. METHOD: We conducted a randomized controlled trial on a total of 143 adult patients with an ED who received either CBT-E or TAU. The primary outcome was recovery from the ED. Secondary outcome measures were levels of ED psychopathology, anxiety, and depressive symptoms. Self-esteem, perfectionism, and interpersonal problems were repeatedly measured to examine possible moderating effects. We explored differences in duration and intensity between conditions. RESULTS: After 80 weeks, there were no differences between conditions in decrease in ED psychopathology, or symptoms of anxiety and depression. However, in the first six weeks of treatment there was a larger decrease in ED psychopathology in the CBT-E condition. Moreover, when the internationally most widely used definition of recovery was applied, the recovery rate at 20 weeks of CBT-E was significantly higher (57.7%) than of TAU (36.0%). At 80 weeks, this difference was no longer significant (CBT-E 60.9%; TAU 43.6%). Furthermore, CBT-E was more effective in improving self-esteem and was also the less intensive and shorter treatment. DISCUSSION: With broader use of CBT-E, the efficiency, accessibility and effectivity (on self-esteem) of treatment for EDs could be improved.

Cognitive Remediation Therapy Does Not Enhance Treatment Effect in Obsessive-Compulsive Disorder and Anorexia Nervosa: A Randomized Controlled Trial.

BACKGROUND: Guideline-recommended therapies are moderately successful in the treatment of obsessive-compulsive disorder (OCD) and anorexia nervosa (AN), leaving room for improvement. Cognitive inflexibility, a common trait in both disorders, is likely to prevent patients from engaging in treatment and from fully benefiting from existing therapies. Cognitive remediation therapy (CRT) is a practical augmentation intervention aimed at ameliorating this impairing cognitive style prior to disorder-specific therapy. OBJECTIVE: To compare the effectiveness of CRT and a control treatment that was not aimed at enhancing flexibility, named specialized attention therapy (SAT), as add-ons to treatment as usual (TAU). METHODS: In a randomized controlled multicenter clinical trial, 71 adult patients with OCD and 61 with AN were randomized to ten twice-weekly sessions with either CRT or SAT, followed by TAU. Patients were evaluated at baseline, post-CRT/SAT, and after 6 and 12 months, with outcomes being quantified using the Yale-Brown Obsessive Compulsive Scale for OCD and the Eating Disorder Examination Questionnaire for AN. RESULTS: Across study groups, most importantly CRT+TAU was not superior to control treatment (SAT)+TAU in reducing OCD and AN pathology. Contrary to expectations, SAT+TAU may have been more effective than CRT+TAU in patients being treated for OCD. CONCLUSIONS: CRT did not enhance the effect of TAU for OCD and AN more than SAT. Unexpectedly, SAT, the control condition, may have had an augmentation effect on TAU in OCD patients. Although this latter finding may have been due to chance, the effect of SAT delivered as a pretreatment add-on intervention for adults with OCD and AN merits future efforts at replication.

Insensitivity to Losses: A Core Feature in Patients With Anorexia Nervosa?

BACKGROUND: Patients with anorexia nervosa (AN) demonstrate aberrations in choice behavior, including impairments in laboratory measures of decision making. Although a wealth of studies suggest that these aberrations arise from alterations in value processing, it remains unclear by which core component of value processing this is mediated. METHODS: We fit trial-by-trial data of patients with AN (n = 60 first cohort, n = 216 second cohort) and healthy control participants (n = 55) performing the Iowa Gambling Task to a computational model based on prospect utility theory. We determined, per participant, the best-fit model parameters and compared these between the groups. RESULTS: Analyses revealed a decreased estimate of model parameter λ in patients with AN, indicative of an attenuation of loss-aversive behavior in the Iowa Gambling Task. In comparison, measures of reward sensitivity, value-based learning, and exploration versus exploitation were unaltered in patients with AN. A measurement in a second independent cohort replicated the finding that loss aversion, typically observed in healthy individuals, is reduced in patients with AN. CONCLUSIONS: We show that patients with AN, in contrast to healthy control participants, demonstrate reduced loss-aversive behavior. This finding provides important fundamental insights into the decision-making capacity of patients with AN, suggesting alterations in the mechanisms involved in value processing related to negative feedback.

Emotion-driven impulsiveness but not decision-making ability and cognitive inflexibility predicts weight status in adults.

In this study we aimed to determine whether decision-making ability, cognitive inflexibility and emotion-driven impulsiveness are associated with weight status as expressed by body mass index (BMI), percentage body fat, waist circumference and skinfold thickness in adults from eight different European countries taking part in the I.Family study. The Bechara Gambling Task was used to assess decision-making ability (n = 1717). The Berg Card Sorting Test was used to measure cognitive inflexibility (n = 1509). Lastly, the negative urgency subscale from the UPPS-P Impulsive Behavior Scale was used to measure emotion-driven impulsiveness (n = 4450). Hierarchical regression analyses showed that more emotion-driven impulsiveness was statistically significantly associated with a higher BMI, a higher percentage body fat, and a larger waist circumference in adults, controlling for age, sex, socioeconomic status, country and binge eating; but not with skinfold thickness. Cognitive inflexibility and decision-making ability were not statistically significantly associated with any of the weight status related variables. These results support that impulsivity in response to negative emotions, but not decision-making ability or cognitive inflexibility, is associated with the susceptibility to excessive weight (as indicated by a higher BMI, a higher percentage body fat, and a larger waist circumference). In people behaving impulsively when emotional, focusing on reducing negative affect or improving coping skills is of interest in interventions targeting obesity. CLINICAL TRIAL REGISTRATION: The I.Family study is registered in the ISRCTN registry (ISRCTN62310987) on February 23, 2018.

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.