Reduced dorsal fronto-striatal connectivity at rest in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear. METHODS: The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality. RESULTS: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality. CONCLUSIONS: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

Autonomic indices and loss-of-control eating in adolescents: an ecological momentary assessment study.

BACKGROUND: Loss-of-control (LOC) eating commonly develops during adolescence, and it predicts full-syndrome eating disorders and excess weight gain. Although negative emotions and emotion dysregulation are hypothesized to precede and predict LOC eating, they are rarely examined outside the self-report domain. Autonomic indices, including heart rate (HR) and heart rate variability (HRV), may provide information about stress and capacity for emotion regulation in response to stress. METHODS: We studied whether autonomic indices predict LOC eating in real-time in adolescents with LOC eating and body mass index (BMI) ⩾70th percentile. Twenty-four adolescents aged 12-18 (67% female; BMI percentile mean ± standard deviation = 92.6 ± 9.4) who reported at least twice-monthly LOC episodes wore biosensors to monitor HR, HRV, and physical activity for 1 week. They reported their degree of LOC after all eating episodes on a visual analog scale (0-100) using a smartphone. RESULTS: Adjusting for physical activity and time of day, higher HR and lower HRV predicted higher self-reported LOC after eating. Parsing between- and within-subjects effects, there was a significant, positive, within-subjects association between pre-meal HR and post-meal LOC rating. However, there was no significant within-subjects effect for HRV, nor were there between-subjects effects for either electrophysiologic variable. CONCLUSIONS: Findings suggest that autonomic indices may either be a marker of risk for subsequent LOC eating or contribute to LOC eating. Linking physiological markers with behavior in the natural environment can improve knowledge of illness mechanisms and provide new avenues for intervention.

Back to the future: Progressing memory research in eating disorders.

OBJECTIVE: Human behaviors, thoughts, and emotions are guided by memories of the past. Thus, there can be little doubt that memory plays a fundamental role in the behaviors (e.g., binging), thoughts (e.g., body-image concerns), and emotions (e.g., guilt) that characterize eating disorders (EDs). Although a growing body of research has begun to investigate the role of memory in EDs, this literature is limited in numerous ways and has yet to be integrated into an overarching framework. METHODS: In the present article, we provide an operational framework for characterizing different domains of memory, briefly review existing ED memory research within this framework, and highlight crucial gaps in the literature. RESULTS: We distinguish between three domains of memory-episodic, procedural, and working-which differ based on functional attributes and underlying neural systems. Most recent ED memory research has focused on procedural memory broadly defined (e.g., reinforcement learning), and findings within all three memory domains are highly mixed. Further, few studies have attempted to assess these different domains simultaneously, though most behavior is achieved through coordination and competition between memory systems. We, therefore, offer recommendations for how to move ED research forward within each domain of memory and how to study the interactions between memory systems, using illustrative examples from other areas of basic and clinical research. DISCUSSION: A stronger and more integrated understanding of the mechanisms that connect memory of past experiences to present ED behavior may yield more comprehensive theoretical models of EDs that guide novel treatment approaches. PUBLIC SIGNIFICANCE: Memories of previous eating-related experiences may contribute to the onset and maintenance of eating disorders (EDs). However, research on the role of memory in EDs is limited, and distinct domains of ED memory research are rarely connected. We, therefore, offer a framework for organizing, progressing, and integrating ED memory research, to provide a better foundation for improving ED treatment and intervention going forward.

The absence of association between anorexia nervosa and smoking: converging evidence across two studies.

Previous studies have found increased smoking prevalence amongst adults with anorexia nervosa (AN) compared to the general population. The current investigation explored bidirectional associations between AN and smoking behaviour (initiation and heaviness), to address questions surrounding causation. In Study One, logistic regression models with variance robust standard errors assessed longitudinal associations between AN and smoking, using data from adolescent participants of the Avon Longitudinal Study of Parents and Children (N = 5100). In Study Two, two-sample Mendelian randomisation (MR) tested possible causal effects using summary statistics from publicly available genome-wide association studies (GWAS). Study One provided no clear evidence for a predictive effect of AN on subsequent smoking behaviour, or for smoking heaviness/initiation predicting later AN. MR findings did not support causal effects between AN and smoking behaviour, in either direction. Findings do not support predictive or causal effects between AN and smoking behaviour. Previously reported associations may have been vulnerable to confounding, highlighting the possibility of smoking and AN sharing causal risk factors.

Individual-, family- and school-based interventions to prevent multiple risk behaviours relating to alcohol, tobacco and drug use in young people aged 8-25 years: a systematic review and meta-analysis.

BACKGROUND: Engagement in multiple substance use risk behaviours such as tobacco smoking, alcohol and drug use during adolescence can result in adverse health and social outcomes. The impact of interventions that address multiple substance use risk behaviours, and the differential impact of universal versus targeted approaches, is unclear given findings from systematic reviews have been mixed. Our objective was to assess effects of interventions targeting multiple substance use behaviours in adolescents. METHODS: Eight databases were searched to October 2019. Individual and cluster randomised controlled trials were included if they addressed two or more substance use behaviours in individuals aged 8-25 years. Data were pooled in random-effects meta-analyses, reported by intervention and setting. Quality of evidence was assessed using GRADE. Heterogeneity was assessed using between-study variance, τ2 and Ι2, and the p-value of between-study heterogeneity statistic Q. Sensitivity analyses were undertaken using the highest and lowest intra-cluster correlation coefficient (ICC). RESULTS: Of 66 included studies, most were universal (n=52) and school-based (n=41). We found moderate quality evidence that universal school-based interventions are likely to have little or no short-term benefit (up to 12 months) in relation to alcohol use (OR 0.94, 95% CI: 0.84, 1.04), tobacco use (OR 0.98, 95% CI: 0.83, 1.15), cannabis use (OR 1.06, 95% CI: 0.86, 1.31) and other illicit drug use (OR 1.09, 95% CI: 0.85, 1.39). For targeted school-level interventions, there was low quality evidence of no or a small short-term benefit: alcohol use (OR 0.90, 95% CI: 0.74-1.09), tobacco use (OR 0.86, 95% CI: 0.66, 1.11), cannabis use (OR 0.84, 95% CI: 0.66-1.07) and other illicit drug use (OR 0.79, 95% CI 0.62-1.02). There were too few family-level (n=4), individual-level (n=2) and combination level (n=5) studies to draw confident conclusions. Sensitivity analyses of ICC did not change results. CONCLUSIONS: There is low to moderate quality evidence that universal and targeted school-level interventions have no or a small beneficial effect for preventing substance use multiple risk behaviours in adolescents. Higher quality trials and study reporting would allow better evidence syntheses, which is needed given small benefit of universal interventions can have high public health benefit. TRIAL REGISTRATION: Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD011374. DOI: 10.1002/14651858.CD011374.

Associations between mealtime anxiety and food intake in anorexia nervosa.

OBJECTIVE: A salient disturbance in anorexia nervosa (AN) is the persistent restriction of food intake. Eating behavior in AN is thought to be influenced by anxiety. The current study probed associations between mealtime anxiety and food intake among individuals with AN and healthy comparison individuals (HC). METHOD: Data were combined across three studies (total of 92 AN and 78 HC) for secondary data analysis. Participants completed a multiitem laboratory buffet meal and visual analogue scale assessments of pre-meal and post-meal anxiety. Linear regression models assessed the association between mealtime anxiety and calorie and fat intake at the meal, and whether associations differed by diagnostic group. RESULTS: Among individuals with AN, pre-meal anxiety was significantly associated with reduced calorie intake and reduced consumption of calories from fat at the meal; these associations were not observed among HC. There was no evidence for an association between calorie/fat intake at the meal and post-meal anxiety in either group. DISCUSSION: Treatments that target mealtime anxiety may improve eating and nourishment among individuals with AN. Interventions like exposure therapy that provide skills in overcoming mealtime anxiety might be enhanced by informing patients that post-meal anxiety is not related to intake.

Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach.

BACKGROUND: Evidence from observational studies suggests an association between anxiety disorders and anorexia nervosa (AN), but causal inference is complicated by the potential for confounding in these studies. We triangulate evidence across a longitudinal study and a Mendelian randomization (MR) study, to evaluate whether there is support for anxiety disorder phenotypes exerting a causal effect on AN risk. METHODS: Study One assessed longitudinal associations of childhood worry and anxiety disorders with lifetime AN in the Avon Longitudinal Study of Parents and Children cohort. Study Two used two-sample MR to evaluate: causal effects of worry, and genetic liability to anxiety disorders, on AN risk; causal effects of genetic liability to AN on anxiety outcomes; and the causal influence of worry on anxiety disorder development. The independence of effects of worry, relative to depressed affect, on AN and anxiety disorder outcomes, was explored using multivariable MR. Analyses were completed using summary statistics from recent genome-wide association studies. RESULTS: Study One did not support an association between worry and subsequent AN, but there was strong evidence for anxiety disorders predicting increased risk of AN. Study Two outcomes supported worry causally increasing AN risk, but did not support a causal effect of anxiety disorders on AN development, or of AN on anxiety disorders/worry. Findings also indicated that worry causally influences anxiety disorder development. Multivariable analysis estimates suggested the influence of worry on both AN and anxiety disorders was independent of depressed affect. CONCLUSIONS: Overall our results provide mixed evidence regarding the causal role of anxiety exposures in AN aetiology. The inconsistency between outcomes of Studies One and Two may be explained by limitations surrounding worry assessment in Study One, confounding of the anxiety disorder and AN association in observational research, and low power in MR analyses probing causal effects of genetic liability to anxiety disorders. The evidence for worry acting as a causal risk factor for anxiety disorders and AN supports targeting worry for prevention of both outcomes. Further research should clarify how a tendency to worry translates into AN risk, and whether anxiety disorder pathology exerts any causal effect on AN.

Anxiety disorders predict fasting to control weight: A longitudinal large cohort study of adolescents.

OBJECTIVE: To determine whether anxiety disorders are prospectively associated with fasting for weight-loss/to avoid weight-gain, a behaviour that precedes and is typical of anorexia nervosa (AN), during adolescence. METHOD: Participants were 2,406 female adolescents of the Avon Longitudinal Study of Parents and Children. Anxiety disorders were assessed when participants were aged 13-14 and 15-16; fasting was measured approximately 2 years after each anxiety assessment. Generalised estimating equation models examined whether anxiety disorders predicted later fasting, across the two longitudinal waves of data. To probe the moderating effect of time, data were stratified by wave and binary logistic regression analyses completed. RESULTS: Across longitudinal waves, anxiety disorder presence predicted increased risk of later fasting. Evidence from wave-stratified analyses supported a positive association between anxiety disorder presence at wave 15-16 and fasting at wave 17-18, however did not indicate an association between anxiety disorders at wave 13-14 and fasting at wave 15-16. DISCUSSION: Anxiety disorder presence in mid-late, but not early, adolescence predicted increased likelihood of later fasting. The differential association could be explained by anxiety being parent-reported at wave 13-14. Findings highlight anxiety disorder pathology as a possible eating disorder prevention target, though the nature of association observed requires clarification.

Prospective associations between childhood neuropsychological profiles and adolescent eating disorders.

OBJECTIVE: Cross-sectional associations between eating disorders (EDs) and deficits in neuropsychological functioning have been well documented; however, limited research has examined whether neuropsychological functioning is prospectively associated with EDs. The current study investigated prospective associations between neuropsychological functioning in childhood (ages 8 and 10) and ED behaviours and disorders in adolescence (at ages 14, 16, and 18 years) in a population-based sample. METHOD: Participants (N = 4,803) were children enrolled in the Avon Longitudinal Study of Parents and Children, a population-based, prospective study of women and their children. Regression methods tested associations between facets of neuropsychological functioning (attention, working memory, and inhibition) and eating disorder symptoms and diagnoses. RESULTS: Better scores on working memory tasks in childhood were associated with decreased risk of fasting but increased risk of excessive exercise during adolescence. Better inhibitory control was associated with decreased risk for disordered eating at age 14, and attentional difficulties were associated with increased risk for binge eating disorder during adolescence among boys but not girls. CONCLUSIONS: Neuropsychological functioning may enhance risk for disordered eating behaviours in specific ways. Overall, effect sizes were small, and results did not support global associations between neuropsychological differences and ED risk in this sample.

Predicting the restrictive eating, exercise, and weight monitoring compulsions of anorexia nervosa.

PURPOSE: Compulsions surrounding restrictive eating, exercise, and weight monitoring are thought to maintain abnormal eating behaviour in individuals with anorexia nervosa (AN). This study aimed to determine if AN psychopathology and trait anxiety explain the presence of restrictive eating, exercise, and weight monitoring compulsions in a mixed sample. METHODS: Participants were 31 females with AN and 31 age and gender-matched healthy individuals (HC). Restrictive eating, exercise and weight monitoring compulsion presence was compared between AN and HC groups. Multivariable poisson regression analyses, adjusted for diagnostic status, were conducted to assess the association of both AN psychopathology and trait anxiety with compulsions across the mixed group. RESULTS: Individuals with AN endorsed a greater number of restrictive eating, exercise and weight monitoring compulsions compared to HC. In adjusted poisson regression analyses neither AN psychopathology nor trait anxiety predicted compulsion presence: incidence rate ratio (IRR) for AN psychopathology = 1.15 [95% CI 0.84, 1.57], p = 0.39; IRR for trait anxiety = 1.01 [95% CI 0.97, 1.06], p = 0.50. CONCLUSIONS: Greater presence of restrictive eating, exercise and weight monitoring compulsions was reported by individuals with AN, supporting the conceptualisation of disorder behaviours as compulsive. The study was underpowered to robustly evaluate the association between predictors of interest and the compulsions outcome, largely owing to the small sample size. Further investigation is required, ideally using methods able to identify causal and mediation effects. LEVEL OF EVIDENCE: Level V, cross-sectional study.

Large-Scale Exploration of Whole-Brain Structural Connectivity in Anorexia Nervosa: Alterations in the Connectivity of Frontal and Subcortical Networks.

BACKGROUND: Anorexia nervosa (AN) is characterized by disturbances in cognition and behavior surrounding eating and weight. The severity of AN combined with the absence of localized brain abnormalities suggests distributed, systemic underpinnings that may be identified using diffusion-weighted magnetic resonance imaging and tractography to reconstruct white matter pathways. METHODS: Diffusion-weighted magnetic resonance imaging data acquired from female patients with AN (n= 147) and female healthy control (HC) participants (n = 119), ages 12 to 40 years, were combined across 5 studies. Probabilistic tractography was completed, and full-cortex connectomes describing streamline counts between 84 brain regions were generated and harmonized. Graph theory methods were used to describe alterations in network organization in AN. The network-based statistic tested between-group differences in brain subnetwork connectivity. The metrics strength and efficiency indexed the connectivity of brain regions (network nodes) and were compared between groups using multiple linear regression. RESULTS: Individuals with AN, relative to HC peers, had reduced connectivity in a network comprising subcortical regions and greater connectivity between frontal cortical regions (p < .05, familywise error corrected). Node-based analyses indicated reduced connectivity of the left hippocampus in patients relative to HC peers (p < .05, permutation corrected). Severity of illness, assessed by body mass index, was associated with subcortical connectivity (p < .05, uncorrected). CONCLUSIONS: Analyses identified reduced structural connectivity of subcortical networks and regions, and stronger cortical network connectivity, among individuals with AN relative to HC peers. These findings are consistent with alterations in feeding, emotion, and executive control circuits in AN, and may direct hypothesis-driven research into mechanisms of persistent restrictive eating behavior.

Food Folio by Columbia Center for Eating Disorders: A Freely Available Food Image Database.

Food images are useful stimuli for the study of cognitive processes as well as eating behavior. To enhance rigor and reproducibility in task-based research, it is advantageous to have stimulus sets that are publicly available and well characterized. Food Folio by Columbia Center for Eating Disorders is a publicly available set of 138 images of Western food items. The set was developed for the study of eating disorders, particularly for use in tasks that capture eating behavior characteristic of these illnesses. It contains foods that are typically eaten, as well as those typically avoided, by individuals with eating disorders. Each image has now been rated across 17 different attributes by a large general United States population sample via Amazon's Mechanical Turk (n = 1054). Ratings included subjective attributes (e.g., tastiness, healthiness, and favorable texture) as well as estimates of nutrient content (e.g., fat and carbohydrate). Each participant rated a subset of stimulus set food items (46 foods) on all 17 dimensions. Additional description of the image set is provided in terms of physical image information and accurate nutritional information. Correlations between subjective ratings were calculated and an exploratory factor analysis and exploratory cluster analysis completed. Outcomes of the factor analysis suggested foods may be described along three latent factors of healthiness, tastiness, and umami taste; the cluster analysis highlighted five distinct clusters of foods varying on these same dimensions. Descriptive outcomes indicated that the stimulus set includes a range of foods that vary along multiple dimensions and thus is likely to be useful in addressing various research questions surrounding eating behavior and cognition in healthy populations, as well as in those with eating disorders. The provision of comprehensive descriptive information allows for stimulus selection that is optimized for a given research question and promotes strong inference.

A systematic review of studies probing longitudinal associations between anxiety and anorexia nervosa.

The current study aimed to establish whether anxiety predicts subsequent anorexia nervosa onset and maintenance. A systematic review of longitudinal studies assessing the association between stable anxiety exposures (e.g. trait anxiety/anxiety disorder pathology) and anorexia nervosa development or maintenance was undertaken. Eight studies met inclusion criteria. Seven probed the association between anxiety and anorexia nervosa onset, and one assessed the association between anxiety and anorexia nervosa maintenance. Individuals with anorexia nervosa were more likely to report childhood anxiety compared to healthy individuals, but whether childhood anxiety explains unique variance in anorexia nervosa development is unclear. Current evidence does not support longitudinal associations between specific anxiety disorders (independently of other anxiety disorders) and subsequent anorexia nervosa onset, however anxiety disorder diagnosis in general may predict increased anorexia nervosa risk. The single study probing the association between anxiety and anorexia nervosa maintenance did not find evidence supporting a relationship. The quality of individual studies was fair to high, however the body of evidence was of low quality. Further research that minimises bias, allowing for strong conclusions concerning longitudinal associations between anxiety and subsequent anorexia nervosa outcomes, is required to inform anorexia nervosa aetiology. This in turn may promote improved prevention and treatment.

What can food-image tasks teach us about anorexia nervosa? A systematic review.

A salient feature of anorexia nervosa (AN) is the persistent and severe restriction of food, such that dietary intake is inadequate to maintain a healthy body weight. Experimental tasks and paradigms have used illness-relevant stimuli, namely food images, to study the eating-specific neurocognitive mechanisms that promote food avoidance. This systematic review, completed in accordance with PRISMA guidelines, identified and critically evaluated paradigms involving images of food that have been used to study AN. There were 50 eligible studies, published before March 10th 2018, identified from Medline and PsychINFO searches, and reference screening. Studies using food image-based paradigms were categorised into three methodologic approaches: neuropsychology, neurophysiology, and functional magnetic resonance imaging (fMRI). Paradigms were reviewed with a focus on how well they address phenomena central to AN. Across tasks, differences between individuals with AN and healthy peers have been identified, with the most consistent findings in the area of reward processing. Measuring task performance alongside actual eating behaviour, and using experimental manipulations to probe causality, may advance understanding of the mechanisms of illness in AN.

Anxiety and the development and maintenance of anorexia nervosa: protocol for a systematic review.

BACKGROUND: Several aetiological models of anorexia nervosa (AN) hold non-eating/weight-gain-related anxiety as a factor relevant to the onset and maintenance of the disorder. Longitudinal studies that allow assessment of this hypothesis have been conducted; however, the evidence has not yet been aggregated in a systematic manner. The proposed study will systematically review articles describing prospective investigations of the relationship between anxiety and AN development or maintenance, with the aim of providing a balanced summary of current understanding and identifying areas for further research. METHODS/DESIGN: Electronic databases will be searched for articles investigating the longitudinal influence of non-eating/weight-gain-related anxiety (anxiety disorders and trait anxiety) on the development/maintenance of AN. References of eligible articles will be searched to ensure the identification of all relevant studies. Two independent reviewers will complete the title and abstract, and full-text, screening, with a third independent reviewer resolving any conflicts at each stage. A systematic review will be completed, and the quality of the included studies, as well as the strength of the body of evidence generated, will be assessed and reported. DISCUSSION: Although there are limitations to the present review, understanding the current evidence for the role of non-eating/weight-gain-related anxiety in AN can direct future research that may ensure accurate aetiological models of AN and effective treatments. SYSTEMATIC REVIEW REGISTRATION: The study is registered on PROSPERO under the reference number CRD42017069644.