Overcontrol in anorexia nervosa: Elevated prefrontal activity and amygdala connectivity in a working memory task with food distractors.

Individuals with anorexia nervosa (AN) are thought to engage in excessive amounts of self-control, which may contribute to disorder development and maintenance. This "overcontrol" may explain previous findings of increased activity and connectivity in frontal brain regions involved in top-down control functions in response to diverse stimuli including emotionally salient visual food stimuli. However, these observations were made largely in tasks demanding explicit stimulus processing.

Exaggerated frontoparietal control over cognitive effort-based decision-making in young women with anorexia nervosa.

Effortful tasks are generally experienced as costly, but the value of work varies greatly across individuals and populations. While most mental health conditions are characterized by amotivation and effort avoidance, individuals with anorexia nervosa (AN) persistently engage in effortful behaviors that most people find unrewarding (food restriction, excessive exercise). Current models of AN differentially attribute such extreme weight-control behavior to altered reward responding and exaggerated cognitive control.

Dynamic functional connectivity in anorexia nervosa: alterations in states of low connectivity and state transitions.

Background: The onset of anorexia nervosa (AN) frequently occurs during adolescence and is associated with preoccupation with body weight and shape and extreme underweight. Altered resting state functional connectivity in the brain has been described in individuals with AN, but only from a static perspective. The current study investigated the temporal dynamics of functional connectivity in adolescents with AN and how it relates to clinical features.

Triangulating brain alterations in anorexia nervosa: a multimodal investigation of magnetic resonance spectroscopy, morphometry and blood-based biomarkers.

The acute state of anorexia nervosa (AN) is associated with widespread reductions in cortical gray matter (GM) thickness and white matter (WM) volume, suspected changes in myelin content and elevated levels of the neuronal damage marker neurofilament light (NF-L), but the underlying mechanisms remain largely unclear. To gain a deeper understanding of brain changes in AN, we applied a multimodal approach combining advanced neuroimaging methods with analysis of blood-derived biomarkers. In addition to standard measures of cortical GM thickness and WM volume, we analyzed tissue-specific profiles of brain metabolites using multivoxel proton magnetic resonance spectroscopy, T1 relaxation time as a proxy of myelin content leveraging advanced quantitative MRI methods and serum NF-L concentrations in a sample of 30 female, predominately adolescent patients with AN and 30 age-matched female healthy control participants.

Predicting long-term outcome in anorexia nervosa: a machine learning analysis of brain structure at different stages of weight recovery.

Background: Anorexia nervosa (AN) is characterized by sizable, widespread gray matter (GM) reductions in the acutely underweight state. However, evidence for persistent alterations after weight-restoration has been surprisingly scarce despite high relapse rates, frequent transitions to other psychiatric disorders, and generally unfavorable outcome. While most studies investigated brain regions separately (univariate analysis), psychiatric disorders can be conceptualized as brain network disorders characterized by multivariate alterations with only subtle local effects.

Acute tryptophan depletion balances altered resting-state functional connectivity of the salience network in female patients recovered from anorexia nervosa.

Background: It has been suggested that individuals predisposed to or recovered from anorexia nervosa experience a hyperserotonergic state associated with anxiety that might be mitigated by restricted food intake, because diminished levels of the tryptophan precursor lower the central availability of serotonin (5-HT). At the neural level, the salience network is a system of functionally connected brain regions; it has been closely associated with 5-HT functioning and mental disorders (including anorexia nervosa). The aim of the present study was to investigate the effect on the salience network of a temporary dietary manipulation of 5-HT synthesis in patients with anorexia nervosa.

No effects of acute tryptophan depletion on anxiety or mood in weight-recovered female patients with anorexia nervosa.

Background: Previous studies have suggested that individuals recovered from anorexia nervosa (AN) are characterized by increased serotonergic (5-HT) activity that might be related to elevated levels of anxiety. Assuming these traits to be also present in individuals at risk for AN, it was further hypothesized that restricting food intake might be a means to temporarily alleviate dysphoric affective states by reducing central nervous availability of tryptophan (TRP), the sole precursor of 5-HT. One study that supported this hypothesis found anxiolytic effects in individuals with a history of AN during an experimentally induced short-term depletion of TRP supply to the brain.

The effects of acute tryptophan depletion on instrumental reward learning in anorexia nervosa - an fMRI study.

Background: The serotonin (5-HT) hypothesis of anorexia nervosa (AN) posits that individuals predisposed toward or recovered from AN (recAN) have a central nervous hyperserotonergic state and therefore restrict food intake as a means to reduce 5-HT availability (via diminished tryptophan-derived precursor supply) and alleviate associated negative mood states. Importantly, the 5-HT system has also been generally implicated in reward processing, which has also been shown to be altered in AN.

Methods: In this double-blind crossover study, 22 individuals recAN and 25 healthy control participants (HC) underwent functional magnetic resonance imaging (fMRI) while performing an established instrumental reward learning paradigm during acute tryptophan depletion (ATD; a dietary intervention that lowers central nervous 5-HT availability) as well as a sham depletion.

Aberrant neural representation of food stimuli in women with acute anorexia nervosa predicts treatment outcome and is improved in weight restored individuals.

Anorexia nervosa (AN) has been associated with altered reward processing. We recently reported greater neural response in secondary visual areas when processing visual food stimuli in acutely underweight AN patients (acAN). In order to examine whether the observed alterations are indicative of acute undernutrition or a potential trait marker of AN, we set out to assess neural responses in acAN and in individuals weight-recovered from AN (recAN).

Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa.

Background: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals.

Peptide YY concentration in acute- and long-term recovered anorexia nervosa.

Purpose: The gut-brain axis could be a possible key factor in the pathophysiology of anorexia nervosa. The neuropeptide peptide YY, secreted by endocrine L cells of the gastrointestinal tract, is a known regulator of appetite and food intake. The objective of this study was to investigate peptide YY plasma concentrations at different stages of anorexia nervosa in a combined cross-sectional and longitudinal design to differentiate between effects of acute undernutrition and more enduring characteristics.

Metabolic state and value-based decision-making in acute and recovered female patients with anorexia nervosa.

Background: Patients with anorexia nervosa forgo eating despite emaciation and severe health consequences. Such dysfunctional decision-making might be explained by an excessive level of self-control, alterations in homeostatic and hedonic regulation, or an interplay between these processes. We aimed to understand value-based decision-making in anorexia nervosa and its association with the gut hormone ghrelin.

Peripheral serotonin transporter DNA methylation is linked to increased salience network connectivity in females with anorexia nervosa.

Background: Epigenetic variation in the serotonin transporter gene (SLC6A4) has been shown to modulate the functioning of brain circuitry associated with the salience network and may heighten the risk for mental illness. This study is, to our knowledge, the first to test this epigenome–brain–behaviour pathway in patients with anorexia nervosa.

Methods: We obtained resting-state functional connectivity (rsFC) data and blood samples from 55 acutely underweight female patients with anorexia nervosa and 55 age-matched female healthy controls.

Peripheral serotonin transporter DNA methylation is linked to increased salience network connectivity in females with anorexia nervosa.

Background: Epigenetic variation in the serotonin transporter gene (SLC6A4) has been shown to modulate the functioning of brain circuitry associated with the salience network and may heighten the risk for mental illness. This study is, to our knowledge, the first to test this epigenome–brain–behaviour pathway in patients with anorexia nervosa.

Methods: We obtained resting-state functional connectivity (rsFC) data and blood samples from 55 acutely underweight female patients with anorexia nervosa and 55 age-matched female healthy controls.

A naturalistic investigation of cognitive-affective dysfunction in anorexia nervosa: The role of inefficiency.

Objective: Research has shown that rumination and negative affect are elevated in patients with anorexia nervosa (AN), but the underlying origins remain unclear. Drawing from the theoretical framework of the Goal Progress Theory of rumination, we propose that heightened feelings of "inefficiency" (i.e.

Goal-directed vs. habitual instrumental behavior during reward processing in anorexia nervosa: an fMRI study.

Previous studies have proposed that altered reward processing and elevated cognitive control underlie the etiology of anorexia nervosa (AN). A newly debated notion suggests altered habit learning and an overreliance on habits may contribute to the persistence of AN. In weight-recovered AN patients, we previously found neuroimaging-based evidence for unaltered reward processing, but elevated cognitive control.

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 illness, affecting 0.9-4% of women and 0.3% of men, with twin-based heritability estimates of 50-60%.

Abnormal Spontaneous Regional Brain Activity in Young Patients With Anorexia Nervosa.

Objective: Functional magnetic resonance imaging (fMRI) studies have repeatedly shown alterations in patients with anorexia nervosa (AN). These alterations might be driven by baseline signal characteristics such as the (fractional) amplitude of low frequency fluctuations (fALFF/ALFF), as well as regional signal consistency (ie, regional homogeneity [ReHo]) within circumscribed brain regions. Previous studies have also demonstrated gray matter (pseudo-) atrophy in underweight individuals with AN.

Editorial: Connecting the Nodes of Altered Brain Network Organization in Eating Disorders.

Two prevalent eating disorders (ED) in adolescence are anorexia nervosa (AN) and bulimia nervosa (BN). AN is characterized primarily by an extensive restriction of energy intake leading to significantly low body weight. In contrast, the cardinal symptom of BN is uncontrolled eating of an abnormally large amount of food, followed by compensatory behavior to avoid weight gain (eg, self-induced vomiting or laxative abuse).

Editorial: To Eat or Not to Eat: Advancing the Neuroscience of Hedonic Versus Controlled Eating Across Weight and Eating Disorders.

Excessive weight and obesity, especially with childhood onset, is associated with long-term morbidity and mortality and places a major burden on the health care system. In the United States, 17% of children and adolescents are obese (32% overweight). By adulthood, the number rises to 34% or even 68% when also considering overweight individuals.