The Neurobiology of Anorexia Nervosa

Anorexia nervosa is considered the most deadly psychological illness. Individuals with and recovered from anorexia nervosa experience numerous physical and mental health difficulties, and treatment outcomes remain unpromising. Anorexia nervosa is rare in the general population, but common among individuals with a first-degree relative with the disorder. In addition, the onset of anorexia nervosa is developmentally specific, which suggests a partly biological etiology. A better understanding of the biological and neurobiological etiology of anorexia nervosa is direly needed to inform new therapies and to identify individuals at risk for the disorder. This paper summarizes the research related to neurotransmitter abnormalities, aberrant brain activity, and genetic and epigenetic mechanisms that may contribute to the etiology of this deadly disorder

Children at high-familial risk for Eating Disorders: study of psychopathology, neuropsychology and neuroimaging

Evidence suggest that a diagnosis of an eating disorder (ED) is associated with differential neurocognitive functioning and neural mechanisms. However, whether differences are present prior to the onset of the disorder (‘trait’), possibly affecting risk status for development of an ED; or whether differences are a consequence of secondary features of the disorder such as low nutritional intake (‘state’), is not clear. Family studies have established that first-degree relatives of individuals with ED are at higher risk of developing an ED than the general population, therefore, children of mothers with an ED (current or history) are the perfect group to study risk pathways to developing ED. This is the first study to explore neural alterations as well as neurocognitive functioning in girls at high-familial risk of developing an ED, in comparison to children who are not. High risk status of girls were defined using a maternal clinical interview to confirm lifetime ED diagnosis. Intelligence, social cognition, reward responsiveness, neuropsychological function and brain imaging were investigated in girls at high-familial risk. Girls at high familial risk demonstrated difficulties in set-shifting (cognitive flexibility) and increased reward responsiveness when compared to girls at low risk. Girls at risk also had overall increased Gray matter (GM) volume, and specifically increased GM in amygdala, caudate, hippocampus and orbitofrontal cortex when compared to girls at low risk. There were no differences in white matter (WM) connectivity from amygdala to areas of the cortex in girls at risk compared to girls at low risk. Results suggest that differences observed may constitute putative intermediate phenotypes for ED, although this requires further study with larger samples. Findings are important as they support hypothesis of altered set-shifting as an endophenotype for ED. They also provide evidence of alterations in ventral (limbic) neurcircuit that includes the amygdala and caudate, both of which are of importance for identifying emotional stimuli and generation of affective response to these as well as playing a role in reward processes and behaviour regulation

Structural Neuroimaging of Anorexia Nervosa: Future Directions in the Quest for Mechanisms Underlying Dynamic Alterations.

Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation and extreme weight loss. Pseudoatrophic brain changes are often readily visible in individual brain scans, and AN may be a valuable model disorder to study structural neuroplasticity. Structural magnetic resonance imaging studies have found reduced gray matter volume and cortical thinning in acutely underweight patients to normalize following successful treatment. However, some well-controlled studies have found regionally greater gray matter and persistence of structural alterations following long-term recovery. Findings from diffusion tensor imaging studies of white matter integrity and connectivity are also inconsistent. Furthermore, despite the severity of AN, the number of existing structural neuroimaging studies is still relatively low, and our knowledge of the underlying cellular and molecular mechanisms for macrostructural brain changes is rudimentary. We critically review the current state of structural neuroimaging in AN and discuss the potential neurobiological basis of structural brain alterations in the disorder, highlighting impediments to progress, recent developments, and promising future directions. In particular, we argue for the utility of more standardized data collection, adopting a connectomics approach to understanding brain network architecture, employing advanced magnetic resonance imaging methods that quantify biomarkers of brain tissue microstructure, integrating data from multiple imaging modalities, strategic longitudinal observation during weight restoration, and large-scale data pooling. Our overarching objective is to motivate carefully controlled research of brain structure in eating disorders, which will ultimately help predict therapeutic response and improve treatment

Voxel-Based Morphometry Reveals Brain Gray Matter Volume Changes in Successful Dieters

Objective: To compare regional brain volume predictors of percent weight loss (WL) in dieters with obesity (DwO) and in the same participants categorized as “successful” (≥7% WL) or “unsuccessful” dieters

Life on a scale:Deep brain stimulation in anorexia nervosa

Anorexia nervosa (AN) is a severe psychiatric disorder marked by low body weight, body image abnormalities, and anxiety and shows elevated rates of morbidity, comorbidity and mortality. Given the limited availability of evidence-based treatments, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN

Neurobiological and metabolic mechanisms of binge-eating in anorexia and bulimia nervosa

Binge-eating is characterised by the recurrent consumption of large amounts of food, which co-occurs with a subjective loss of control over intake. This transdiagnostic syndrome results in significant distress, functional impairment and comorbidity. However, precise characterisation of the physiological and neurobiological mechanisms that give rise to, or maintain, this behaviour is lacking. This thesis integrates observations across metabolic, neural and behavioural levels in women with and without eating disorders, providing novel insights into how perturbations across each strata interact with one another in illness and in health to shape eating behaviour. In Chapter 1, I review the classification of binge-eating disorders prior to summarising the extant literature on homeostatic and non-homeostatic mechanisms that influence (ab)normal eating behaviour. This introductory chapter also reviews current perspectives on how psychological stress influences disordered eating, outlining the motivation for the multimodal neuroimaging protocol detailed in Chapter 2. Chapter 2 focuses on the specific methodology of this neuroimaging study, which examined the impact of acute, psychological stress on gut hormones, endocrine responses, and inhibitory control in women acutely ill with the binge-eating and purging subtype of anorexia nervosa, bulimia nervosa and matched controls. Chapters 3 through 5 report the results of this study. Chapter 3 focuses on findings of dissociable hormonal responses to stress in anorexia and bulimia nervosa, presenting novel evidence that links acute changes in mental state to altered gut hormone signalling in anorexia nervosa. Chapter 4 is dedicated to the functional magnetic resonance imaging arm of the protocol, which rigorously examined the impact of diagnosis and induced stress on two forms of response inhibition: proactive and reactive control. Chapter 5 provides insight into associations between peripheral metabolic markers and neural integrity of the cerebral cortex in patients and controls. Finally, Chapter 6 provides a brief summary, discusses the implications of these findings and presents some ongoing and future research that extends this original work. In summary, this thesis represents, to my knowledge, the first attempt to generate a multi-level framework for understanding the physiological and psychological mechanisms of illnesses characterised by binge-eating. Findings identify important metabolic and neurobiological distinctions between two eating disorders with shared symptomatology, demonstrating the need for, and value in, integrative models of mental illness.Cambridge International Trust; NIH Oxford Cambridge Scholars Progra

Social cognition in anorexia nervosa: Evidence of preserved Theory of Mind and impaired emotional functioning.

The findings of the few studies that have to date investigated the way in which individuals with Anorexia Nervosa (AN) navigate their social environment are somewhat contradictory. We undertook this study to shed new light on the social-cognitive profile of patients with AN, analysing Theory of Mind and emotional functioning. Starting from previous evidence on the role of the amygdala in the neurobiology of AN and in the social cognition, we hypothesise preserved Theory of Mind and impaired emotional functioning in patients with AN.Thirty women diagnosed with AN and thirty-two women matched for education and age were involved in the study. Theory of Mind and emotional functioning were assessed with a set of validated experimental tasks. A measure of perceived social support was also used to test the correlations between this dimension and the social-cognitive profile of AN patients.The performance of patients with AN is significantly worse than that of healthy controls on tasks assessing emotional functioning, whereas patients’ performance is comparable to that of healthy controls on the Theory of Mind task. Correlation analyses showed no relationship between scores on any of the social-cognition tasks and either age of onset or duration of illness. A correlation between social support and emotional functioning was found. This latter result seems to suggest a potential role of social support in the treatment and recovery of AN.The pattern of results followed the experimental hypothesis. They may be useful to help us better understand the social-cognitive profile of patients with AN and to contribute to the development of effective interventions based on the ways in which patients with AN actually perceive their social environment