Eating disorders and the causative role of autoimmunity

Eating disorders are multifactorial; like other psychiatric conditions the causative role of auotimmune neuroinflammation is coming to the fore as evidenced by a study just published in PLoS One (Public Library of Science). The authors note regarding earlier reports relevant to autoimmunity in eating disorders:

"A prior autoimmune disease has recently been shown to increase the risk of mood disorders and schizophrenia. In addition, the risk of both mental disorders increased in a dose response pattern when autoimmune diseases and infections were assessed together. The role of autoimmune processes, such as various pathogens triggering autoantibodies cross-reactive with neuronal antigens (brain-reactive autoantibodies), has also been recognized in the pathogenesis of neuropsychiatric disordersincluding autism spectrum disorders, obsessive-compulsive disorder, tic-disorders, ADHD, post-traumatic stress disorder, and narcolepsy. Furthermore, pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) include anorexia nervosa (AN).""Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder."

Moreover...

"Crohn's disease and celiac disease have been suggested to act as triggers for the development of eating pathology, and individuals with celiac disease are reported to be at increased risk for eating disorders...To our knowledge, no large scale reports of the co-morbidity of autoimmune diseases and eating disorders have been published. "

So they compared 2342 patients with eating disorders compared to 9368 matched controls from the general population and correlated that with data for 30 autoimmune diseases and found a pertinent association:

"Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease. The increase in endocrinological diseases was explained by type 1 diabetes, whereas Crohn's disease contributed most to the risk of gastroenterological diseases. Higher prevalence of autoimmune diseases among patients with eating disorders was not exclusively due to endocrinological and gastroenterological diseases; when the two categories were excluded, the increase in prevalence was seen in the patients both before the onset of the eating disorder treatment and at the end of the follow-up."

Shared immunological mechanisms

In other words, the crucial point is that there are shared immunological mechanisms:

"We observed an increased risk for several autoimmune diseases among patients with eating disorders supporting the hypothesis of co-morbidity of these disorders and suggesting that immune-mediated mechanisms could play a role in the development of eating disorders. Importantly, our results were not restricted to the association of T1D with eating disorders as shown in previous studies. Instead, the association was seen for several autoimmune diseases with different genetic backgrounds. Our findings thus suggest that the link between eating disorders and autoimmune diseases is based on shared immunological mechanisms, rather than on the shared genetic background, e.g. the shared HLA risk genotype. In addition, our findings support earlier observations suggesting that autoimmune processes contribute to the onset and maintenance of eating disorders, at least in a subpopulation of patients."

Chronic inflammation in psychiatric disorders

Chronic inflammation must be assessed in psychiatric disorders:

"Studies indicate that psychiatric disorders co-exist with inflammation, infections and autoimmune diseases, and shared vulnerability underlying many psychiatric disorders suggest that findings from one disorder may be relevant across categories. Pro-inflammatory cytokines and antibodies/autoantibodies against neuronal antigens could induce changes in neurotransmitter and neuroendocrine function, which may subsequently yield psychiatric manifestations. Studies suggest that pro-inflammatory cytokines may have a role in eating disorders."

Pro-inflammatory cytokines

A key clinical point for clinicians, especially those of us who assess serum cytokines, is the fact that they may be elevated in the brain while remaining normal in the blood:

"It has also been suggested that pro-inflammatory cytokines might be overproduced in specific brain areas and act locally without concomitant increase in serum or immune production. Indeed, the pro-inflammatory cytokines are able to activate HPA axis, the hyperactivity of which in eating disorders has been established."

Gut-brain axis

Regarding the role of the gut-brain axis and autoimmunity:

"Our findings are supported by the immunological studies performed in patients with eating disorders, where autoantibodies against peptides related to appetite-regulation, stress response, and social-emotional functioning (α-MSH, ACTH, ghrelin, oxytocin, vasopressin) were detected. The postulated role of intestinal microflora contributing to the development of cross-reactive neuronal autoantibodies provides a link between gut and brain...Gut microbiota is an important regulator of the immune system and its alteration has been associated with autoimmune diseases and immune-mediated disorders, such as allergies and T1D. Composition of the microbiota affects gut permeability, and the function of both innate and adaptive immune system including development of regulatory T-cells."

Sex hormones

Practitioners must also bear in mind that sex hormone dysregulation, as noted earlier here, can contribute to loss of immune tolerance:

"...sex hormones modulate microbiota and the development of autoimmunity, as well as the eating disorders risk. The interplay between gut microbiome, immune regulation, and sex hormones thus provide one potential, complex mechanism underlying eating disorders and explaining the partly shared etiopathogenesis of eating disorders and autoimmune diseases."

Medscape Medical News quotes the lead author:

"I was surprised about the robust link that we found between autoimmune diseases and eating disorders," lead author Anu Raevuori, MD, PhD, from the Department of Public Health at the University of Helsinki, Finland."On the other hand, my clinical impression is that in many patients with eating disorders, particularly those with long-lasting and persistent symptoms, the disorder appears to have a biological background," said Dr. Raevuori."...other lines of research suggest that some of those eating disorder patients that do not have a diagnosable autoimmune disease might have underlying autoimmunological factors, such as autoantibodies against peptides...related to appetite regulation, stress response, and social-emotional functioning, which could explain their symptoms."

Anyone involved in case management for patients suffering from eating disorders should consider the authors' summation:

"In conclusion, we observed the association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our data support the findings from other studies indicating the role of immunological mechanisms at least in a subpopulation of patients with eating disorders. We recommend that clinicians treating patients with eating disorders consider the increased risk of autoimmune diseases and the possible role of autoimmune processes underlying these individuals' somatic and neuropsychiatric symptoms related to mood disturbances, anxiety and disordered eating."