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News

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Anorexia Nervosa in the

Context of PANS/PANDAS

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An interview with Lauren Breithaupt, PhD

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By Alyssa Weninger

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Lauren Breithaupt is a clinical researcher and research fellow exploring the connections between PANS/PANDAS1 and eating disorders with a primary focus on the overarching question: can we identify individuals who are at risk?

Breithaupt obtained her Ph.D. in clinical psychology with an emphasis in neuroscience from George Mason University. While at the University, she received two National Science Foundation fellowships: the first was to study the underlying neurobiological mechanisms involved in eating disorders, and the second was to study metabolomics and genetics in individuals with Anorexia Nervosa. During the second fellowship, Breithaupt moved to Stockholm, Sweden for a year to pursue research and training at Karolinska Institute under the direction of Dr. Cynthia Bulik – a professor at both Karolinska Institute and University of North Carolina at Chapel Hill.

Using the nation-wide Swedish registers, a database of public health records, she studied the hypothesis that immune dysregulation contributes to psychiatric mental illness and how that could fit with autoimmune

1 Neuroimmune disorders that occur upon infection; group A Strep specifically for PANDAS

disorders. Her research suggested that one has a greater risk for developing an eating disorder both pre and post autoimmune diagnosis. In addition, she states: “Having an eating disorder puts you at a greater risk for an autoimmune disease, and having an autoimmune illness also puts you at greater risk for an eating disorder.” She ponders further: “If we see these bidirectional relationships existing, then there is probably some underlying biology that’s driving this which could be immune-related or overall neuroinflammation.”

Once back in the U.S., she worked for a company that tests for pathogens, and here, she narrowed her research to the PANS/PANDAS subtype of Anorexia Nervosa. Upon receiving many calls from families inquiring if they could send in blood or stool samples to test for traces of an underlying infection, an indicator of PANS/PANDAS, she grew curious about the disorder. She wondered why PANS/PANDAS caused OCD in some but anorexia in others, so she began to take her research in that direction. She researched the risk of developing an eating disorder after an individual has an infection and “what might change and what is driving this relationship.”

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After working with the Swedish register, she decided to utilize the Danish register to continue her research by investigating the risk of developing an eating disorder following an infection. Expanding on her earlier work that demonstrated a link between autoimmune disease and eating disorders, she found in the Danish register that there is a significant increase in risk for developing an eating disorder following a bacterial infection. The biological basis for this connection and how we identify patients with neuroimmune dysfunction as an underlying cause is now the subject of active research by Dr. Breithaupt and others.

While the correlation between eating disorders and PANS/PANDAS was not made prominent until very recently, Breithaupt’s research suggests that “at least half the patients with PANS or PANDAS actually at some point in time will develop into restrictive eating.” However, while restrictive eating in a PANS/PANDAS context is gaining more awareness, she also states: “I think right now it’s really focused on restriction, but I’ve worked with individuals who also engage in binge eating or purging behaviors as well. The loose epidemiological evidence suggests that that’s there,


and now more and more it seems like I’m seeing some individuals with other types of eating pathology in a PANS or PANDAS context.”

In order to investigate her question of who may be at risk, Breithaupt first studied which type of restrictive eating disorders are most prevalent in people with PANS/PANDAS. Avoidant Restrictive Food Intake Disorder (ARFID), is a disorder in which an individual fears contamination or has sensory and sensitivity aversions to certain foods due to a fear of adverse consequences. This disorder seems to mimic classic OCD, so at first, she thought she would see more cases of ARFID than Anorexia Nervosa in the context of PANS/PANDAS. However, while she did encounter many individuals displaying ARFID symptoms, she also witnessed restrictive eating due to the fear of weight gain and body image obsessions. Since ARFID was not included in the diagnostic and statistical manual for disorders or the ICD codes, there was no way for a medical provider to code that this was a disorder. Therefore, research on ARFID in the context of infections has been minimal, but from working with individuals, Breithaupt finds both subtypes of restrictive eating relatively equally common.

Since discovering the presence of these subtypes, Breithaupt has been attempting to answer: what is the progression of symptoms in a child with PANS/PANDAS and how does it differ from individuals with OCD and anorexia without PANS/PANDAS? In order to study these questions more closely, she is currently working on a proposal for the Radcliffe Institute at Harvard. However, in terms of her own experiences working with individuals, she tends to see the infection followed by OCD symptoms and then eating disorder symptoms. She discusses this relationship: “I think one thing that’s really interesting is that it could be that the OCD symptoms are already there and then the eating disorder symptoms develop. It could be that these individuals are sort of at risk for perseverating on certain thoughts.”

That eating disorder symptoms often occur in the later stages of the illness, or when the child gets older, may indicate that puberty plays a role in the progression. However, she has also witnessed individuals who have a pre-pubescent onset of eating disorder symptoms, indicating that this timeline may not be purely due to puberty or environmental factors. Breithaupt states: “With the PANS/PANDAS subtype,

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you can see OCD symptoms come on earlier than a typical course of OCD. And with eating disorders, while puberty is a key onset time, there are individuals with an earlier onset and now the question is: is there this subtype of PANS/PANDAS with restrictive eating, and in those individuals do we see earlier onset of both disorders?”

The differences in age of onset prompted the question of what factors contribute most to the onset of symptoms. Interestingly, seemingly common experience, such as a diet or strep-infection, both contribute with varying levels to eating disorders and PANDAS. However, Breithaupt observes that “Everyone has shape and weight concerns at some point in time, and that’s sort of the norm for both men and women, but not everyone develops an eating disorder. And then another thing that had me totally hooked in on PANS/PANDAS is that everyone develops strep, but not everyone develops OCD or any type of eating disorder as a result of that.” As she puts it, “I’m studying two things that are common with relatively uncommon outcomes.” She hypothesizes that there may be some environmental contributions, but those are not the sole cause of these illnesses, and they may coexist with other factors. She


speculates that a changing environment may allow OCD symptoms to become eating disorder symptoms, but those symptoms were not a result of the environment in the first place. She found evidence for the lack of environmental influence on the development of symptoms because within the PANS/PANDAS subtype, anorexia is not as heavily weighted towards females who typically receive more of the societal pressures of beauty standards and therefore would seemingly be more likely to develop restrictive eating patterns. She recognizes: “The pressure is there, and it definitely contributes, but it’s not the key driver.” Breithaupt speculates that for PANS/PANDAS, these eating disorder symptoms would develop with or without beauty standards but those pressures could affect the timing of onset.

Breithaupt is currently investigating what other factors could be coexisting with the environment to cause these symptoms. She states: “The genetic research on Anorexia Nervosa suggests that there’s a huge overlap between Anorexia Nervosa and OCD,” so she wants to understand the underlying biology for both OCD and anorexia as well as for PANS/PANDAS.

She continues: “So if the genetics are really similar between the two disorders (OCD and anorexia), then perhaps it is that there is this sort of environmental pull that we see in a subset or it could be something underlying from the beginning and it just happens to be that puberty might be the point that then you see the eating disorder symptoms come on.” The similarities between OCD and anorexia both symptomatically and genetically suggest that anorexia may be a different manifestation of the same underlying biology of OCD.

In relation to how OCD and anorexia are tied, some of her research working with patients suggests that when attempting to treat the OCD symptoms, the anorexia symptoms can worsen and patients can lose more weight. Likewise, when attempting to treat the anorexia symptoms, the OCD symptoms tend to worsen. This research prompts the question of how and when should a medical professional decide which symptoms to target? Breithaupt recognizes that there are cognitive-behavioral treatments (CBT) and family treatments that work for a variety of individuals with eating disorders, and exposure therapy for OCD, but

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there is no suggested treatment plan for individuals who have eating disorder subtypes of PANS/PANDAS. In some instances, she has seen some success by using the same types of treatment as one would for general OCD or eating disorders. However, in these cases of success, the individuals have and are aware of their PANS/PANDAS diagnosis, they have medication management, exposure treatment for the OCD, but are still struggling at a low weight. She speaks to the need for some form of identifier for PANS/PANDAS because “for individuals for whom treatment for anorexia has been very hard she wonders if there is an underlying infection that should be treated first.”

In the future, she wants to look at PANS/PANDAS longitudinally in order to determine the course of illness to hopefully be able to identify a prodromal stage to catch the illness early. To do this, she needs to identify when the infection occurred, when the symptoms developed, and what the longterm course of illness looks like. However, it is a challenge to identify when the infection occurred because frequently, people with PANDAS do not present


classic strep symptoms and only notice their infection once the psychological symptoms arise.

The key to identifying a prodromal stage and answering Breithaupt’s main research question of how to identify individuals at risk likely lies in the establishment of a biomarker. A biomarker could be found in a blood test; however, scientists must have enough blood samples from individuals with and without PANS/PANDAS to observe what differs between sick and healthy patients. Another type of biomarker could be found through imaging, to see how structural activity or inflammatory markers might differ between healthy patients and individuals with PANS/PANDAS. In addition, cerebrospinal fluid samples would help researchers determine what may cross the blood-brain barrier. However, to obtain these samples and images, people with PANS/PANDAS, eating disorders, and healthy controls must be willing to participate in and learn about research in this field. She speaks to the establishment of a biomarker: “To me, that would indicate a lot of progress in a field that isn’t able to identify individuals at risk.”

To address the complexity of this illness while establishing a biomarker, Breithaupt states: “I think in general we need people from different backgrounds coming together because to figure this one out, it is going to take clinical psychologists, psychiatrists, immunologists, and basic cell biologists.” Clinical researchers need to figure out the course of illness in order to design studies to intervene at different time points, but immunologists and cell biologists will have the skills to analyze the clinical researchers’ results and determine what next to study. For the eating disorder subtype of PANS/PANDAS, it would be helpful to bring together both eating disorder experts and PANS/PANDAS experts to start by deciding on the first level of treatment and later which symptoms to target when and how. This line of research is still in its infancy, so in order to progress, it is essential to attract more researchers to the field and demonstrate the importance of participating in research to patients and families.

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