Epigenetics at Birth Links Microbiome to Neurodevelopment, Potentially ASD and ADHD
The results of a study headed by researchers at Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, indicate that the gut microbiome and epigenetics are intertwined, and that both contribute to neurodevelopment.
The researchers showed that epigenetic changes present at birth can impact how an infant’s gut microbiome develops during their first year. They also identified specific epigenetic changes and gut microbes that were associated with signs of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) when the children were three years old.
“Certain bacteria seem to offer protection, which is exciting because it suggests there could be ways to support a child’s development through diet or probiotics in the future,” said research lead and gastroenterologist Francis Ka Leung Chan, MD. Chan is co-senior author of the team’s published paper in Cell Press Blue, titled “Epigenome-microbiome interplay in early life associates with infants’ neurodevelopmental outcomes,” in which they stated, “We showed that epigenetic alterations at birth were associated with early-life microbiome development and that they determine the risks of neurodevelopmental consequences in children.”
The first years of life are critical for brain development and immune system maturation. Though previous studies have shown that both early epigenetic changes and gut microbiome development can impact health in later life, little is known about how these two systems interact. “Recent data suggest that epigenetic programming of gene expression profiles is sensitive to the early-life environment and can impact health outcomes in children,” the authors wrote. “One environmental cue known to trigger host epigenetic modifications is the genes of bacteria, fungi, and viruses inside the human body, collectively known as the microbiome.”
Co-senior author and public health researcher Hein Min Tun, PhD, of The Chinese University of Hong Kong, commented, “We wanted to see how the epigenome and microbiome interact in early life and if their interaction could influence a child’s risk of developing neurodevelopmental conditions like ASD and ADHD.” The authors added, “New understanding of host-microbe-epigenome interactions and mechanisms of epigenetic changes in early life can be leveraged for the prevention, early detection, and novel interventions of common childhood diseases.”
For their study the researchers characterized DNA methylation patterns from the umbilical cord blood of 571 infants. They paired this information with gut microbiome data collected from 969 infants at two, six, and 12 months of age, and from their parents during the third trimester of pregnancy. When the children reached 36 months of age, the researchers used a behavioral questionnaire to assess their neurodevelopment and investigate links between the microbiome, epigenome, and early signs of ASD and ADHD.
“This, to our knowledge, represents the first longitudinal study with multiple sample types to depict the intimate interplay between perinatal exposures, epigenetic hallmarks, and gut microbiome development and neurodevelopmental outcomes within the first three years of life,” the authors stated.
They found that an infant’s epigenome at birth was associated with birth mode, length of gestation, having older siblings, and maternal allergies, but it was not affected by their parents’ gut microbiomes. Microbiome development, on the other hand, was associated with birth mode, antibiotics, having older siblings, and breastfeeding. Infants who were born by Caesarean section (CS) showed different patterns of DNA methylation for several genes involved in immune responses and brain development. “Some of the changes in methylations of immune- and nervous-system-related genes, associated with CS delivery, are linked to neurodevelopmental outcomes,” they noted.
Their reported findings, the team suggested, “… resonate with studies linking CS to increased risks of immune-mediated and neurodevelopmental disorders, providing mechanistic plausibility through epigenomic and microbial dysbiosis.” The team also showed that an infant’s epigenome at birth impacted how their microbiome developed during their first year. Specifically, infants developed less diverse gut microbiomes at 12 months of age when they showed higher rates of DNA methylation in immune genes involved in recognizing pathogens. “We found that methylation rates in the major histocompatibility complex (MHC) region of infants at birth were linked to differences in the diversity of the infant gut microbiome at 12 months,” they commented.
The behavioral survey revealed that signs of ASD and ADHD in three-year-olds were associated with specific epigenetic patterns and the presence of certain gut microbes. “Importantly, we reported that epigenetic modifications were associated with an increased susceptibility to neurodevelopmental conditions in children, and these effects were in part mediated by microbial colonization.”
However, other microbial species seemed to mitigate these effects: infants with epigenetic patterns associated with ASD or ADHD were less likely to show signs of the disorders if they acquired Lachnospira pectinoschiza and Parabacteroides distasonis, respectively, during their first year. “We discovered a kind of conversation happening: a baby’s epigenetic setting at birth can influence their risk for neurodevelopmental disorders, but the presence of certain ‘good’ bacteria in their gut can step in and modify the risk,” Tun reported. “The foundations for brain health are laid very early, even before birth. However, we don’t want people to think this means a child’s developmental path is fixed at birth. These are complex conditions with many causes, and we’ve only uncovered a small piece of a very large puzzle.”
The researchers are continuing to follow the children who participated in the study to see how these early-life factors relate to their health as they grow. They note that laboratory experiments are needed to confirm the associations between gut microbes and neurodevelopment. In their discussion, the team wrote, “In conclusion, our findings revealed dual alterations to the neonatal epigenome and gut microbiome by perinatal factors and highlight the role of the ‘holo-epigenome’—the integrated host epigenome and microbiome—as a key mediator of neuro-immune outcomes. Interventions targeting microbial restoration or epigenetic modulation during critical developmental windows may mitigate risks of neurodevelopmental disorders.”
First author and gastroenterologist Siew Chien Ng, MD, PhD, added, “The ultimate goal is to develop safe, non-intrusive early interventions such as specific probiotics or live biotherapeutics, that could help nurture a healthy gut microbiome and potentially reduce the risk of neurodevelopmental challenges.”
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In Memoriam: Edna B. Foa, PhD
Dr. Edna Foa served for decades as a professor of clinical psychology in psychiatry at the University of Pennsylvania, where she also directed the Center for the Treatment and Study of Anxiety (CTSA), the internationally renowned program she founded in 1979. Through the CTSA, Edna created not only a hub for groundbreaking research, but also a training ground that would shape the future of evidence-based treatment for anxiety, obsessive compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).
At a time when OCD was poorly understood and often ineffectively treated, Edna helped establish and rigorously validate exposure and response prevention (ERP) as a gold-standard intervention. Building on the early behavioral work of pioneers before her, she brought a level of empirical precision, clinical sophistication, and dissemination that transformed ERP from a promising approach into a cornerstone of modern treatment. In doing so, she fundamentally changed what recovery could look like for millions of people living with OCD.
Her influence extended well beyond OCD. Dr. Foa was also a central figure in the development of cognitive-behavioral models and treatments for PTSD, including prolonged exposure therapy, which has become one of the most widely used and effective interventions for trauma-related disorders. Across both domains, her work exemplified a rare integration of theory, research, and clinical application—always grounded in a singular goal: to reduce suffering and restore lives.
Her connection to the International OCD Foundation (IOCDF) was a natural extension of her commitment to bridging science and real-world impact. Edna was deeply engaged with the IOCDF community over many years, contributing to its mission of improving access to effective treatment and advancing understanding of OCD. The Foundation awarded her with the Outstanding Career Achievement Award in 2011. She was a frequent presence at conferences, where she not only shared her research but also helped elevate the standards of clinical care through teaching, mentorship, and collaboration.
The IOCDF’s growth into a global leader in OCD advocacy, education, and training reflects, in many ways, the scientific foundation that Edna helped build. Her work made it possible for organizations like the IOCDF to promote treatments that are not only evidence-based, but truly life-changing. And through her direct involvement, she helped ensure that the connection between research and practice remained strong, dynamic, and accessible.
Edna Foa showed us what it means to dedicate a life to advancing knowledge in the service of humanity. She illuminated a path forward for so many, and her influence will continue to guide the field for generations to come.
Below are several tributes to Dr. Foa from IOCDF community members.
From Jonathan Grayson, PhD
My mentor, Tom Borkovec, used to talk about our psychological lineage; that in 1979, you only had to go back a few generations of your “forefathers” to reach the founders of American psychology. In this respect, Tom is my psychology father – he taught me to discipline my thinking – he encouraged wild flights of speculation, but to always temper it in print with what could be researched and proved. With this in mind, Edna is my psychology mother. As I noted elsewhere, for all of us who work with OCD, we are her children, grandchildren and so on.
I first met Edna in 1979 at Joseph Wolpe’s Behavior Therapy Unit at Temple University. She hired me as an adjunct research assistant professor. This was in the ancient days at the height of the first wave. There was no cognitive behavioral therapy. ABCT was AABT, American Association of Behavior Therapy. The disorder we were studying was OC, the DSM labeling it obsessive compulsive disorder doesn’t yet exist. Edna was on the first of her landmark OC grants.
She was the flashpoint for all that we do with OCD. Don’t get me wrong, she didn’t invent ERP, but her work was/is the basis of all OCD treatment today. In the same way that cognitive therapy techniques existed before Aaron Beck, but his work was the flashpoint of that second wave; and the techniques of ACT pre-exist Stephen Hayes, but his work and thinking were the flashpoint of the third wave. There was no OC Foundation.
I joined Edna and Gail Steketee and to work with Edna was always a collaboration. So many hours of discussing, designing and analyzing research. Writing papers together often until midnight and beyond. You may have heard that Edna was demanding. She was, but that had nothing to do with the hours we worked. The same clinical skills she used with patients, she used in choosing those who worked with her. We were all driven. There are those who found her direct delivery difficult, but it wasn’t anger or belittling, it wasn’t intimidating (okay, maybe a little), she was simply direct without sugar coating. The truth about Edna was that she was caring and very generous.
As I said, our research was a collaboration and the order of authors on publications reflected our contributions. If you had a research idea that was tangential to her main projects, she would support you. When I told her I thought we should have support groups to help sufferers maintain their gains, I was given a free hand to develop and run GOAL as I saw fit. When my son was nine months old and I told Edna that I was going to change my work hours to: one and a half daytime hours and the rest of my hours after 4 pm, she accepted this. She didn’t have to admonish me or warn me to do my job, Edna knew the kind of people she had chosen. She wanted the people who worked with her to grow. When it came time for me to move on, she was like any parent, sorry for me to go, but happy for me to pursue my life. She was like that with all of us. So many of those who have shaped the OCD world worked with Edna. While I was there, Michael Kozak joined the team and later Edna and Michael published their ground breaking paper on emotional processing. Alec Pollard, Charly Mansueto and Rich McNally also passed through our center. Marty Franklin and Jon Abramowitz came after me making up the many generations of her “children.”
For those whom I’ve neglected to mention, forgive me, but the list is too long. My OCD career began in 1979. Her loss is a hole in the fabric of reality, but her legacy and wisdom lives on through all of us whose OCD psychological lineage can be traced back to Edna Foa.
From Marty Franklin, PhD
I am writing this tribute while waiting at an airport gate for a flight to a national conference. Over the course of the next few days I will have the opportunity to present applied research data, participate in a clinical roundtable about OCD and its treatment, & engage with colleagues as we toss around ideas for how best to move the field forward. Edna’s profound influence on my career, my life, and even my thinking is most often accessible during relatively quiet moments like this, where opportunities for reflection make their way forward amidst the work I have committed to myself to doing. Indeed, I learned of Edna’s passing a few weeks ago while right in the middle of presenting a clinical training about exposure-based treatments for OCD. I paused for a moment to take it all in, but before I could decide how best to proceed under the circumstances, I heard Edna’s voice, in her characteristic and unmistakable Israeli accent, telling me that these clinicians took time out of their busy schedules to receive this training, and therefore I must continue straight through to the end. My feelings? You can process those later. Classic Edna.
My very first day of internship in 1991 at the Medical College of Pennsylvania was spent in Edna’s presence at her Center for the Treatment and Study of Anxiety, the unit she established in 1979 to develop, test, and disseminate cognitive-behavioral interventions for anxiety and related conditions. Edna’s work even by then was highly influential, and her legend was already well in the making. At that initial meeting, Edna slid a formidable stack of old-school medical charts across the table to me and said, “Marty, is it? These are your OCD cases for this rotation.” I thanked her, then asked the first of myriad naïve questions in the legendary Tuesday Meetings: “When will I receive the training to treat these cases?” She pivoted back to look at Michael Kozak, her Clinical Director, as if to wax nostalgic about the process of indoctrinating yet another green intern. Edna then gestured at the pile, and said, “The training is in there.” Edna was a fine clinician too, and thus read well my horrified expression, then offered, “But don’t worry: we’ll help you.” True to her word, she did exactly that.
Edna’s influence on the field broadly speaking, on the development and expansion of cognitive-behavioral theory, on using clinical science to alleviate human suffering, and in pushing the proverbial envelope, has been chronicled elsewhere and cannot ever be overstated. Edna was one of the true pillars of clinical psychology, and the effects of her work will live on in perpetuity, of that I have little doubt. What was less well known except for those of us fortunate enough to have been mentored by Edna was the incredible amount of time and emotional investment she made in seeding the field with the next generation of theorists, scholars, and clinicians who would carry that work forward in the years to come. I count myself in that incredibly lucky group, all of whom were blessed by her personal investment in our training and careers. Edna had exacting standards for herself and for us, and fully expected that same level of investment and intensity on our part. Vigorous debate was just part of the process, where occasionally the fur would fly. But Edna also knew us well enough to understand what each of us needed in order to help us make the commitment needed to join her in the vanguard. In one of our many career development conversations back in the mid 1990s, likely in her East Falls office well after 8 pm, I was fretting about the “soft money” environment of academic psychiatry, and openly wondering if it was time to pivot to hard-line academic psychology or even to private practice. Edna stopped my rumination dead in its tracks, looked into the depths of my soul (which she did regularly), and said, “It’s only soft money if you can’t get it…and I know you can get it. Plus, academia is a really fun way to make a living, and a life.” Edna Foa believed in me: it was about damn time to believe in myself as well, and to make the commitment required to honor that belief. And to always keep pushing to get better at the work, which is truly a never-ending process.
Sitting in this airport now, on my way to give another set of talks on topics I have come to know very well and continue to pursue with the passion that comes from also believing that this work is vital, I concur with Edna’s assessment of academia, and am truly grateful that I listened. Thank you, Edna, for illuminating a path forward for me, as I know you did for countless others. You were unforgettable, and your work will continue on in the hands of those you mentored and trained to carry on the legacy.
From Gail Steketee, PhD, MSW
I had the pleasure and helpful educational challenge of training under Dr. Edna Foa beginning in 1976 and continuing for a decade during which I worked closely with her studying OCD and co-authoring manuscripts and federal grant applications. Edna generously provided me with excellent clinical supervision during my training at the Behavior Therapy Unit at Temple University where I learned how to treat phobias, agoraphobia and panic, and especially OCD. Edna’s encouragement and specific feedback guided my understanding of patients and how to provide effective treatment. Her supervision coincided with the end of her important early study of the impact of exposure and response prevention, following in the steps of Victor Meyer, Isaac Marks, and Jack Rachman. I treated the last few patients with OCD in her study and co-authored a case report stemming from that work – my first published paper in the field in 1977.
Edna opened many doors for me to join colleagues around the world who were studying OCD and behavioral treatment methods. Together we wrote and published 26 papers and 14 book chapters. And I mean “together”. We would schedule writing times during which Edna generated ideas and spoke aloud in her heavily accented Israeli English while I contributed my thoughts and sharpened the language as we went along. Grant applications were a special challenge as NIMH became strict about page limits. More than once we stayed up all night writing grants to meet the deadline – we were both younger then – and once we actually drove to Bethesda to deliver a grant application just in time for the deadline. I joined Edna at many conferences in the U.S. (especially AABT [now ABCT] and OCF [now IOCDF]) and in Europe at EABCT and WCBCT (the World Congress of CBT). We met many delightful OCD researchers and clinicians – it was an exhilarating time. I traveled with Edna and friends to her home country of Israel where she treated us to delightful sights and experiences including the Dead Sea.
The 10 year period with Edna was a heady time as my career unfolded. She supported my decision to get a PhD in social work at Bryn Mawr while working full time with her on our research. Eventually, I left Temple to take a full-time faculty position at Boston University, arriving with a strong publication record already in hand thanks to Edna’s masterful training and modeling of how to design and conduct research, how to write papers that accurately reflected the study and its findings, how to write strong grant applications, and how to connect with energizing colleagues around the world. I am grateful for her mentoring that enabled me to establish my own career and become a mentor to others. She was a brilliant theoretician who spawned impressive thinking and research on OCD, PTSD, behavior therapy, and related topics. Hers was a long and full life. She will be sorely missed.
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In Memoriam: Judith L. Rapoport, MD
Dr. Judith L. Rapoport has left an indelible mark on the field of obsessive compulsive disorder (OCD) — not only through her extraordinary scientific contributions, but through the compassion, curiosity, and humanity she brought to her work. For countless individuals and families, her legacy is not just measured in research breakthroughs, but in hope restored and lives changed.
At a time when OCD was widely misunderstood, often hidden, and rarely discussed, Dr. Rapoport helped bring it into the light. Through her pioneering work at the National Institute of Mental Health, she gave shape and voice to a condition that many struggled to name. She was among the first to recognize that OCD could affect children, and that these young people deserved understanding, accurate diagnosis, and effective care. This insight alone transformed the trajectory of the field and opened doors for earlier intervention and support for families who had long felt alone.
What set Dr. Rapoport apart was not only her intellect, but her deep commitment to the people behind the science. She approached each question with both rigor and empathy, helping to establish treatments that have since become the gold standard, including exposure and response prevention (ERP) and medication. Her work helped shift the narrative—away from blame or misunderstanding, and toward recognition of OCD as a real, treatable medical condition.
Beyond the lab and clinic, Dr. Rapoport had a rare gift for storytelling. Her book, The Boy Who Couldn’t Stop Washing, brought readers into the lived experience of OCD with clarity and care. For many, it was the first time they saw their own struggles reflected with such honesty and dignity. It helped families feel seen, understood, and less alone — an impact that continues to ripple outward today. The Boy Who Couldn’t Stop Washing impacted professionals as well, providing an eye-opening introduction and gateway to the world of working with OCD.
For these accomplishments and more, Dr. Rappaport received the IOCDF’s 2018 Career Achievement Award. Her influence extends through the many clinicians and researchers she has mentored, each carrying forward her dedication to both excellence and empathy. Through them, her work continues to grow, shaping the future of OCD research and care in ways that are both profound and deeply human.
To honor Dr. Judith Rapoport is to honor a career defined not only by discovery, but by kindness and purpose. She helped the world better understand OCD — but more importantly, she helped people living with OCD feel understood. And in doing so, she changed lives in ways that will endure for generations.
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