3/25/2015 11:00:13 AM
Image Credit: JAMA, ©AMA
Large Study Finds GI Symptoms Appear in Infancy and Persist Through Age 3
NEW YORK (March 25, 2015)—Scientists at Columbia University’s Mailman School of Public Health report that children with autism spectrum disorder (ASD) were two-and-a-half times more likely to have persistent gastrointestinal (GI) symptoms as infants and toddlers than children with typical development. Results are published in JAMA Psychiatry.
The study is based on a large longitudinal survey of Norwegian mothers who were asked about their child’s GI disturbances during the first three years of life. Questionnaires were completed when the children were 18 and 36 months of age.
The authors found that children with ASD had higher odds of their mothers reporting constipation and food allergy/intolerance in the 6- to 18-month-old age range, and higher odds of diarrhea, constipation, and food allergy/intolerance in the 18- to 36-month-old age range compared with children with typical development.
Mothers of children with ASD were also more likely to report one or more GI symptoms in their children in either or both age ranges compared with mothers of children with typical development. And children with ASD were more likely to have GI symptoms than children with developmental delay, suggesting that the disturbances were not simply secondary to developmental delay associated with autism.
“We not only learned that these symptoms appeared early in infancy; we also found that children with ASD were at significantly increased risk for these symptoms to persist compared with typically developing children,” says Michaeline Bresnahan, PhD, first author and assistant professor of Epidemiology at the Mailman School.
“The longitudinal nature of the study allowed us to uncover the presence of GI complaints in early life—before mothers knew their child would be diagnosed with autism,” says Ezra Susser, MD, DrPH, co-senior author and professor of both Psychiatry and Epidemiology at the Mailman School and Columbia University Medical Center. “This is yet another demonstration of how longitudinal cohort research can shed light on features of autism.”
GI-Autism Relationship Remains Unclear
While higher rates of GI symptoms are associated with autism, Dr. Bresnahan cautions that “the vast majority of children with these symptoms won’t go on to develop autism, nor do all people with autism have GI problems as children.” Bresnahan adds, “GI symptoms alone need not be cause for alarm.”
“Although the connection of GI disturbances to autism remains unclear, the presence of GI symptoms in early life may not only help to identify a subset of children with autism who require clinical input for their GI issues, it may also open new avenues for determining the underlying nature of the disorder in that subgroup,” notes Mady Hornig, MD, co-first author of the study and associate professor of Epidemiology at the Mailman School.
“Delineating factors that disrupt signaling along the gut-brain axis while the brain is still under development may ultimately provide a key to understanding how the disorder occurs in the subset of children with autism and GI complaints,” adds W. Ian Lipkin, MD, the study’s senior author, and John Snow professor of Epidemiology and director of the Center for Infection and Immunity at the Mailman School.
Additional co-authors include Andrew F. Schultz from the Mailman School; Nina Gunnes, Kari Kveim Lie, Per Magnus, Ted Reichborn-Kjennerud, Christine Roth, Synnve Schjølberg, Camilla Stoltenberg and Pål Surén from the Norwegian Institute of Public Health; and Deborah Hirtz from the National Institute of Neurological Disorders and Stroke.
The research was supported by the Norwegian Ministry of Health and Care Service, the Norwegian Ministry of Education and Research, and grant NS47537 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. The authors report no conflicts of interest.
About Columbia University’s Mailman School of Public Health
Founded in 1922, Columbia University’s Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master’s and doctoral degree programs. The Mailman School is also home to numerous world-renowned research centers including ICAP (formerly the International Center for AIDS Care and Treatment Programs) and the Center for Infection and Immunity. For more information, please visit www.mailman.columbia.edu.
2/25/2015 11:25:51 AM
Immune signatures in blood point to distinct disease stages, open door to better diagnosis and treatment
NEW YORK (Feb. 27, 2015)—Researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health identified distinct immune changes in patients diagnosed with chronic fatigue syndrome, known medically as myalgic encephalomyelitis (ME/CFS) or systemic exertion intolerance disease. The findings could help improve diagnosis and identify treatment options for the disabling disorder, in which symptoms range from extreme fatigue and difficulty concentrating to headaches and muscle pain.
These immune signatures represent the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder, and the first evidence that the disease has distinct stages. Results appear online in the new American Association for the Advancement of Science journal, Science Advances.
With funding to support studies of immune and infectious mechanisms of disease from the Chronic Fatigue Initiative of the Hutchins Family Foundation, the researchers used immunoassay testing methods to determine the levels of 51 immune biomarkers in blood plasma samples collected through two multicenter studies that represented a total of 298 ME/CFS patients and 348 healthy controls. They found specific patterns in patients who had the disease three years or less that were not present in controls or in patients who had the disease for more than three years. Short duration patients had increased amounts of many different types of immune molecules called cytokines. The association was unusually strong with a cytokine called interferon gamma that has been linked to the fatigue that follows many viral infections, including Epstein-Barr virus (the cause of infectious mononucleosis). Cytokine levels were not explained by symptom severity.
“We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn't psychological,” states lead author Mady Hornig, MD, director of translational research at the Center for Infection and Immunity and associate professor of Epidemiology at Columbia’s Mailman School. “Our results should accelerate the process of establishing the diagnosis after individuals first fall ill as well as discovery of new treatment strategies focusing on these early blood markers.”
There are already human monoclonal antibodies on the market that can dampen levels of a cytokine called interleukin-17A that is among those the study shows were elevated in early-stage patients. Before any drugs can be tested in a clinical trial, Dr. Hornig and colleagues hope to replicate the current, cross-sectional results in a longitudinal study that follows patients for a year to see how cytokine levels, including interleukin-17A, differ within individual patients over time, depending on how long they have had the disease.
Stuck in High Gear
The study supports the idea that ME/CFS may reflect an infectious “hit-and-run” event. Patients often report getting sick, sometimes from something as common as infectious mononucleosis (Epstein-Barr virus), and never fully recover. The new research suggests that these infections throw a wrench in the immune system’s ability to quiet itself after the acute infection, to return to a homeostatic balance; the immune response becomes like a car stuck in high gear. “It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,” says Dr. Hornig. “Early diagnosis may provide unique opportunities for treatment that likely differ from those that would be appropriate in later phases of the illness.”
The investigators went to great lengths to carefully screen participants to make sure they had the disease. The researchers also recruited greater numbers of patients whose diagnosis was of relatively recent onset. Patients’ stress levels were standardized; before each blood draw, patients were asked to complete standardized paperwork, in part to engender fatigue. The scientists also controlled for factors known to affect the immune system, including the time of day, season and geographic location where the samples were taken, as well as age, sex and ethnicity/race.
In 2012, W. Ian Lipkin, MD, director of the Center for Infection and Immunity, and colleagues reported the results of a multicenter study that definitively ruled out two viruses thought to be implicated in ME/CFS: XMRV (xenotropic murine leukemia virus [MLV]-related virus) and murine retrovirus-like sequences (designated pMLV: polytropic MLV). In the coming weeks, Drs. Hornig and Lipkin expect to report the results of a second study of cerebrospinal fluid from ME/CFS patients. In separate ongoing studies, they are looking for “molecular footprints” of the specific agents behind the disease—be they viral, bacterial, or fungal—as well as the longitudinal look at how plasma cytokine patterns change within ME/CFS patients and controls across a one-year period, as noted above.
“This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in ME/CFS and diagnostic biomarkers for disease,” says senior author W. Ian Lipkin, MD, also the John Snow Professor of Epidemiology at Columbia’s Mailman School. “The question we are trying to address in a parallel microbiome project is what triggers this dysfunction.”
Co-authors include Andrew F. Schultz, Xiaoyu Che, and Meredith L. Eddy at the Center for Infection and Immunity; Jose G. Montoya at Stanford University; Anthony L. Komaroff at Harvard Medical School; Nancy G. Klimas at Nova Southeastern University; Susan Levine at Levine Clinic; Donna Felsenstein at Massachusetts General Hospital; Lucinda Bateman at Fatigue Consultation Clinic; and Daniel L. Peterson and Gunnar Gottschalk at Sierra Internal Medicine. The authors report no competing interests.
Support for the study was provided by the Chronic Fatigue Initiative of the Hutchins Family Foundation and the National Institutes of Health (AI057158; Northeast Biodefense Center-Lipkin).
About Columbia University’s Mailman School of Public Health
Founded in 1922, Columbia University’s Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master’s and doctoral degree programs. For more information, please visit www.mailman.columbia.edu.
If you would like support CII's ME/CFS research, please click on: https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677
Coverage of these findings appeared in the New York Times, Wall Street Journal, Reuters, BBC, Business Insider, US News and World Report, New York Magazine, the New Yorker, the Atlantic, Huffington Post, Fox News, Telegraph, Science Times, CTV, the Columba University and Columbia University Medical Center homepages and other media outlets.
In loving memory of Vanessa Li.
2/12/2015 11:33:41 AM
February 11, 2015—The Center for Infection and Immunity (CII) at the Mailman School and the Department of Agriculture of the Kingdom of Saudi Arabia have formalized a $2.8 million agreement to train scientists in advanced methods for diagnosis and surveillance of infectious diseases, including the Middle East Respiratory Virus, better known as MERS, which has infected 965 people, of whom 357 have died.
“Since the start of the MERS outbreak in 2012, we have worked closely with Saudi scientists to determine the animal origins of MERS. This agreement will ensure that scientists there have the specialized training needed to address the ongoing outbreak and build the country’s capacity to face other infectious threats in the future,” said W. Ian Lipkin, director of CII.
Over the next two years, CII faculty in New York will provide classroom and practical, hands-on training for twelve Saudi scientists in methods for detecting infectious agents. In addition, CII will provide onsite technical support for Saudi laboratories and training for technicians.
CII and Saudi scientists were the first to report evidence of MERS coronavirus in bats and camels. Their findings led to interventions that have reduced the risk of new transmission to humans. As part of the new two-year agreement, CII will continue to study MERS in Saudi Arabia to determine whether the virus is carried in pets, including dogs and cats.
Lipkin and Sami S. Alnohait, Assistant Deputy Minister for Animal Resources in the Saudi Ministry of Agriculture, signed the agreement on February 10.