Connecting the Dots

“We’re investigating underlying mechanisms in the immune system that may be related to these neuropsychiatric symptoms,” says Juliette Madan, MD, MS, associate professor of psychiatry, of pediatrics, and of epidemiology at Geisel. Madan leads the Neuroimmune Psychiatric Disorders (NIPD) program, a translational research-based clinic taking on this understudied relationship. She works alongside her colleagues Richard Morse, MD, professor of pediatrics and of neurology at Geisel; Mohamed Jasser, DO, a pediatric psychiatrist at Dartmouth Health Children’s; and other subspecialists at the NIPD.

In one NIPD-led research project, Madan and Jasser are collecting longitudinal data and microbiome samples from children who develop PANDAS (pediatric acute-onset neuropsychiatric disorders associated with streptococcus) or the broader category of PANS (pediatric acute-onset neuropsychiatric syndrome), which is linked to infections such as flu or COVID-19. The team is also leading a multicenter study funded by the National Institutes of Health to prospectively identify children who present to their primary care physicians with abrupt-onset neuropsychiatric symptoms and may have PANS. The study intends to clarify the incidence of these conditions and the response to early targeted treatments.

“Our goal is to clarify the relationship between infection, inflammation, immunity, and neuropsychiatric disease to ultimately improve diagnostics and treatment,” Madan says. “Many children get strep, and some children develop OCD, but in which situations are those two things related? That matters because the additional treatments targeting infection and inflammation may provide significant impact.”

The NIPD team, which includes physicians from pediatrics, psychiatry, pediatric neurology, rheumatology, and other specialties, has served more than 500 patients, mostly children, adolescents and young adults, since 2019. The team offers clinical care and invites patients to participate in translational research projects by providing biological data as part of their evaluation and treatment. The program also provides education on neuroimmune psychiatric conditions for trainees, for faculty and primary care colleagues, and for patients and their families. Their clinical, educational, and research programming is supported by organizations such as the Alex Manfull Fund Foundation and the PACE Foundation.

In addition to co-directing the NIPD clinic and leading the research there, Madan works alongside Margaret Karagas, PhD, the chair of epidemiology at Geisel, as a multiple principal investigator for several epidemiological research studies, including the New Hampshire Birth Cohort Study, which is part of the nationwide Environmental Influences on Child Health Outcomes (ECHO)-wide Cohort study. The New Hampshire cohort has enrolled thousands of mother-child pairs to collect data on exposure to environmental contaminants during pregnancy and early childhood to learn how it may affect child health outcomes; Madan’s lab is investigating the neurodevelopmental and neuropsychiatric outcomes in these children, specifically focused on the relationship between exposures and the developing microbiome in relationship to developmental outcomes. In one study, she is researching the relationship between the early-life microbiome and autism spectrum disorder behaviors.

Treatment targeting the cause

Madan hopes her research on PANS, PANDAS, and other neuroimmune psychiatric conditions will bring new insights to primary care physicians (PCPs) treating patients who have debilitating, acute-onset neuropsychiatric symptoms.

Without realizing that neuropsychiatric symptoms can be secondary to an underlying medical condition, a pediatrician unfamiliar with PANS and PANDAS may refer their patient to a psychiatrist without evaluating the child for a primary etiology. And waiting for a psychiatry appointment could delay the right treatment.

However, a physician with knowledge of PANS and PANDAS, and who suspects infection is the cause of the neuropsychiatric symptoms, can refer their patient to the NIPD clinic at Dartmouth Hitchcock Medical Center (DHMC). Then, NIPD physicians can clarify the diagnosis and provide interventions targeting infection or inflammation right away, which can significantly reduce or even eliminate symptoms.

“The multidisciplinary evaluation is rewarding because it’s easy to see often rapid and life-changing results,” Madan says.

The NIPD program will be further empowered by the new six-bed inpatient child psychiatry unit at DHMC, which opened in early April. The new unit increases capacity for the multidisciplinary care of medically complex pediatric patients. “Having the opportunity to provide outpatient as well as inpatient care for patients at Dartmouth will enable our teams to meet a significant unmet need in our region,” Madan says.

Currently, very few multidisciplinary clinics in the U.S. have the expertise to diagnose and treat these illnesses quickly and effectively, and the body of literature on these conditions is just beginning to grow.

Looking to the future, Madan hopes to investigate other secondary neuropsychiatric conditions in teens and young adults who develop psychosis, which also can be triggered by autoimmune conditions. The NIPD clinic currently cares for these patients, and Madan hopes to eventually build a formal research program to study these cases.

“Patients have gotten their lives back because of immune-targeted treatments,” Madan says. “The opportunities to investigate novel treatments targeting the immune system to result in benefit are exciting.”