Mount Sinai’s first recipient of the National Institute of Mental Health’s T32 postdoctoral research fellowship, Training the New Generation of Clinical Neuroscientists: Vahe Khachadourian, MD, PhD.
A large body of research suggests that environmental exposures during pregnancy may be associated with autism in offspring. But those studies barely scratch the surface of the complex task of understanding the cause of autism spectrum disorders. At the Icahn School of Medicine at Mount Sinai, postdoctoral fellow Vahe Khachadourian, MD, PhD, and his mentor Magdalena Janecka, PhD, are working to solve that intricate puzzle.
Dr. Janecka is an assistant professor of psychiatry and heads the Functional Epidemiology lab at the Seaver Autism Center at the school of medicine. Dr. Khachadourian was Mount Sinai’s first recipient of the National Institute of Mental Health’s T32 postdoctoral research fellowship, Training the New Generation of Clinical Neuroscientists.
With support from this prestigious fellowship and mentorship from Dr. Janecka and others at Mount Sinai, Dr. Khachadourian is helping to paint a more complete picture of the environmental exposures that affect pregnant people and their developing children.
Pregnancy Exposures and Autism: What Is the Connection?
Dr. Khachadourian trained as a physician before receiving a PhD in epidemiology. His current research focuses on the intersection of psychiatric and physical disorders — a topic that fits squarely within Dr. Janecka’s interests. “My lab is focused on early life and parental risk factors for neurodevelopmental disorders,” she said. That focus takes two tracks: “We want to learn how different exposures in pregnancy are associated with future autism risk in the child, and also better understand how different exposures in pregnancy relate to each other,” she added.
Dr. Khachadourian’s first project in the Functional Epidemiology lab focused on the latter of those goals, exploring patterns of co-occurring mental and physical health problems in a population sample of pregnant women in Israel. He found a significantly higher burden of physical problems among pregnant women with a mental health diagnosis than in those without—higher even than the rate of comorbid physical conditions, suggesting distinct links between physical and mental health during pregnancy. The physical symptoms ranged across disease states, including neurological, gastrointestinal, and musculoskeletal diseases. This work, currently pending publication, was presented at the Society of Biological Psychiatry conference last year.
The high co-occurrence of mental and physical symptoms has implications for both pregnancy outcomes and child health outcomes such as autism, Dr. Khachadourian said. In other studies, he has started to dig into the implications for autism risk. One analysis explored a variety of factors that pregnant women may be exposed to, such as preterm birth, hypoxia, infections, and trauma during pregnancy, as well as medical comorbidities, including depression, anxiety, obesity, sleeping problems, and attention-deficit/hyperactivity disorder. He and his colleagues looked for patterns among comorbidities in pregnant women and possible associations with autism in their babies. The study also incorporated data from siblings who did not have autism, to tease out which environmental exposures are most likely to contribute to the development of autism.
“If we know women have had [certain] exposures, we may be able to prevent some comorbidities, and we may be more likely to screen for and diagnose autism in their offspring earlier,” he says. “Of course, identifying these unique patterns may also help us to better understand the etiology of autism spectrum disorders.”
In other ongoing work using population samples, Dr. Khachadourian is analyzing health registry data from Denmark and Israel to examine the links between maternal medication use and psychiatric and physical diagnoses and autism in their offspring. “When it comes to autism, there are studies that have examined maternal exposures, but most have focused on one or a few diagnoses rather than systematically evaluating the wide range of diagnoses a mother can have during pregnancy. That is one unique aspect of our work,” he said. “Another aspect is that we use a relatively large sample and combine family design to try to tease out some of the confounding factors and begin to tease out some of the correlation from causation.”
These projects are exploratory in nature. While they are not designed to identify causal relationships between maternal exposures and autism, Dr. Khachadourian and Dr. Janecka hope they will point toward possible clues that warrant further study.
Fellowship Research in Functional Epidemiology
The T32 postdoctoral fellowship is designed to train clinician-scientists to formulate original research questions surrounding the etiology, pathogenesis, treatment, and prevention of neurological disorders, with the goal of bridging the gap between neurobiology research and clinical disease. The structured program includes a number of core training courses and workshops, as well as a dedicated mentoring team. Ultimately, the fellowship aims to translate research into better patient care “Whenever we think about conducting a study, we always think about the implications for both clinical practice and for future research,” Dr. Khachadourian said.
The fellowship has been a rich opportunity for Dr. Khachadourian and for Mount Sinai, Dr. Janecka said, providing dedicated funding and establishing Dr. Khachadourian as an NIH-funded early-career scientist. The research has been so successful, she added, that the fellowship has been extended a third year.
That research partnership is helping to chip away at the complex factors that influence autism risk. “A lot of studies show the association of this or that with future autism spectrum disorder. But we still don’t know why,” Dr. Janecka said. “We are trying to combine several different approaches, and several different data sets, to better understand the role of the environment in autism.”