Principal Investigator

Dani Dumitriu, MD, PhD

Overview

Dani Dumitriu, MD, PhD, is a pediatrician, neuroscientist, environmental health scientist, and Associate Professor of Pediatrics in Psychiatry at Columbia University.

She dedicates 80% of her time to basic science research into the neurobiological basis of resilience, as the Principal Investigator of the DOOR lab (Developmental Origins of Resilience) at the New York State Psychiatric Institute. She dedicates 20% of her time to caring for newborns in the Newborn Medicine Section of the Morgan Stanley Children’s Hospital of New York.

The overarching goal of Dr. Dumitriu's research program is to understand and harness the neurocircuits of resilience to spearhead novel approaches to primary prevention. This is motivated by the observation that during the last century, medicine has made unprecedented progress in the treatment of disease, with a lack of parallel advancement in the prevention of disease. Consequently, the largest current worldwide disease burden comes from preventable mental and physical illnesses, such as depression, anxiety, diabetes, and hypertension. Stressful life events, particularly during critical developmental periods, have been linked to increased risk of virtually all diseases, including metabolic and cardiovascular ones, and a significant effort is underway to understand stress-induced biological consequences. However, even in the presence of the most severe stressors, some individuals remain resistant to the development of stress-induced pathology. Identifying the neurobiological basis for this natural resilience can therefore lead to the development of novel preventative strategies aimed at strengthening resiliency circuits.

To tackle the mechanisms for individual variability in stress-responses, the DOOR lab uses several animal models, with the overarching unifying goal of understanding the structure, function, and Developmental Origins of Resilience. In a mouse model of adult social defeat stress, we dissect preexisting neurocircuit structure-function differences in susceptible versus resilient animals using state-of-the-art tools including in vivo chemogenetics, optogenetics, and miniscope imaging, ex vivo super-resolution imaging of dendritic spines, ex vivo whole-brain imaging of functional or structural connectivity using a variety of genetic and/or viral labeling tools, and graph theoretical analysis of co-activation patterns as a proxy for functional connectomics. In a separate set of experiments, we combine rat early life maternal separation with wireless EEG and/or EKG recordings in dams and their pups. This data is used to understand individual variability in developmental trajectories and the role of dam-pup autonomic synchrony as a potential protective factor. Parallel EKG recordings and synchrony analyses are being conducted during mother-infant interactions in the newborn nursery. Finally, the lab is spearheading a study on wild rat stress-responses, asking the simple question: do depressive-like states occur in the wild, or are they a genetic and environmental epiphenomenon of laboratory breeding. In addition to answering questions about the neurobiological basis for resilience, the DOOR lab is committed to the development of new tools and to the movement toward #openscience. In collaborative work with two different engineering groups, we are developing novel wireless telemetry devices for wild rats and a robotic solution for ex vivo neuronal microinjections. Recently, we also launched a website MouseCircuits.org, as an open science repository of chemogenetic and optogenetic circuit dissection.

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Research

During the last century, medicine has made unprecedented progress in the treatment of disease. In contrast, much less focus has been placed on parallel advancement for the prevention of disease.

Consequently, the largest current worldwide disease burden comes from preventable mental and physical illnesses, such as depression, anxiety, diabetes, and hypertension.

Stressful life events, particularly during critical developmental periods, have been linked to increased risk of virtually all diseases, including metabolic and cardiovascular ones, and a significant effort is underway to understand stress-induced biological consequences. However, even in the presence of the most severe stressors, some individuals remain resistant to the development of stress-induced pathology. Identifying the neurobiological basis for this natural resilience can therefore lead to the development of novel preventative strategies aimed at strengthening resiliency neurocircuits. To tackle the mechanisms for individual variability in stress-responses, the DOOR lab uses multiple animal models, with the overarching unifying goal of understanding the structure, function, and Developmental Origins Of Resilience. In a mouse model of adult social defeat stress, we dissect preexisting neurocircuit structure-function differences in susceptible versus resilient animals using state-of-the-art tools including in vivo chemogenetics, optogenetics, and miniscope imaging, and ex vivo super-resolution imaging of dendritic spines, whole-brain imaging of functional and structural connectivity using a variety of genetic and/or viral labeling tools, and graph theoretical analysis of co-activation patterns as a proxy for functional connectomics. In a separate set of experiments, we combine rat early life stress with wireless EEG/LFP and/or EKG recordings in dams and their pups. These data are used to understand individual variability in developmental trajectories and the role of dam-pup central and autonomic synchrony as a possible protective factor. Parallel EKG recordings and synchrony analyses are being conducted during mother-infant interactions in the newborn nursery. The DOOR lab is also spearheading a study on New York City wild rat stress-responses, asking the simple question: do depressive-like states occur in the wild, or are they a genetic and environmental epiphenomenon of laboratory breeding?

In 2020, the COVID-19 pandemic generated the largest natural experiment in early life stress. The effects of this worldwide event on the “COVID generation” – infants born during the pandemic – are completely unknown. Examination of similar historical events, such as the 1918 Spanish flu, suggests far-reaching repercussions on the future physical and mental health of these individuals across their lifespan. Therefore, in addition to animal models, the DOOR lab spearheaded the COVID-19 Mother Baby (COMBO) Initiative to prospectively document the health and wellbeing of these newborns and their mothers with the ultimate goal of early identification and intervention to ameliorate the negative impact (www.ps.columbia.edu/COMBO).

In addition to answering questions about the neurobiological basis for resilience, the DOOR lab is committed to the development of new tools and to the movement toward open science. In collaborative work with two different engineering groups, we are developing novel wireless telemetry devices for wild rats and a robotic solution for single neuron microinjections. Recently, we also launched an online resource, MouseCircuits.org (link is external and opens in a new window), as an open science repository of chemogenetic and optogenetic circuit dissection.

Clinical Trials

NCT number: NCT04531618

Brief Summary:

The purpose of this study is to compare the mother-infant emotional connection formed during the pandemic in standard care (SC) versus Family Nurture Intervention (FNI) pairs, an evidence-based intervention designed to counteract the adverse effects of maternal-infant disconnection. In prior research on preterm infants in the neonatal intensive care unit (NICU), FNI participants demonstrated increased quality of maternal caregiving behaviors and significant improvements in premature infants' neurodevelopment across multiple domains, including social-relatedness and attention problems. Goals of FNI include assisting mothers in providing appropriate types of stimulation for their babies that are important for social, emotional, and neurobehavioral development as well as reducing stress physiology in both mother and infant. Data gathered in this study will help the investigators learn more about the underlying mechanisms that take place during mother-infant interactions and examine how these play a role in setting the infant up for the best neurodevelopmental trajectory. Intervention will be conducted electronically both in the Well Baby Nursery (WBN) and at home over the following 4 months. Assessments will consist of videos of mother-infant interactions at the time of each intervention session, and pediatrician-led follow-up surveys conducted in the linked Institutional Review Board-approved study.

Detailed Description:

Mother-infant interactions, which are well-established to strongly influence long-term neurodevelopmental outcomes, are at particular risk during the pandemic, both due to maternal stress, as well as to changes in health care policies leading to decreased interaction with healthcare providers during the immediate postpartum period. In order to minimize risk of severe acute respiratory syndrome (SARS)-CoV-2 transmission, nurses and physicians in the WBN have minimized entry and exit into patient rooms, and new moms are discharged on average one day early. In addition to psychological stress, there are also currently unknown risks to the neonates born to mothers with SARS-CoV-2 infections at various points in their pregnancy. Although viral transmission itself seems unlikely, it is currently completely unknown if secondary effects will be observed. In the case of maternal HIV infection, it is now well established that even when vertical transmission does not occur, there are negative consequences to neurodevelopmental outcomes of these exposed children. It is therefore imperative to develop preventive strategies that protect newborns and set them on the path of optimal neurodevelopment. As mother-infant nurturing interactions are known to be the most crucial ingredient in optimal neurodevelopmental trajectories, the goal of the investigators is to test the hypothesis that an intervention focused on promoting mother-infant emotional connection in the neonatal period will lead to long-term benefit and prevention of deleterious effects of the COVID-19 pandemic. The investigators will use FNI, an intervention specifically developed to enhance mother-infant emotional connection through facilitated mother-infant interactions, emotional exchanges and mutual calming sessions. Some of the facilitated interactions include: interactive touch with deep emotional expression and vocal soothing, sustained reciprocal olfactory exposure, family practice in comforting, and skin-to-skin holding. Previously at CUIMC, an RCT investigated the effects of FNI in NICU infants. Infants who received FNI showed significant increases in electroencephalogram (EEG) power, a measure of brain activity, near term age compared with those who receive Standard Care (SC). Increased EEG power has previously been shown to be associated with improved cognitive development, as measured by the Bayley Scales of Infant and Toddler Development (BSID-III). Within the group of children who scored above 85 on the Bayley-III (1 standard deviation below the mean or higher), FNI infants scored significantly higher on the BSID-III Cognitive and Language scales compared to SC infants. Additionally, FNI infants had lower risk for autism spectrum disorder (ASD) as measured by the Modified Checklist of Autism for Toddlers (M-CHAT), an early ASD screening questionnaire. FNI infants also displayed significantly lower levels of EEG coherence (1-18 Hz) largely within and between frontal regions. This finding suggests that FNI may accelerate brain maturation, particularly in frontal brain regions, which are involved in regulation of attention, cognition, and emotion. Taken together, the first RCT of FNI is strongly suggestive of neurodevelopmental benefit.Purpose/aims: The COVID-19 pandemic has made precautions necessary in the Well Baby Nursery that result in maternal stress which is known to impair mother-infant bonding, which is well-established to be critical for positive long-term neurodevelopmental and behavioral outcomes. The investigators will be conducting a randomized controlled trial (RCT) of Family Nurture Intervention (FNI) in the Morgan Stanley Children's Hospital (MSCH) Well Baby Nursery (WBN) at Columbia University Irving Medical Center (CUIMC). The RCT will compare neurodevelopmental and socio-emotional outcomes of the current standard of care (SC) during the COVID-19 pandemic with Family Nurture Intervention (FNI) conducted via telemedicine.