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Principal Investigator: Christoph Juchem
Organization: COLUMBIA UNIVERSITY HEALTH SCIENCES
Fiscal Year: 2022
Award: $1,094,475
Funding agency: National Institute of Mental Health
While 1 in 5 children are at risk for psychiatric disorders, only 1 in 20 young children receive mental health care.
There remains a gap in knowledge of early causes and precursor symptoms of psychiatric disorders; therefore,
many children are not identified as at risk until school age, when a diagnosis can reliably be made. Prenatal
maternal immune activation (MIA) from infection, stress, medical conditions, and environmental pathogens has
been associated with offspring risk of psychiatric disorders. There remains a gap in our knowledge of the early
brain and behavioral antecedents of this risk. Preclinical studies suggest that MIA may lead to biochemical
changes in the developing brain that disrupt brain-behavior functional associations. We propose to examine
whether prenatal exposure to MIA leads to metabolic and functional modifications in the developing brain and
analogous behavioral phenotypes in human offspring. Our prior work demonstrated that MIA (interleukin-6; IL-
6) was associated with functional connectivity of the salience network (SAN), a network integral for emotion
regulation, in neonates. Extending this, we will conduct longitudinal magnetic resonance imaging (MRI) scans in
fetuses, neonates, and infants to determine if the alterations in the SAN originate in the fetal period and map
developmental trajectories of the SAN in early life. In tandem, we plan to collect longitudinal magnetic resonance
spectroscopy (MRS), which provides mechanistic information about the metabolic and cellular properties that
may correspond to disruptions of SAN functional activity. Our pilot data suggests that MIA is associated with
myo-inositol, an indicator of astroglial cell activation, in the newborn brain. Our central hypothesis is that MIA,
evidenced by levels of inflammation (primary: IL-6) and infection (primary: Total immunoglobulin G), is associated
with brain connectivity and metabolites in the SAN and behavioral reactivity from the fetal to infancy periods.
One hundred and seventy-five pregnant women-fetal dyads will participate in this study from 12 weeks gestation
to 9 months postnatal life. The pregnant women will have blood draws and psychological assessments at three
timepoints and fetal physiologic assessment and MRI at 33-36 weeks. The infants will participate in MRI (2-6
weeks and 4 months postnatally) and observer-based behavioral paradigms at 4- and 9-months of age. Our
proposal uses a collaborative science approach, bringing together perinatal-developmental neuroscience
(Marisa Spann), psychoneuroimmunology (Staci Bilbo), maternal-fetal medicine (Mirella Mourad), and
quantitatively trained biomedical engineers in the areas of developmental functional imaging and data science
(Dustin Scheinost) and MRS (Christoph Juchem). This proposal is significant because it will provide mechanistic
and system levels information about the rapidly developing brain that map on to an important behavioral system,
emotion regulation. This research has the potential to reveal trajectories of behavioral health in early childhood
and present approaches to detect early markers of psychiatric risk.
Terms: <(TNF)-α><0-11 years old><0-4 weeks old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><3-10C><3rd trimester><7S Gamma Globulin><AMCF-I><Age><Age-Months><Anterior><Area><Astrocytes><Astrocytus><Astroglia><Autism><Autistic Disorder><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Behavior><Behavioral><Behavioral Paradigm><Beta Proprotein Interleukin 1><Biochemical><Biological><Biomedical Engineering><Blood><Blood Reticuloendothelial System><Brain><Brain Nervous System><Brain region><COVID-19 virus><COVID19 virus><CTLA-8><CTLA8><CXCL8><Cachectin><Cell Body><Cells><Cells Placenta-Tissue><Central Lobe><Child><Child Youth><Children (0-21)><Chiro-Inositol><Clinical><CoV-2><CoV2><Cord Blood><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><Cytotoxic T-Lymphocyte-Associated Antigen 8><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8><Data><Data Collection><Data Science><Development><Diagnosis><Discipline of obstetrics><Disease Frequency Surveys><Dorsal><Early Infantile Autism><Encephalon><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Exposure to><Fetus><Functional Imaging><Future><GCP1><Gaussian Distribution><Generalized Growth><Gestation><Goals><Grippe><Growth><Gynecology><HPGF><Head circumference><Health><Hepatocyte-Stimulating Factor><Human><Hybridoma Growth Factor><IFN-beta 2><IFNB2><IL-1 beta><IL-1 β><IL-1-b><IL-17><IL-17A><IL-1β><IL-6><IL-8><IL1-Beta><IL1-β><IL17 Protein><IL17A><IL1B Protein><IL1F2><IL1β><IL6 Protein><IL8><IL8 gene><IgG><Immune><Immune Cell Activation><Immune Markers><Immunes><Immunoglobulin G><Immunologic Markers><Infant><Infantile Autism><Infection><Inflammation><Inflammatory><Influenza><Inositol><Insula><Insula of Reil><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8)><Interleukin 17 Precursor><Interleukin 1beta><Interleukin-1 beta><Interleukin-17><Interleukin-1β><Interleukin-6><Island of Reil><K60><Kanner's Syndrome><Knowledge><Last Trimester><Lead><Learning Disabilities><Learning disability><Left><Level of Evidence><Life><Link><Long-term prospective studies><Longitudinal prospective study><Longterm prospective studies><MGI-2><MR Imaging><MR Spectroscopy><MR Tomography><MRI><MRI Scans><MRIs><Macrophage-Derived TNF><Magnetic Resonance Imaging><Magnetic Resonance Imaging Scan><Magnetic Resonance Spectroscopy><Maps><Maternal-fetal medicine><Measures><Medical><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mental Health Services><Mental Hygiene Services><Mental disorders><Mental health disorders><Mesoinositol><Metabolic><Modern Man><Modification><Monocyte-Derived TNF><Motor><Myeloid Differentiation-Inducing Protein><NIMH><NMR Imaging><NMR Tomography><National Institute of Mental Health><Neonatal><Neurosciences><Newborn Infant><Newborns><Normal Distribution><Normal Placentoma><Normal Statistical Distribution><Nuclear Magnetic Resonance Imaging><Obstetrics><Pathway interactions><Pb element><Perinatal><Peripartum><Physiologic><Physiologic Imaging><Physiological><Pilot Projects><Placenta><Placenta Embryonic Tissue><Placentome><Plasmacytoma Growth Factor><Population><Pregnancy><Pregnant Women><Preinterleukin 1 Beta><Premature Infant><Process><Property><Psychiatric Disease><Psychiatric Disorder><Psychoneuroimmunology><Psychosocial Stress><Public Health><RDoC><Reporting><Research><Research Domain Criteria><Risk><Rodent><Rodentia><Rodents Mammals><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SCYB8><Schizophrenia><Schizophrenic Disorders><School-Age Population><Science><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Spottings><Stimulus><Stress><Structure><System><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><TSG-1><Temperament><Third Pregnancy Trimester><Third Trimester><Time><Tissue Growth><Training><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Umbilical Cord Blood><Variant><Variation><Work><Wuhan coronavirus><Zeugmatography><ages><astrocytic glia><autism spectrum disorder><autistic spectrum disorder><b-ENAP><base><behavior phenotype><behavior response><behavioral health><behavioral phenotyping><behavioral response><bio-engineered><bio-engineers><bioengineering><biologic><biological engineering><brain behavior><cognitive control><cohort><coronavirus disease 2019 virus><coronavirus disease-19 virus><dementia praecox><developmental><early childhood><emotion regulation><emotional regulation><endophenotype><epidemiologic investigation><epidemiology study><expectant mother><expecting mother><experience><exposed in utero><fetal><fetal cord blood><fetal exposure><fetal reactivity><hCoV19><heavy metal Pb><heavy metal lead><imaging science><immune activation><immune-based biomarkers><immunological biomarkers><immunological markers><in utero exposure><in vivo><indexing><individual heterogeneity><individual variability><individual variation><infancy><infantile><infants born premature><infants born prematurely><interest><interferon beta 2><intra-uterine environmental exposure><intrauterine environmental exposure><mental health care><mental healthcare><mental illness><metabolic profile><nCoV2><neonatal period><neonate><neural><neurobehavior><neuron development><neuronal development><newborn child><newborn children><offspring><ontogeny><pathogen><pathway><physiological imaging><pilot study><postnatal><pre-clinical study><preclinical study><pregnant mothers><premature baby><premature infant human><prenatal><prenatal exposure><prenatally exposed><preterm baby><preterm infant><preterm infant human><psychiatric illness><psychiatric symptom><psychologic><psychological><psychological disorder><psychoneuroimmunological><public health relevance><recruit><relating to nervous system><response><schizophrenic><school age><unborn><youngster>