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Principal Investigator: Meghann Ryan
Organization: UNIVERSITY OF MARYLAND BALTIMORE
Fiscal Year: 2024
Award: $37,490
Funding agency: National Institute of Mental Health
Project Summary
In the USA, SARS-CoV-2 has infected more than 16 million children and adolescents, who are undergoing critical
periods of brain development when higher cognitive abilities are acquired, and mental illnesses typically emerge.
Autopsy, blood, and CSF studies during acute COVID-19 reported neuroinflammation, which can alter cerebral
white and gray matter morphometry, microstructure, and brain function. These brain alterations are associated
with elevated risks for cognitive deficits and mental illness. A major gap in our current knowledge exists in
understanding how SARS-CoV-2 infection during adolescence may impact brain structure and function and
consequently, cognition and mental health. To address this gap, we will utilize pre-/post-pandemic neuroimaging,
cognitive, and psychiatric symptom data from the Adolescent Brain Cognitive Development (ABCD) Study®. We
will test the overall hypothesis that neuroinflammation during acute SARS-CoV-2 infection leads to brain
changes that are detectable on MRI, including lasting alterations in macro and microstructural and
functional abnormalities, which in turn mediate poorer cognitive performance and mental health. In Aim
1, we will identify morphometric (on structural MRI) and microstructural (on diffusion tensor imaging)
abnormalities associated with SARS-CoV-2 infection by comparing longitudinal MRI data between those with
(COVID+) and without a prior documented COVID-19 history (COVID-) to evaluate group differences on cortical
thickness, cortical surface areas, subcortical volumes, and microstructural measures across baseline, year 2
and year 4 follow-up visits. Aim 2 will determine whether SARS-CoV-2 infection alters brain function using the
Emotional N-Back task. We will longitudinally compare brain activation patterns and performance scores
between the COVID+ and COVID- groups. Aim 3 will evaluate whether SARS-CoV-2 infection is associated with
increased risks for neurobehavioral abnormalities. We will use data from the NIH Toolbox® Cognitive Battery
and Kiddie Schedule for Affective Disorders and Schizophrenia 5 to longitudinally compare cognitive
performance and anxiety/depression prevalence between the two groups. Lastly, mediation analyses will be
performed to assess the direct and indirect impact of changes in brain structure and function on cognition and
mental health. For all Aims, sex differences and sex-specific effects will be evaluated. Throughout this 3-year
project, I will be supported by my sponsor, Dr. Linda Chang, and my co-sponsors, Drs. Amal Isaiah, Gloria
Reeves, and Thomas Ernst, who will provide interdisciplinary expertise and training to me in the areas of COVID-
19, neuroimaging, neurodevelopment, cognitive assessments, clinical research, MRI data processing and
analyses, data mining, and adolescent psychiatry. Furthermore, my training will be sufficiently supplemented
with coursework, seminars, career workshops, conferences, and mentorship opportunities to allow me to fully
develop into a well-rounded, independent investigator in clinical neuroimaging research.
Terms: <0-11 years old><12-20 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><Active Follow-up><Acute><Address><Adolescence><Adolescent><Adolescent Psychiatry><Adolescent Youth><Adult><Adult Human><Affective Disorders><Age><Ammon Horn><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Anisotropy><Anterior><Anxiety><Area><Astrocytes><Astrocytus><Astroglia><Astroprotein><Autopsy><Axon><Back><Behavioral><Blood><Blood Reticuloendothelial System><Brain><Brain Nervous System><Brain region><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 crisis><COVID-19 effect><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 impact><COVID-19 impacted><COVID-19 infection><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 virus><COVID-19 virus infection><COVID-19 years><COVID19 infection><COVID19 virus><CV-19><Cell Density><Cerebrospinal Fluid><Cerebrum><Child><Child Youth><Children (0-21)><Clinical><Clinical Research><Clinical Study><CoV-2><CoV2><Cognition><Cognitive><Cognitive Manifestations><Cognitive Symptoms><Cognitive deficits><Cornu Ammonis><Coronavirus Infectious Disease 2019><DWI (diffusion weighted imaging)><DWI-MRI><Data><Data Analyses><Data Analysis><Demyelinations><Detection><Development><Differences between sexes><Differs between sexes><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Dorsum><Dysfunction><Early Intervention><Educational workshop><Emotional><Emotional Depression><Encephalon><Enrollment><Face><Female><Fiber><Functional MRI><Functional Magnetic Resonance Imaging><Functional disorder><GFA-Protein><GFAP><Glial Fibrillary Acid Protein><Glial Fibrillary Acidic Protein><Glial Intermediate Filament Protein><Hippocampus><History><Hortega cell><Hospital Admission><Hospitalization><Image><Immediate Memory><Infection><Inflammatory><Investigators><Knowledge><Leanness><Light><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Maps><Measurement><Measures><Mediating><Mediation><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mental Depression><Mental Health><Mental Hygiene><Mental disorders><Mental health disorders><Mentorship><Microglia><Mood Disorders><Multimodal Imaging><Myelin><NIH><NMR Imaging><NMR Tomography><National Institutes of Health><Negotiating><Negotiation><Nerve Cells><Nerve Degeneration><Nerve Unit><Neural Cell><Neural Development><Neurobehavioral Manifestations><Neurobehavioral Signs and Symptoms><Neurocyte><Neurologic Effect><Neuron Degeneration><Neurons><Nuclear Magnetic Resonance Imaging><Parents><Participant><Patients><Pattern><Performance><Phase><Photoradiation><Physiopathology><Predisposition><Prevalence><Psychiatric Disease><Psychiatric Disorder><Psychological Health><Puberty><Radial><Radius><Recording of previous events><Reporting><Research><Research Personnel><Researchers><Risk><Rodent><Rodentia><Rodents Mammals><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sample Size><Schedule><Schizophrenia><Schizophrenic Disorders><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><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 coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Sex Differences><Sexual differences><Shapes><Short-Term Memory><Shortterm Memory><Site><Structural defect><Structural malformation><Structure><Surface><Susceptibility><Swelling><Testing><Thick><Thickness><Thinness><Training><United States><United States National Institutes of Health><Visit><Workshop><Wuhan coronavirus><Youth><Youth 10-21><Zeugmatography><active followup><acute COVID-19><acute SARS-CoV-2 infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adolescence (12-20)><adulthood><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><age associated><age associated alterations><age associated changes><age correlated><age correlated alterations><age correlated changes><age dependent><age dependent alterations><age dependent changes><age group><age linked><age related><age related alterations><age related changes><age specific><age specific alterations><age specific changes><ages><alterations with age><amygdaloid nuclear complex><anxiety symptoms><anxious symptom><astrocytic glia><axon damage><axon injury><axonal damage><axonal injury><biological sex><brain abnormalities><brain health><career><cerebral><cerebral spinal fluid><changes with age><cognitive ability><cognitive assessment><cognitive control><cognitive defects><cognitive development><cognitive function><cognitive performance><cognitive testing><cognitive training><computerized data processing><conference><convention><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 crisis><coronavirus disease 2019 effect><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 impact><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 impact><coronavirus disease-19 pandemic><coronavirus disease-19 virus><coronavirus infectious disease-19><critical period><dMRI><data interpretation><data mining><data processing><datamining><dementia praecox><demyelinate><depression><depression symptom><depressive><depressive symptoms><developmental><diffusion tensor imaging><enroll><executive control><executive function><fMRI><faces><facial><follow up><follow-up><followed up><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><followup><gitter cell><glial activation><glial cell activation><gray matter><hCoV19><hippocampal><histories><imaging><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><juvenile><juvenile human><kids><life span><lifespan><male><mental illness><mesoglia><microglial cell><microgliocyte><morphometry><mortality><multi-modal imaging><multi-modality imaging><multimodality imaging><myelination><nCoV2><necropsy><neural degeneration><neural imaging><neural inflammation><neuro-imaging><neurobehavioral><neurobehavioral symptom><neurodegeneration><neurodegenerative><neurodevelopment><neurofilament><neuroimaging><neuroinflammation><neuroinflammatory><neurological degeneration><neurological imaging><neuronal><neuronal degeneration><non-human primate><nonhuman primate><parent><pathophysiology><perivascular glial cell><post SARS-CoV-2 infection><post-pandemic><postmortem><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><psychiatric illness><psychiatric symptom><psychological disorder><schizophrenic><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><spinal fluid><structural abnormalities><structural anomalies><substantia alba><substantia grisea><summit><symposia><symposium><synaptic pruning><water diffusion><white matter><white matter change><working memory><youngster>