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Principal Investigator: MICHAEL I MILLER
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $574,378
Funding agency: National Institute of Mental Health
CORE B: ABSTRACT
Core B (Clinical and Imaging Core) will support Projects 1-3 for new clinical and translational research in
schizophrenia (SZ) and relevant animal models. Core B is built on our established cohesive and committed
team of investigators, with experts in clinical enrollment and characterization, olfactory imaging, and cortical
imaging [as a productive outcome of long-term collaboration between the Johns Hopkins Schizophrenia Center
(JHSZC) and the Center for Imaging Science (CIS) at Johns Hopkins University]. Smell deficits are one of the
most reproducible changes in SZ. One key feature of the deficits is their tight association with specific clinical
features, such as negative symptoms (e.g., avolition, anhedonia) and some cognitive deficits (e.g., social
cognitive deficits), but not with positive symptoms (e.g., hallucination, delusion). Since 2009, the NIMH
Research Domain Criteria (RDoC) framework has facilitated studies that focus on neurobiological processes
underlying behavioral domains/constructs, instead of considering each psychiatric diagnosis as one
homogeneous entity. One innovation of this P50 is translational research with both human and mouse studies
under specific behavioral domains/constructs of interest (mainly, positive valence systems and social
processes) in a mechanistic association with the olfactory-prefrontal circuits to account for specific clinical
domains in SZ. Thus, we will leverage the RDoC research framework to organize our research design. Based
on this framework, this Core B will assist Projects in addressing the central hypothesis that, mediated by the
olfactory-prefrontal circuits, molecular and cellular changes in the olfactory epithelium (OE) significantly
contribute to specific clinical manifestations that correlate with smell deficits in SZ patients. Accordingly, Core
B will recruit new study participants and conduct clinical assessments, combining with the existing cohort (Aim
1). We will leverage a recently established alliance of patient recruitment with the Maryland Psychiatric
Research Center (MPRC) and 10 hospitals in the MedStar Health network. We will pay a special attention to
the confounding factors associated with COVID-19 in study participant recruitment and data analysis in
collaboration with Core C (Core for data analysis). Core B will also collect and process brain imaging data
(Aim 2) to provide ex vivo mouse olfactory bulb (OB) imaging (for Project 1), process 3T resting-state
functional magnetic resonance imaging data from human healthy subjects (for Project 2), and obtain 3T
structural imaging of the OB and prefrontal cortex from newly recruited subjects in this grant proposal (for
Project 3). In summary, this Core B will acquire multimodal data from both humans and mice under a specific
scientific focus on the olfactory-prefrontal circuits.
Terms: <Accessory Sinuses><Address><Anhedonia><Animal Model><Animal Models and Related Studies><Anterior><Applications Grants><Appointment><Attention><Behavioral><Biopsy><Blood Sample><Blood specimen><Brain><Brain Mapping><Brain Nervous System><Brain imaging><COVID diagnosis><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 diagnosis><COVID-19 effect><COVID-19 impact><COVID-19 impacted><COVID-19 vaccination><COVID19 diagnosis><CV-19><Cell Body><Cells><Clinic><Clinical><Clinical Research><Clinical Study><Clinical assessments><Cognitive deficits><Collaborations><Collection><Coronavirus Infectious Disease 2019><Data><Data Analyses><Data Analysis><Delusions><Disease><Disorder><Drugs><Dysfunction><Encephalon><Enrollment><Exclusion><Exclusion Criteria><Faculty><Foundations><Functional MRI><Functional Magnetic Resonance Imaging><Functional disorder><Generations><Goals><Grant Proposals><Hallucinations><Health><Hospitals><Human><Image><Infrastructure><Investigators><Lead><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Maryland><Medial><Mediating><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medication><Mice><Mice Mammals><Modern Man><Molecular><Monitor><Murine><Mus><NIMH><NMR Imaging><NMR Tomography><Nasal><Nasal Passages Nose><Nasal Sinuses><Nasal cavity/Paranasal><Nasal cavity/Paranasal sinuses><National Institute of Mental Health><Nerve Cells><Nerve Unit><Neural Cell><Neurobiology><Neurocyte><Neurons><Nose><Nuclear Magnetic Resonance Imaging><Olfaction><Olfactory Epithelium><Olfactory Pathways><Olfactory system><Outcome><Paranasal Sinuses><Participant><Patient Recruitments><Patients><Pb element><Pharmaceutical Preparations><Physicians><Physiopathology><Positive Valence><Prefrontal Cortex><Primary visual cortex><Process><Productivity><Psychiatric Diagnosis><Psychiatrist><Psychiatry><Psychoses><RDoC><Reproducibility><Research><Research Design><Research Domain Criteria><Research Personnel><Researchers><Respiratory System, Nose, Nasal Passages><Rest><SARS-CoV-2 diagnosis><SARS-CoV-2 vaccination><Schizophrenia><Schizophrenic Disorders><Services><Severe acute respiratory syndrome coronavirus 2 vaccination><Sinus><Smell><Smell Perception><Social Processes><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Striate Cortex><Striate area><Study Type><Symptoms><System><Time><Training><Translational Research><Translational Science><Universities><Zeugmatography><area striata><behavioral health><brain visualization><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><cingulate cortex><clinical imaging><cognitive defects><cohort><coronavirus diagnosis><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 diagnosis><coronavirus disease 2019 effect><coronavirus disease 2019 impact><coronavirus disease 2019 vaccination><coronavirus disease diagnosis><coronavirus disease-19><coronavirus disease-19 impact><coronavirus infectious disease-19><data acquisition><data acquisitions><data analysis pipeline><data interpretation><data management><data modeling><data processing pipeline><dementia praecox><diagnosed with COVID><diagnosed with COVID-19><diagnosed with COVID19><diagnosed with SARS-CoV-2><diagnosed with coronavirus><diagnosed with coronavirus 2019><diagnosed with coronavirus disease><diagnosed with coronavirus disease 2019><drug/agent><enroll><experience><fMRI><facilities for imaging><first episode psychosis><heavy metal Pb><heavy metal lead><human data><imaging><imaging center><imaging facilities><imaging science><imaging study><imaging-related facilities><inclusion criteria><innovate><innovation><innovative><interest><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><member><model of animal><model of data><model the data><modeling of the data><multi-modal data><multi-modal datasets><multimodal data><multimodal datasets><neurobiological><neuronal><odor perception><olfactory bulb><olfactory circuitry><olfactory circuits><olfactory perception><participant recruitment><pathophysiology><persistent COVID-19><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><prolonged COVID-19 symptoms><recruit><schizophrenic><secondary outcome><severe acute respiratory syndrome coronavirus 2 diagnosis><social><statistical analysis><structural imaging><study design><translation research><translational investigation><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019>