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Principal Investigator: Megan E Huibregtse
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $81,784
Funding agency: National Institute of Mental Health
PROJECT SUMMARY
Women experience worse symptoms and outcomes following traumatic brain injury (TBI), contrary to the
consensus in preclinical research that female sex hormones confer neuroprotection. Multiple mechanisms
have been proposed to drive this health disparity, including hormonal fluctuations during the menstrual cycle
and into the menopausal transition, a predisposition to seek medical attention or report symptoms, and
increased neurobiological vulnerability to injury. In particular, increased vulnerability to mechanical trauma in
female axons and the role of neurosteroid hormones have not been thoroughly examined in human TBI.
While mild traumatic brain injuries (mTBI) make up the majority of TBIs, research often focuses on a specific
sub-type of mTBI: sports-related concussions. However, many people experience head trauma during a
traumatic event, such as motor vehicle collisions, physical assault, sexual assault, or falls, and the lifetime
prevalence of experiencing at least traumatic event is extremely high (90%). As the literature on sports-related
concussions may not always generalize to this trauma-exposed population, we aim to characterize sex
differences in structural and functional connectivity (Aim 1), examine sex-dependent associations between TBI
pathophysiology and outcomes (Aim 2), and finally assess the influence of concurrent estradiol levels on TBI
outcomes and neuroimaging markers (Aim 3) To address these aims, I will leverage a large, existing dataset
from the AURORA study, a multisite, longitudinal study of posttraumatic outcomes. Participants were recruited
to AURORA if they presented to a participating Emergency Department (ED) within 72 hours of a qualifying
traumatic event and then were followed through 12-months posttrauma. Participants were assessed using a
multidimensional range of tools and measures to general a one-of-a-kind, rich dataset to study the complex,
co-occurring symptoms and overlapping neural correlates of adverse posttraumatic neuropsychiatric sequelae
across a variety of disciplines. About one-third of AURORA participants met modified American Congress of
Rehabilitation Medicine criteria for TBI. However, as the acute and chronic stress responses can mask and
compound signs and symptoms of TBI, it is essential to use an objective marker to establish TBI in this trauma-
exposed cohort. We propose to use ED GFAP levels to identify individuals with TBI, which have shown to be
significantly elevated in individuals with TBI for several days following presentation at the ED. TBI outcomes
will include not only somatic symptoms (e.g., headache, sensitivity to light) but also PTSD and depression
symptoms and mental health-related quality of life. Completion of this project will not only inform our
understanding of neurobiological factors that affect sex differences in TBI outcomes but also provide excellent
postdoctoral training for the applicant in diffusion magnetic resonance imaging, resting-state functional
connectivity, neuroendocrinology, PTSD and stress-related psychopathology, and biostatistics and data
science for human neuroscience research, preparing her for a successful career as an independent scholar.
Terms: <Accident and Emergency department><Acquired brain injury><Acute><Address><Affect><American><Animals><Antiinflammatory Effect><Aquadiol><Armed Forces Personnel><Astrocytes><Astrocytus><Astroglia><Astroprotein><Attention><Automobile collision><Automobile crash><Award><Axon><Biometrics><Biometry><Biostatistics><Blood Sample><Blood specimen><Brain><Brain Concussion><Brain Injuries><Brain Nervous System><Brain Trauma><Car collision><Car crash><Cephalalgia><Cephalgia><Cephalodynia><Cerebral Concussion><Chronic Post Traumatic Stress Disorder><Chronic stress><Commotio Cerebri><Complex><Congresses><Consensus><Cranial Pain><Craniocerebral Injuries><Craniocerebral Trauma><DSM-5><DSM-V><DSM5><DWI (diffusion weighted imaging)><DWI-MRI><Data><Data Reporting><Data Science><Data Set><Diagnosis><Diagnostic Findings><Diagnostic and Statistical Manual of Mental Disorders, 5th edition><Diagnostic and Statistical Manual of Mental Disorders-V><Differences between sexes><Differs between sexes><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Dimenformon><Dimensions><Diogyn><Diogynets><Discipline><Dysfunction><Emergency Department><Emergency room><Emotional Depression><Encephalon><Endocrine Gland Secretion><Estrace><Estradiol><Estradiol-17 beta><Estradiol-17beta><Estraldine><Exhibits><Extinction><Fear><Female><Fibroblast Intermediate Filament Proteins><Fright><Functional MRI><Functional Magnetic Resonance Imaging><Functional disorder><GFA-Protein><GFAP><Glial Fibrillary Acid Protein><Glial Fibrillary Acidic Protein><Glial Intermediate Filament Protein><Goals><Head><Head Injuries><Head Pain><Head Trauma><Headache><Health Surveys><Hormonal><Hormones><Hour><Human><Impairment><Individual><Injury><Intermediate Filament Proteins><Intervention><Intervention Strategies><Investigation><Investigators><Knowledge><Life><Light><Literature><Longitudinal Studies><MTBI><Masks><Measures><Mechanics><Mediating><Mediator><Menstrual cycle><Mental Depression><Mental Health><Mental Hygiene><Mentors><Military><Military Personnel><Modern Man><Motor vehicle collision><Motor vehicle crash><Neurobiology><Neuroendocrinology><Neurosciences Research><Outcome><Ovocyclin><Ovocylin><PTSD><Participant><Patient Recruitments><Patient Self-Report><Patients><Patients with traumatic brain injury><Perimenopausal><Perimenopause><Persons><Photoradiation><Physiatrics><Physiatry><Physical Medicine><Physiopathology><Population><Post-Traumatic Neuroses><Post-Traumatic Stress Disorders><Posttraumatic Neuroses><Predisposition><Prevalence><Progynon><Psychological Health><Psychopathology><QOL><Qualifying><Quality of life><Questionnaires><Rehabilitation Medicine><Reporting><Research><Research Personnel><Researchers><Rest><Risk><Risk Factors><Role><Sampling><Self-Report><Sex Differences><Sexual differences><Signs and Symptoms><Site><Sports><Stress><Susceptibility><Symptom Burden><Symptoms><TBI Patients><Therapeutic Estradiol><Therapeutic Hormone><Time><Training><Trauma><Traumatic Brain Injury><United States><Vehicle crash><Vehicular collision><Vehicular crash><Visual><Woman><abnormal psychology><acute stress><anti-inflammatory effect><assaulted sexually><associated symptom><astrocytic glia><biological adaptation to stress><brain damage><brain-injured><career><chronic PTSD><co-morbid symptom><co-occuring symptom><cohort><comorbid symptom><concurrent symptom><concussion><concussive><cooccuring symptom><dMRI><data representation><data representations><decrease resilience><decrease resiliency><depression><depression symptom><depressive><depressive symptoms><diffusion tensor imaging><disparity in health><experience><exposure to trauma><fMRI><falls><female outcomes><female sex hormone><head ache><health disparity><health related quality of life><injuries><interventional strategy><intimate partner violence><long-term study><longitudinal outcome studies><longterm study><lower resilience><lower resiliency><male><mechanic><mechanical><medical attention><member><men><menopause transition><mental state><mental status><mild TBI><mild brain trauma><mild traumatic brain injury><military population><neural circuit><neural circuitry><neural correlate><neural imaging><neuro-imaging><neuroactive steroids><neurobiological><neurocircuitry><neuroimaging><neuroimaging biomarker><neuroimaging marker><neurological imaging><neuroprotection><neuroprotective><neuropsychiatric><neuropsychiatry><neurosteroids><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><outcomes among females><outcomes among women><outcomes in females><outcomes in women><participant recruitment><pathophysiology><peri-menopausal><peri-menopause><physical assault><physical attack><post-doctoral training><post-trauma><post-trauma stress disorder><postdoctoral training><posttrauma><posttrauma stress disorder><pre-clinical research><preclinical research><psychosocial stresses><psychosocial stressors><reaction; crisis><recruit><reproductive><response><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><sexual assault><sexual attack><social role><stress response><stress; reaction><substantia alba><symptom association><symptom comorbidity><synaptic circuit><synaptic circuitry><tool><traffic collision><traffic crash><transition to menopause><transitional menopause><trauma exposure><traumatic brain damage><traumatic brain injury patients><traumatic event><traumatic neurosis><violence against women><white matter><women's outcomes>