Browsing by Author "Tripodis, Yorghos"

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    National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome
    (Wolters Kluwer, 2021) Katz, Douglas I.; Bernick, Charles; Dodick, David W.; Mez, Jesse; Mariani, Megan L.; Adler, Charles H.; Alosco, Michael L.; Balcer, Laura J.; Banks, Sarah J.; Barr, William B.; Brody, David L.; Cantu, Robert C.; Dams-O’Connor, Kristen; Geda, Yonas E.; Jordan, Barry D.; McAllister, Thomas W.; Peskind, Elaine R.; Petersen, Ronald C.; Wethe, Jennifer V.; Zafonte, Ross D.; Foley, Éimear M.; Babcock, Debra J.; Koroshetz, Walter J.; Tripodis, Yorghos; McKee, Ann C.; Shenton, Martha E.; Cummings, Jeffrey L.; Reiman, Eric M.; Stern, Robert A.; Psychiatry, School of Medicine
    Objective: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298). Results: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features. Conclusions: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
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    White Matter Microstructure Is Associated with Serum Neuroactive Steroids and Psychological Functioning
    (Mary Ann Liebert, 2023) Umminger, Lisa F.; Rojczyk, Philine; Seitz-Holland, Johanna; Sollmann, Nico; Kaufmann, Elisabeth; Kinzel, Philipp; Zhang, Fan; Kochsiek, Janna; Langhein, Mina; Kim, Cara L.; Wiegand, Tim L. T.; Kilts, Jason D.; Naylor, Jennifer C.; Grant, Gerald A.; Rathi, Yogesh; Coleman, Michael J.; Bouix, Sylvain; Tripodis, Yorghos; Pasternak, Ofer; George, Mark S.; McAllister, Thomas W.; Zafonte, Ross; Stein, Murray B.; O'Donnell, Lauren J.; Marx, Christine E.; Shenton, Martha E.; Koerte, Inga K.; Psychiatry, School of Medicine
    Military service members are at increased risk for mental health issues, and comorbidity with mild traumatic brain injury (mTBI) is common. Largely overlapping symptoms between conditions suggest a shared pathophysiology. The present work investigates the associations among white matter microstructure, psychological functioning, and serum neuroactive steroids that are part of the stress-response system. Diffusion-weighted brain imaging was acquired from 163 participants (with and without military affiliation) and free-water-corrected fractional anisotropy (FAT) was extracted. Associations between serum neurosteroid levels of allopregnanolone (ALLO) and pregnenolone (PREGNE), psychological functioning, and whole-brain white matter microstructure were assessed using regression models. Moderation models tested the effect of mTBI and comorbid post-traumatic stress disorder (PTSD) and mTBI on these associations. ALLO is associated with whole-brain white matter FAT (β = 0.24, t = 3.05, p = 0.006). This association is significantly modulated by PTSD+mTBI comorbidity (β = 0.00, t = 2.50, p = 0.027), although an mTBI diagnosis alone did not significantly impact this association (p = 0.088). There was no significant association between PREGNE and FAT (p = 0.380). Importantly, lower FAT is associated with poor psychological functioning (β = -0.19, t = -2.35, p = 0.020). This study provides novel insight into a potential common pathophysiological mechanism of neurosteroid dysregulation underlying the high risk for mental health issues in military service members. Further, comorbidity of PTSD and mTBI may bring the compensatory effects of the brain's stress response to their limit. Future research is needed to investigate whether neurosteroid regulation may be a promising tool for restoring brain health and improving psychological functioning.