Electroencephalographic Measures for the Diagnosis and Monitoring of Catatonia. - PROJECT SUMMARY Catatonia is a potentially fatal, often curable, and highly underdiagnosed neuropsychiatric disorder characterized by motor phenomena, changes in affect, and cognitive-behavioral disturbances. Once identified, catatonia can be rapidly and effectively treated, but in present clinical practice most cases of catatonia are not appropriately diagnosed. Thus, there is a critical unmet need to develop biomarkers to detect catatonia and to longitudinally monitor its treatment. This K23 Mentored Patient-Oriented Research Career Development Award will use detailed clinical phenotyping and machine learning analysis to transform clinical electroencephalography (EEG) recordings into valid, reliable, and accurate digital biomarkers for the detection and monitoring of catatonia. This will involve Aims of 1) developing a physiologic grading scale for catatonia using EEG recordings and contemporaneous clinical exam in the largest ever (N=1,400) prospective cohort of patients hospitalized with altered mental status; and 2) monitoring longitudinal EEG and clinical changes in patients with catatonia as they receive gold-standard treatment with benzodiazepines during the “lorazepam challenge test.” This research plan will be accompanied by a rigorous 5-year career development plan to advance the Principal Investigator, James Luccarelli, MD, DPhil, as a clinician-scientist with expertise in 1) prospective clinical research; 2) responsible conduct of research; 3); neurophysiology; 4) data science; and 5) scientific leadership and communication. This career development plan will build directly on Dr. Luccarelli’s clinical expertise in catatonia treatment for patients of all ages as a child, adolescent, and adult psychiatrist and his existing strengths in computational analysis and retrospective clinical research. On this foundation, training will be guided by a stellar team of mentors. Primary mentorship will be provided by Brandon Westover, MD, PhD, a neurologist and world leader in applying machine learning to human neurophysiology, along with co-mentor Timothy Wilens, MD, a child, adolescent, and adult psychiatrist and expert in prospective clinical research in psychiatric populations. Critical additional mentorship will be provided by cross-disciplinary team of scientific advisors: Paul Croarkin, DO (child psychiatry at the Mayo Clinic); Hang Lee, PhD (biostatistics); Sahar Zafar, MBBS (neurology); and Thomas McCoy, MD (bioethics). By leveraging the deep expertise of these world-class mentors and the unparalleled institutional environments of the Massachusetts General Hospital and Harvard Medical School, this K23 Award will support an innovative program of career development and patient-oriented research. This will provide Dr. Luccarelli with the skills necessary to become an independent investigator leveraging a clinically actionable biomarker for the enhanced clinical detection and monitoring of catatonia that will set the stage for future EEG-guided clinical trials of new treatments.
