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The $8-million dollar DISENTANGLE initiative, led by Sam McLean, MD, MPH, at the UNC School of Medicine and funded through the U.S. Department of Defense, will leverage the latest data on brain injury biomarkers and clinical observations to prevent and treat severe posttraumatic symptoms.


CHAPEL HILL, NC – Civilians and military personnel commonly experience traumatic events that often involve traumatic brain injury (TBI) and tremendous stress, leading to acute and chronic “posttraumatic” symptoms, such as depression, severe anxiety, pain, and many others. But researchers still lack a sufficient understanding for how TBI and profound stress – and their combination – lead to a wide variety of health outcomes. This lack of understanding is a major barrier to developing more effective prevention measures and treatment interventions.

Led By Sam McLean, MD, MPH, director of the UNC Institute for Trauma Recovery, researchers have established an $8-million initiative funded through the U.S. Department of Defense to overcome this lack of understanding. It’s called DISENTANGLE – Discovering DIagnostics, SubtypEs, and NaTurAl history of traumatic brain iNjury vs. non-TBI Recovery to Gain MiLitary advantage.

“We are fortunate to have two new resources to bring to this problem in DISENTANGLE”, said McLean, professor of psychiatry in the UNC School of Medicine and principal investigator of the study. “The first is data from AURORA study researchers who have collected meticulous information on head trauma and stress exposure from thousands of individuals, who had come to emergency departments after motor vehicle collisions. The second resource is a new blood test that can more accurately identify brain injury.”

AURORA began in 2016 thanks to a $21-million grant from the National Institutes of Health to better understand, prevent, and treat adverse posttraumatic neurologic and mental health outcome. McLean and colleagues received further NIH and DOD funding, as well as millions of dollars from private organizations, including One Mind, a nonprofit dedicated to accelerating brain health research and advocacy. AURORA now totals $40 in funding.

Before AURORA, it had been difficult to understand how stress alone – or as a result of TBI –affects acute and chronic health outcomes. Researchers have traditionally used the presence of specific posttraumatic symptoms to identify individuals with TBI, but such symptoms have been observed in individuals without TBI. Compounding the problem, TBI researchers and non-TBI researchers studying health outcomes have tended to make different assumptions and collect different data, making it difficult to evaluate the effects of stress and TBI independently of each other and in combination.

This lack of understanding regarding how profound stress, TBI, and their combination shape acute and chronic health outcomes is major barrier to developing more effective preventive and treatment interventions.

DISENTANGLE researchers are confident they can gain new insights to help millions of people who suffer from posttraumatic stress and various health issues, especially veterans who experience trauma from combat.

Along with AURORA data and previous published studies, McLean and colleagues will use

Newly developed blood tests validated in the TRACK-TBI study by leading TBI researchers, including DISENTANGLE collaborator Geoffrey Manley, MD, PhD, chief of neurosurgery at Zuckerberg San Francisco General Hospital, professor and vice chair of neurological surgery at UCSF.

“By analyzing these blood-based biomarkers from the thousands of patients in AURORA,” Manley said, “we hope to better understand how profound stress, TBI, and their combination shape symptom course, neuroimaging characteristics, neurocognitive function, gene expression and other molecular characteristics, as well as wrist wearable and smartphone characteristics in the weeks and months after trauma.”

In addition to UNC and UCSF, the DISENTANGLE team includes investigators from several other universities, including Harvard University and Emory University. Key AURORA funding partner One Mind is excited to see mental health and TBI experts come together to advance this research.

“As a seminal funding partner and guide for both the AURORA and TRACK-TBI studies, we are ecstatic to see the Department of Defense step forward to help launch the $8 million DISENTANGLE initiative,” said Brandon Staglin, One Mind’s President. “We look forward to their collaboration enhancing our understanding of how brain injury and emotional stress combine to influence posttraumatic outcomes.”

Media contact: Mark Derewicz, 919-923-0959