A recent study led by Shan Siddiqi, MD, from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, suggests that depression following traumatic brain injury (TBI) may represent a distinct clinical disorder rather than the conventional major depressive disorder. The implications of this research could have significant consequences for the treatment of patients. The findings have been published in Science Translational Medicine.

According to the corresponding author, Shan Siddiqi, MD, from the Brigham’s Department of Psychiatry and Center for Brain Circuit Therapeutics, their findings shed light on how physical trauma to specific brain circuits can lead to the development of depression. If their hypothesis is correct, it implies that depression after TBI should be managed as a separate disease. Many clinicians have long suspected that this condition possesses unique symptom patterns and treatment responses, including a limited response to conventional antidepressants, but until now, they lacked clear physiological evidence to support this notion.

The study involved collaboration with researchers from Washington University in St. Louis, Duke University School of Medicine, the University of Padua, and the Uniformed Services University of the Health Sciences. The research began as a side project seven years ago when Shan Siddiqi was motivated by a patient he shared with David Brody, MD, PhD, a co-author and a neurologist at the Uniformed Services University. They initiated a small clinical trial using personalized brain mapping to target brain stimulation as a treatment for TBI patients with depression. During this process, they observed specific abnormalities in the brain maps of these patients.

The study included 273 adults with TBI, primarily resulting from sports injuries, military incidents, or car accidents. This group was compared to other cohorts without TBI or depression, individuals with depression but without TBI, and people with posttraumatic stress disorder. Participants underwent resting-state functional connectivity MRI, a brain scan that observes oxygen movement in the brain. These scans provided oxygenation data at approximately 200,000 points in the brain and 1,000 different time points, generating about 200 million data points for each person. Machine learning algorithms were employed to create individualized brain maps based on this extensive information.

While the location of the brain circuit involved in depression was the same in both individuals with and without TBI, the nature of the abnormalities differed. In depression without TBI, connectivity in this circuit was reduced, whereas in TBI-associated depression, it was increased. This suggests that TBI-associated depression may involve a distinct disease process, leading the researchers to propose a new designation: “TBI affective syndrome.”

David Brody expressed that he has long suspected that this condition differs from typical major depressive disorder or other mental health conditions unrelated to traumatic brain injury. Although there is still much to comprehend, progress is being made in understanding the unique nature of this disorder.

One limitation of the trial was the sheer volume of data, which prevented the researchers from conducting detailed assessments of each patient beyond brain mapping. In the future, the investigators hope to use more sophisticated methods to assess participants’ behavior and potentially define various types of TBI-associated neuropsychiatric syndromes.

Shan Siddiqi and David Brody are using the insights gained from this study to develop personalized treatments. They initially designed a new treatment approach using brain mapping technology to target specific brain regions in TBI and depression patients, employing transcranial magnetic stimulation (TMS). A pilot trial with 15 participants showed promising results, and they have since received funding to replicate the study in a multicenter military trial.

The researchers aspire that their discovery will pave the way for a precision medicine approach to managing depression and mild TBI, and even enable intervention in neuro-vulnerable trauma survivors before the onset of chronic symptoms, as stated by Rajendra Morey, MD, a professor of psychiatry at Duke University School of Medicine and co-author of the study.


Source: Science Daily