A recent study conducted 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 be a distinct disorder rather than the conventional major depressive disorder. This has important implications for the treatment of patients. The findings of the study 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, “Our findings help to explain how physical trauma to specific brain circuits can lead to the development of depression. If our hypothesis is correct, it means that depression after TBI should be treated as a separate disease.” He further adds, “Many clinicians have suspected that this is a distinct disorder with unique symptoms and treatment response, including poor response to conventional antidepressants. However, until now, we lacked clear physiological evidence to support this.”

Siddiqi collaborated 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 for this study. The research began as a side project seven years ago when Siddiqi and David Brody, MD, PhD, a co-author and neurologist at the Uniformed Services University, shared a patient. They initiated a small clinical trial that utilized personalized brain mapping to target brain stimulation as a treatment for TBI patients with depression. During the trial, they observed a specific pattern of abnormalities in the brain maps of these patients.

The study included 273 adults with TBI, typically resulting from sports injuries, military injuries, or car accidents. This group was compared to other groups without TBI or depression, those with depression but without TBI, and individuals with posttraumatic stress disorder. The participants underwent a resting-state functional connectivity MRI, which examined the movement of oxygen in the brain. These scans provided information about oxygenation at approximately 200,000 points in the brain, recorded at around 1,000 different time points, resulting in approximately 200 million data points per person. Using this information, a machine learning algorithm generated personalized brain maps for each individual.

Although the brain circuit involved in depression was found in the same location for individuals with and without TBI, the nature of the abnormalities differed. Connectivity in this circuit was decreased in depression without TBI but increased in TBI-associated depression. This suggests that TBI-associated depression may involve a distinct disease process, leading the researchers to propose a new name: “TBI affective syndrome.”

David Brody expressed his thoughts on the matter, stating, “I’ve always suspected it isn’t the same as regular major depressive disorder or other mental health conditions that are not related to traumatic brain injury. There’s still a lot we don’t understand, but we’re starting to make progress.”

One limitation of the trial was that due to the extensive data collected, the researchers were unable to conduct detailed assessments of each patient beyond brain mapping. As a future step, the investigators aim to evaluate participants’ behavior in a more advanced manner and potentially define different types of TBI-associated neuropsychiatric syndromes.

Siddiqi and Brody are also utilizing this approach to develop personalized treatments. Initially, they set out to design a new treatment by using brain mapping technology to target a specific brain region in TBI patients with depression, employing transcranial magnetic stimulation (TMS). They conducted a successful pilot study with 15 participants and have since received funding to replicate the study in a multicenter military trial.

Rajendra Morey, MD, a professor of psychiatry at Duke University School of Medicine and co-author of the study, expressed the hope that their discovery will guide a precision medicine approach to managing depression and mild TBI. Furthermore, they aim to intervene in trauma survivors with neuro-vulnerability before the onset of chronic symptoms.


Source: Science Daily