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Depression After a TBI May Be a Distinct Condition

Cars speeding at sunset.
Patients who had TBIs as the result of a car accident were recruited for the study. Credit: Greg Rosenke/Unsplash

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A new study suggests that depression developing in the aftermath of a traumatic brain injury (TBI) should be characterized differently from classical major depressive disorder (MDD). The research analyzed brain patterns of depressed people who had experienced a TBI and identified unique patterns of activity among depression-related circuits in their brains, which separated them from people with depression who hadn’t had a TBI.

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The authors have published their findings in Science Translational Medicine.

Personalized brain map

The study was led by Dr. Shan Siddiqi, a psychiatrist at Brigham and Women’s Hospital. Siddiqi, who published the work alongside a multi-institution team, started the study seven years ago, when he began a small clinical trial alongside colleague Dr. David Brody. This trial was studying patients who had TBI and depression. Siddiqi and Brody developed a brain stimulation tool that they wanted to use to treat the patients, but had to develop a personalized brain map for each patient in order to know where to target the stimulation. While developing these maps, the duo noted that these patients’ brain maps had several distinctive features.

Our findings help explain how the physical trauma to specific brain circuits can lead to development of depression. If we’re right, it means that we should be treating depression after TBI like a distinct disease. Many clinicians have suspected that this is a clinically distinct disorder with a unique pattern of symptoms and unique treatment response, including poor response to conventional antidepressants – but until now, we didn’t have clear physiological evidence to prove this,” said Siddiqi.

The authors recruited 273 adult participants for the current study, a group that included those with TBI resulting from military service, sporting mishaps and vehicular accidents. These individuals were compared to groups without TBI or depression, those with depression but no TBI, and those with posttraumatic stress disorder.

200 million data points per person

Siddiqi and colleagues studied their participants’ brains using resting-state functional connectivity MRI, which looks at how oxygen-rich blood moves around the brain and is a proxy measure for brain circuit activation. This information allowed the team to measure oxygenation levels in up to 200,000 different points in the brain over 1,000 different timepoints. The resulting dataset, which consisted of roughly 200 million points of data per person, allowed the team to build a personalized brain map for each of their volunteers.

Interestingly, the researchers discovered the brain circuit involved in depression was located in the same brain region among TBI- affected and non-TBI-affected individuals. However, the nature of the abnormalities differed; connectivity in this circuit was reduced in non-TBI related depression but elevated in TBI-associated depression. This is early data, and only provides a snapshot of what is going on in the participants’ brains, but Siddiqi and colleagues suggest it could hint at the involvement of a different disease process, leading them to dub the TBI-related disorder “TBI affective syndrome.”

“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,” said Brody. “There's still a lot we don't understand, but we're starting to make progress.”


There are important limits to the findings. The team were unable to conduct more detailed assessments of their participants beyond their brain maps, meaning that many other variables that could potentially affect disease presentation and course were beyond the scope of the study. One limitation of the study was the inability to conduct detailed assessments of each participant beyond brain mapping, due to the volume of data. The research team aims to enhance future investigations with more sophisticated behavior assessments, which could delineate other types of TBI-associated neuropsychiatric syndromes.

The researchers want to use these maps practically, too. They have expanded on their original goal to identify brain circuits that could be targeted with a brain stimulation technique called transcranial magnetic stimulation (TMS). A pilot study of 15 volunteers produced promising results, say the team, who have now expanded to a larger, military-funded trial.

Dr. Rajendra Morey, a professor of psychiatry at Duke University School of Medicine, and co-author on the study, concluded, ““We hope our discovery guides a precision medicine approach to managing depression and mild TBI, and perhaps even intervene in neuro-vulnerable trauma survivors before the onset of chronic symptoms.”

Reference: Siddiqi SH, Kandala S, Hacker CD et al. Precision functional MRI mapping reveals distinct connectivity patterns for depression associated with traumatic brain injury. Sci Trans Med. 2023; 15: eabn0441. doi: 10.1126/scitranslmed.abn0441

This article is a rework of a press release issued by Brigham and Women's Hospital. Material has been edited for length and content.