Credit: Pixabay/CC0 Public Domain
A new study
led by Shan Siddiqi, MD, from Brigham and Women's Hospital, a founding member
of the Mass General Brigham health care system, suggests that depression after
traumatic brain injury (TBI) could be a clinically distinct disorder rather
than traditional major depressive disorder, with implications for patient
treatment. The findings are published in Science
Translational Medicine.
"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," said corresponding author Shan Siddiqi, MD,
of the Brigham's Department of Psychiatry and Center for Brain Circuit
Therapeutics.
"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."
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 on the
study.
The work started as a side project seven years ago when Siddiqi was motivated by a patient he shared with David Brody, MD, Ph.D., a co-author on the study and a neurologist at Uniformed Services University. The two started a small clinical trial that used personalized brain mapping to target brain stimulation as a treatment for TBI patients with depression. In the process, they noticed a specific pattern of abnormalities in these patients' brain maps.
A unique brain network architecture in depression
after traumatic brain injury: the study and the story behind the science.
Credit: Shan H. Siddiqi
The current study included 273 adults with TBI, usually from sports
injuries, military injuries, or car accidents. People in this group were
compared to other groups who did not have a TBI or depression, people with
depression without TBI, and people with post-traumatic stress disorder.
Study participants went through a resting-state functional connectivity
MRI, a brain scan that looks at how oxygen is moving in the brain. These scans
gave information about oxygenation in up to 200,000 points in the brain at
about 1,000 different points in time, leading to about 200 million data points in each
person. Based on this information, a machine learning algorithm was used to
generate an individualized map of each person's brain.
The location of the brain circuit involved in depression was the same among
people with TBI as people without TBI, but the nature of the abnormalities was
different. Connectivity in this circuit was decreased in depression without TBI
and was increased in TBI-associated depression. This implies that
TBI-associated depression may be a different disease process, leading the study
authors to propose a new name: "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."
One limitation of the trial is that with so much data, the researchers were
not able to do detailed assessments of each patient beyond brain mapping. As a
future step, investigators would like to assess participants' behavior in a
more sophisticated way and potentially define different kinds of TBI-associated
neuropsychiatric syndromes.
Siddiqi and Brody are also using this approach to develop personalized
treatments. Originally, they set out to design a new treatment in which they
used this brain mapping technology to target a specific brain region for people with TBI
and depression, using transcranial magnetic stimulation (TMS). They enrolled 15
people in the pilot and saw success with the treatment. Since then, they have
received funding to replicate the study in a multi-center military trial.
"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," said Rajendra Morey, MD, a professor of psychiatry at Duke University School of Medicine, and co-author on the study.
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