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• Posted July 10, 2023

Depression That Hits After Brain Injury May Be Distinct Disease

Depression that arises after a head injury may be its own distinct condition -- one that differs from traditional major depressive disorder, a new study suggests.

Researchers found that people with post-concussion depression showed a unique pattern of activity in the brain circuitry involved in depression. This "picture" was different from depression unrelated to a head injury, and different from people who'd suffered a concussion but had no depression symptoms.

Experts said the findings shed light on the brain basis for post-concussion depression, and underscore an important take-away for patients: Your mental health symptoms are not just "in your head."

While most people recover from concussion, some have lingering symptoms, which can include depression. In fact, traumatic brain injury (which includes concussion) increases the risk of developing depression by about eightfold, studies show.

A key question has been whether that depression stems from the brain injury, per se, or from the emotional trauma of the incident that caused the injury -- whether a car accident, military combat or blow to the head on the football field.

Many experts have believed it's the brain injury, said Dr. Shan Siddiqi, the lead researcher on the new study and a clinical neuropsychiatrist at Brigham and Women's Hospital in Boston.

That's, in part, because the symptoms of post-concussion depression are often somewhat different, explained Siddiqi. People with major depression -- the "regular" depression that's commonly diagnosed -- typically have a hard time feeling pleasure.

That happens with post-concussion depression, too, Siddiqi said, but people also commonly show "excessive frustration." They may act impulsively or get angry over small matters, for example.

Beyond that, Siddiqi said, studies show that standard depression treatments -- antidepressants and talk therapy -- generally do not work as well for people with depression related to head injury.

Now the new findings, published recently in the journal Science Translational Medicine, point to brain-based differences.

"This type of depression does seem to be a unique disease related to the brain trauma people experienced," Siddiqi said.

The ultimate goal, he said, is to refine treatment for this form of depression. It remains to be proven, but he and his colleagues are studying whether transcranial magnetic stimulation (TMS) -- a non-invasive technique for stimulating nerve cells in the brain -- might be an effective approach.

The current study got its start when the researchers ran an early pilot trial of TMS. They targeted the stimulation to brain circuitry that, based on previous research, was hypothesized to be involved in the depression related to head injury.

The results were promising, but based on only a handful of patients. So the researchers needed more evidence they were targeting the right brain circuitry.

For the new study, they analyzed data on 273 adults who'd been part of other research projects where they'd undergone resting-state functional MRI. That's a type of brain imaging that tracks the flow of oxygen in the brain.

The group included people who'd suffered a traumatic brain injury (TBI) and developed depression; others with a recent TBI and no depression symptoms; people with depression but no TBI; and healthy individuals.

TBI refers to injuries caused by a blow to the head, with concussion on the milder end of the spectrum -- though they do cause significant problems for some people. Most study participants with TBI had suffered a concussion, Siddiqi said.

Overall, the researchers found, people with depression -- head injury or not -- showed abnormal "connectivity" within the same brain network. But the nature of the issue was different: Activity in those brain circuits was reduced in people with typical depression, but increased in those with depression after head injury.

Why is unclear, Siddiqi said. It's possible that for people with TBI-related depression, the head trauma damaged this particular brain circuitry. Or maybe the culprit is something that happens during the head injury healing process.

Right now, post-TBI depression is typically treated with the same medications developed for people with a "primary psychiatric diagnosis" -- not head trauma, said Dr. Lindsey Gurin, a specialist in TBI care who was not involved in the study.

She agreed the findings support the belief that the brain injury, itself, is a major part of the story in post-TBI depression.

TBI, in simple terms, "shakes up your whole brain," said Gurin, a clinical assistant professor of neurology, psychiatry and rehabilitative medicine at NYU Langone Health in New York City.

"What we see is that these patients can have problems with things like attention, concentration and regulation of emotional responses," Gurin said.

Yet when it comes to depression, she noted, some patients have guilt, or a feeling they should be able to "get over it."

"But this is a physiological problem," Gurin said, and needs to be addressed as such.

According to the U.S. Centers for Disease Control and Prevention, more than 223,000 Americans were hospitalized for TBI in 2019, and many more had head injuries that did not land them in the hospital. That same year, 15% of high school students said they'd suffered a sports- or recreation-related concussion in the past year.

More information

The U.S. Centers for Disease Control and Prevention has more on traumatic brain injury.

SOURCES: Shan Siddiqi, MD, assistant professor, psychiatry, Harvard Medical School, and clinical neuropsychiatrist, Brigham and Women's Hospital, Boston; Lindsey Gurin, MD, clinical assistant professor, neurology, psychiatry, and rehabilitation medicine, NYU Langone Health, New York City; Science Translational Medicine, July 5, 2023, online