illustrates head being hit by wrecking balls to show traumatic brain injury

Traumatic brain injury (TBI) can cause considerable physical, cognitive, and psychological damage, including personality changes, and in some cases, mental health disorders such as posttraumatic stress disorder (PTSD), and depression.

Traditional treatment for depression for a person with history of TBI is depression is similar to treatment for depression related to other types of trauma, stress, substance use, or other factors. But if research confirms the findings in a new study, that may change.

On July 5, 2023, the journal Science Translational Medicine published a study that employed extremely precise functional magnetic resonance imaging (fMRI) to document brain activity among people with depression. This study, led by Shan Siddiqi, MD, of Harvard University Medical School, suggests that TBI-related depression may be distinct from depressive disorders due to other causes.

Siddiqi and his team believe the differences are significant enough that depression caused by traumatic brain injury needs a new name: TBI affective syndrome.

What is a Traumatic Brain Injury?

The term traumatic brain injury refers to any change in brain functioning that results from some type of external force. According to the Brain Injury Association of America (BIAA), common causes of TBI include:

  • Motor vehicle accidents
  • Physical attacks
  • Intimate partner violence
  • Child abuse
  • Shaken baby syndrome
  • Gun violence
  • Slips and falls
  • Explosive devices
  • Injuries from sports or other recreational activities

Most people are surprised by the frequency of these types of injuries:

Healthcare professionals typically classify TBI as mild, moderate, or severe, based on the extent of the damage that a person incurs. However, it’s important to understand that mild in this context does not mean harmless. Concussions, which can result from an accidental or intentional blow to the head, usually receive a mild classification – but their effects can be significant and long-lasting.

Moderate and severe TBIs often result from physical assault (which can include child abuse), motor vehicle accidents, falls, explosions, and shootings.

Characteristics of Traumatic Brain Injury-Related Depression:

In an interview with STAT News, Siddiqi said that his team’s findings about TBI-related depression confirmed what many professionals suspect.

“As clinicians, a lot of us had a gut feeling that [TBI-associated depression] is a different disease,” Siddiqi told STAT News. “Why did nobody detect it before? I think the reason is because unlike other psychiatric disorders, TBI caused a sort of structural reorganization of the brain.”

One clue that TBI-related depression is different, Siddiqi said, appears in how people with various forms of depression respond to frustration:

  • Individuals with standard depressive disorders have difficulty experiencing pleasure, and quickly abandon hobbies or other activities when they become frustrated.
  • People with TBI-related depression often respond to this frustration with anger and impulsivity. Yet they refuse to give up the hobby or other activity, which indicates they don’t learn from their frustration.

Siddiqi said this response could indicate that TBI impacts the long axons in the brain. Axons are thin, cable-like structures that carry impulses between neurons. The damage, Siddiqi hypothesized, may stretch from the orbitofrontal cortex, just above the eyes, to the limbic system, which includes the amygdala and the hippocampus, and extends into the center of the brain.

TBI Changes Brain Connectivity

Using fMRI to test this hypothesis, Siddiqi and his team found what they described in their study as “a distinct brain connectivity profile” in people with TBI-related depression. They noted this profile as distinct from the profile of people with major depressive disorder without a TBI, TBI without depression.

Siddiqi acknowledged the need for further research for the following reasons:

  • The sample size in his stud was relatively small
  • More data may identify a cause-effect relationship between TBI-related depression and this newly discovered brain connectivity profile
  • Additional data may confirm depression can result from the physical impact of TBI, instead of from only the emotional trauma related to the event

If this future research supports and expands upon the results of this initial study, considerable changes in treatment for a high-risk but currently underserved population may follow.

“People with a TBI are nearly eight times more likely to have depression than people without one,” Siddiqi said in a July 6, 2023, Geo News article. “They’re also less likely to receive any kind of treatment for depression.”

Treatment for Traumatic Brain Injury-Related Depression

In his interview with STAT News, Siddiqi referred to prior research that suggests current interventions may not be effective for people who develop depression in the aftermath of a traumatic brain injury.

The results of one research effort appeared in the Journal of Neurotrauma in December 2009. This review, led by Jesse Fann MD, MPH, of the University of Washington, involved an assessment of 27 previously published studies.

Fann’s team reported that only a few previous studies investigated the benefits of medication, and that none of these studies provided “definitive evidence of efficacy” for any types of medications.

For clinicians who use pharmacotherapy to treat people with traumatic brain injury-related depression, the review team advised the following.

Medication for TBI-Related Depression: What to Consider

  • Begin with low doses, increase slowly, and remain vigilant for signs of adverse effects.
  • Selective serotonin reuptake inhibitors (SSRIs) – especially sertraline – may be the most effective first-line medication option.
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs) “may be another reasonable option” for treating people with TBI-related depression.
  • Tricyclic antidepressants show evidence of reduced effectiveness and increased risk of adverse effects when used by people with TBI-related depression.
  • Most monoamine oxidase inhibitors (MAOIs) should not be used, as they pose a serious risk of side effects for members of this patient population.

Ultimately, though, the review team found little evidence to suggest that medication offers a likely path to recovery from people who develop depression after a traumatic brain injury.

“We cannot assume that standard antidepressant medications will have the same efficacy and tolerability in persons with TBI as in persons without neurologic insult,” they wrote.

New Information Requires New Research

Fann’s team also found little data to validate the effectiveness of various non-medical approaches, such as electroconvulsive therapy (ECT), cognitive behavioral therapy (CBT), and mindfulness meditation.

“From the studies reviewed, there is insufficient evidence to support practice recommendations regarding any of the psychotherapeutic or rehabilitation interventions for depression following TBI,” they wrote.

The review team emphasized that their research did not mean that none of the commonly employed depression interventions could benefit people who had depression as a result of a traumatic brain injury. Their findings, they clarified, simply indicated that prior studies found no conclusive evidence they could help people with TBI-related depression.

Fourteen years after Fann’s team published their findings, Siddiqi’s research may explain the reason traditional forms of treatment have little success treating patients with a history of TBI.

Though Fann was not a member of Siddiqi’s team, he told NBC News that advances in neuroimaging underscore the need to view TBI-related depression in a different light.

“We cannot think about depression following TBI in the same way as we think about depression in other populations,” Fann said.