In PTSD, Brain Overreacts to Cues Not Directly Linked to Negative Experiences

In PTSD, Brain Overreacts to Cues Not Directly Linked to Negative Experiences

Posted: February 5, 2016
TAKEAWAY: Researchers have identified a molecular pathway in a specific neural connection in the brain that is disrupted in patients with 22q11 deletion syndrome, a genetic error that is associated with schizophrenia. The pathway, which relies on a microRNA called miR-338-3p, is involved in neural communication between regions of the brain that are likely involved in auditory hallucinations and psychosis, suggesting it may be a potential drug target for alternative therapeutic strategies

In people with post-traumatic stress disorder (PTSD), fear-associated brain circuits overreact to cues that are similar to—but not the same as—features of a past traumatic experience. For example, the sound of a passing car’s  backfire might trigger a response in someone who has been traumatized by gun violence.  

A new study of fear responses in military veterans both with and without PTSD has identified regions of the brain involved in this generalization of fear. Further, the research suggests that in people who have PTSD, stimuli in the environment associated with intense emotion are most likely to elicit generalized fear, whether or not directly associated with the original, triggering traumatic event.

The study, published December 15 in the journal Translational Psychiatry, was led by 1998 and 2000 NARSAD Young Investigator grantee Kevin S. LaBar, Ph.D., at Duke University and first author Rajendra A. Morey of the same institution. According to the researchers, their findings suggest that people with PTSD may benefit from exposure therapy that calls for intentional exposure to triggers that are tangentially, rather than directly, related to a past trauma.

To compare how the neural circuitry that controls fear is altered by negative experience in people with and without PTSD, the scientists used functional MRI (magnetic resonance imaging) to monitor brain activity in 67 military veterans, 32 of whom had been diagnosed with PTSD. The other 35 participants had also been exposed to traumas, but had not developed PTSD.

The researchers monitored participants' brain activity while they were shown five pictures of the same face expressing different intensities of fear. Then, outside the MRI scanner, participants were shown the images several more times. When the face depicting moderate fear was presented, it was sometimes paired with a mild electric shock.  

Subjects then returned to the MRI scanner so the researchers could monitor their brain activity while they viewed the five faces again. This time, the scientists looked for any changes in the brain's response to the images compared to its response prior to the negative experience of the electric shock.

When participants saw the moderately fearful face that had been paired with the shock, several regions of the brain responded more vigorously than they had previously. But in people with PTSD, this heightened activity also occurred when the most fearful face in the series was presented—even though no shock or other negative experience had been paired with that face.

Participants with PTSD also had trouble remembering which face had been paired with the shock, frequently identifying the face expressing the greatest fear as the image associated with the negative experience. The results suggest that fear generalization in people with PTSD is biased toward stimuli with higher emotional intensity.

Read the paper.

TAKEAWAY: Researchers have identified a molecular pathway in a specific neural connection in the brain that is disrupted in patients with 22q11 deletion syndrome, a genetic error that is associated with schizophrenia. The pathway, which relies on a microRNA called miR-338-3p, is involved in neural communication between regions of the brain that are likely involved in auditory hallucinations and psychosis, suggesting it may be a potential drug target for alternative therapeutic strategies Friday, February 5, 2016

In people with post-traumatic stress disorder (PTSD), fear-associated brain circuits overreact to cues that are similar to—but not the same as—features of a past traumatic experience. For example, the sound of a passing car’s  backfire might trigger a response in someone who has been traumatized by gun violence.  

A new study of fear responses in military veterans both with and without PTSD has identified regions of the brain involved in this generalization of fear. Further, the research suggests that in people who have PTSD, stimuli in the environment associated with intense emotion are most likely to elicit generalized fear, whether or not directly associated with the original, triggering traumatic event.

The study, published December 15 in the journal Translational Psychiatry, was led by 1998 and 2000 NARSAD Young Investigator grantee Kevin S. LaBar, Ph.D., at Duke University and first author Rajendra A. Morey of the same institution. According to the researchers, their findings suggest that people with PTSD may benefit from exposure therapy that calls for intentional exposure to triggers that are tangentially, rather than directly, related to a past trauma.

To compare how the neural circuitry that controls fear is altered by negative experience in people with and without PTSD, the scientists used functional MRI (magnetic resonance imaging) to monitor brain activity in 67 military veterans, 32 of whom had been diagnosed with PTSD. The other 35 participants had also been exposed to traumas, but had not developed PTSD.

The researchers monitored participants' brain activity while they were shown five pictures of the same face expressing different intensities of fear. Then, outside the MRI scanner, participants were shown the images several more times. When the face depicting moderate fear was presented, it was sometimes paired with a mild electric shock.  

Subjects then returned to the MRI scanner so the researchers could monitor their brain activity while they viewed the five faces again. This time, the scientists looked for any changes in the brain's response to the images compared to its response prior to the negative experience of the electric shock.

When participants saw the moderately fearful face that had been paired with the shock, several regions of the brain responded more vigorously than they had previously. But in people with PTSD, this heightened activity also occurred when the most fearful face in the series was presented—even though no shock or other negative experience had been paired with that face.

Participants with PTSD also had trouble remembering which face had been paired with the shock, frequently identifying the face expressing the greatest fear as the image associated with the negative experience. The results suggest that fear generalization in people with PTSD is biased toward stimuli with higher emotional intensity.

Read the paper.