Post-traumatic Stress Disorder (PTSD) isn’t caused by just one faulty switch in the brain; it’s more like a tangled orchestra of genes and cells thrown off-key by trauma. With many genetic players involved, scientists are still piecing together the full score.
Now, researchers at Yale University are tuning in at the single-cell level, examining how the brain’s wiring might be misfiring in PTSD. By studying individual brain cells, they hope to catch where the communication goes awry and uncover how trauma changes the mind from the inside out.
In this first-of-its-kind study, researchers zoomed in on PTSD at the single-cell level to better understand how it affects the brain. Since there are no drugs made specifically for PTSD, doctors have long relied on antidepressants. But lead researcher Matthew Girgenti, hopes that by spotting unique molecular patterns linked to the disorder, scientists can create new treatments, or repurpose old ones.
In the new study, published in Nature, researchers analyzed over two million cell nuclei from the brain tissue of 111 people, focusing on a region called the dorsolateral prefrontal cortex, which is linked to decision-making and emotional control. They collected the samples post-mortem from individuals with, and without, PTSD and major depressive disorder.
They discovered that in the PTSD-affected brain, a special type of neuron – called inhibitory neurons – had genetic alterations. These neurons act like the brain’s volume knobs, helping to keep other neurons from overreacting.
But in PTSD and MDD (major depressive disorder), these knobs seem to be turned down, reducing neuronal communication. This could make the prefrontal cortex – responsible for emotional control and decision-making – get stuck in a hyperexcitable state, possibly leading to symptoms like nightmares and a heightened fight-or-flight response.
The team also noticed differences in microglia, the brain’s immune cells. These cells were a bit too chatty in brains with depression, but oddly quiet in PTSD, hinting at a key difference between the two conditions despite their many genetic overlaps.
And they didn’t stop there. The study also uncovered changes in the endothelial cells that line the brain’s blood vessels. Since these vessels carry stress hormones into the brain, the finding could help explain why people with PTSD often have elevated hormone levels, and how trauma ripples through the nervous system on a cellular level.
“We’ve already identified pathways – pathways refer to how genes talk to each other – that we think are targetable by particular drugs,” Girgenti said. “This was only made possible by looking at those individual cells and those individual molecular changes. Now we have to try and find drugs that will reverse that.”
Put simply, the findings paint a detailed picture of how trauma leaves lasting marks on the brain; right down to the cellular level. They reveal how specific cell types in the prefrontal cortex respond to stress at a molecular level, helping scientists understand how PTSD can reshape the brain’s function over time.
The study has been published in Nature.
Source: Yale School of Medicine
