PTSD Linked to Smaller Cerebellum, Pointing to Potential New Target

A brain imaging study led by a team at Duke University has shown that adults with posttraumatic stress disorder (PTSD) have smaller cerebellums, suggesting that this part of the brain may represent a target for continued research into PTSD, and potentially the development of new therapeutic approaches.

“The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions,” said Ashley Huggins, PhD, who is first author of the team’s published study in Molecular Psychiatry, and who helped to carry out the work as a postdoctoral researcher at Duke in the lab of psychiatrist Raj Morey, MD.

The findings have prompted Huggins, who is now an assistant professor of psychology at the University of Arizona, to start looking for what comes first, a smaller cerebellum that might make people more susceptible to PTSD, or trauma-induced PTSD that leads to cerebellum shrinkage. Huggins also hopes the results will encourage others to consider the cerebellum as an important medical target for those with PTSD. “If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes.”

Huggins and colleagues for the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium (PGC) PTSD workgroup reported on their finding in a paper titled “Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMAPGC PTSD workgroup.” In their report the authors concluded, “Although the appreciation of the cerebellum for its contributions to cognitive and affective function is relatively recent, the current results bolster a growing literature confirming the cerebellum is not exclusively devoted to motor function and may, in fact, have unique relevance to psychiatric conditions including PTSD … The insights from the current study have revealed a novel treatment target that may be leveraged to improve treatment outcomes for PTSD.”

PTSD is a psychiatric disorder brought about by experiencing or witnessing a traumatic event, such as a car accident, sexual abuse, or military combat. Though most people who endure a traumatic experience are spared from the disorder, “… nearly 10% of trauma survivors develop chronic symptoms of posttraumatic stress disorder (PTSD), a debilitating psychiatric condition characterized by a constellation of symptoms including intrusive memories, avoidance, hypervigilance, and negative changes in mood and cognition,” the team explained.

Researchers have identified several brain regions involved in PTSD, including the almond-shaped amygdala that regulates fear, and the hippocampus, a critical hub for processing memories and routing them throughout the brain.

The grapefruit-sized cerebellum—the name is Latin for “little brain”—by contrast, has received less attention for its role in PTSD. “It’s a really complex area,” Huggins said. In fact, while the cerebellum makes up just 10% of the brain’s total volume but packs in more than half of the brain’s 86 billion nerve cells.

The cerebellum is best known for its role in coordinating balance and choreographing complex movements, like walking or dancing. But there is much more to it than that. The cerebellum can influence emotion and memory, which are impacted by PTSD. “If you look at how densely populated with neurons it is relative to the rest of the brain, it’s not that surprising that it does a lot more than balance and movement,” Huggins noted. The authors pointed out that the cerebellum shares connections with areas of the brain including the prefrontal and limbic areas, “strongly suggesting that it participates in processes beyond motor coordination that may be highly relevant of PTSD,” they noted. The cerebellum is also connected widely with stress-related regions of the brain, such as with the amygdala and hippocampus, which may make it especially vulnerable to traumatic stress, “… potentially leading to the development of PTSD symptoms by disrupting typical brain-mediated stress responses via cerebro-cerebellar circuits,” the team continued. But also, they added, “A growing body of structural and functional magnetic resonance imaging studies has begun to examine the role of the cerebellum in PTSD.”

Researchers have recently observed changes to the size of the tightly-packed cerebellum in PTSD. Most of that research, however, is limited by either a small dataset (fewer than 100 participants), broad anatomical boundaries, or a sole focus on certain patient populations, such as veterans or sexual assault victims with PTSD. And what isn’t known is whether a smaller cerebellum predisposes a person to PTSD or PTSD shrinks the brain region.

To help address these limitations in previous work Morey, along with over 40 other research groups that are part of the data-sharing consortium, pooled together their brain imaging scans to study PTSD as broadly and universally as possible.

They focused on images from 4,215 adult MRI scans, about a third of whom had been diagnosed with PTSD. And even with automated software to analyze the thousands of brain scans, Huggins manually spot-checked every image to make sure that the boundaries drawn around the cerebellum and its many subregions were accurate. “I spent a lot of time looking at cerebellums,” Huggins said.

The result of this thorough methodology was the consistent finding, that the cerebellums of PTSD patients were about two percent smaller than those of control individuals. And zooming in to specific areas within the cerebellum that influence emotion and memory, Huggins found similar cerebellar reductions in people with PTSD. “We found subregional specificity linking PTSD to smaller volumes in the posterior cerebellum, vermis, and flocculonodular cerebellum,” the team noted.

The results in addition indicated that the worse PTSD was for a person, the smaller was their cerebellum. “Focusing purely on a yes-or-no categorical diagnosis doesn’t always give us the clearest picture,” Huggins said. “When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume.”

Noting limitations of their study, the authors further concluded in their report, “Overall, these findings argue for a critical role of the cerebellum in the pathophysiology of PTSD, bolstering support for the region’s contributions to processes beyond vestibulomotor function.”

The researchers suggest the results are an important first step at looking at how and where PTSD affects the brain. There are more than 600,000 combinations of symptoms that can lead to a PTSD diagnosis, Huggins explained. Figuring out if different PTSD symptom combinations have different impacts on the brain will also be important to keep in mind.

For now, the researchers hope that their work will raise recognition of the cerebellum as an important driver of complex behavior and processes beyond gait and balance, as well as point to this brain region as a potential target for new and current treatments for people with PTSD. “The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function,” they wrote. “Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.”

Huggins added, “While there are good treatments that work for people with PTSD, we know they don’t work for everyone. If we can better understand what’s going on in the brain, then we can try to incorporate that information to come up with more effective treatments that are longer lasting and work for more people.” And as the authors pointed out, “Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.”