While PTSD Research Has Accelerated, Much About the Disorder Remains a Mystery

by U.S. Medicine

August 1, 2011

SAN FRANCISCO — Research into PTSD has accelerated exponentially over the last decade. Where once it was understood as little more than a loose collection of symptoms, now researchers are beginning to define the pathology of the disease as well as what effects it might have on other bodily systems. And, as patients with PTSD age, more is being understood about how PTSD will affect health the rest of their lives.

A number of studies have recently revealed that those diagnosed with PTSD are more likely to suffer from physical ailments as they grow older, including cardiovascular disease, stroke and dementia. Thanks to continuing work being done by VA researchers, including those at the San Francisco VA Medical Center, the reasons for the link between PTSD and those ailments is a mystery that soon could be solved.

What is still lacking, and a niche that researchers in San Francisco hope to fill, is in-depth research into different types of treatment that proves with scientific certainty which is more effective at treating PTSD.

Aging PTSD

The SFVAMC has a team of more than 20 investigators being funded by VA, DoD and NIH to do research into different facets of PTSD — psychiatrists, psychologists, internal medicine specialists, radiologists, laboratory medicine specialists and even a neurochemist and a biomedical engineer. All of them serve as principal investigators on a large portfolio of PTSD-related projects.

Much of that work focuses on aging veterans with PTSD and what the disease means for them as they grow older.

“We’re generally interested in the health effects of having PTSD, with a focus on the aging veteran,” said Thomas Neylan, MD, director of the PTSD program at SFVAMC. “As far back as 2009, we discovered that veterans with PTSD carry twice the risk of developing dementia later in life. We are keenly interested in what [other effects PTSD might have].”

That dementia discovery was made by Kristine Yaffe, MD, chief of geriatric psychiatry at SFVAMC. She and her team studied the records of 180,000 VA patients, most of whom were Vietnam or Korea-era veterans and found that patients with PTSD had a dementia rate of 10.6% compared to 6.6% for those without PTSD.

That finding pushed SFVAMC researchers to look for links between PTSD and brain functions. Brain imaging studies on PTSD patients done there and elsewhere in VA showed abnormalities in the hippocampus. “In particular, we found that PTSD is associated with a reduced volume in a region of the hippocampus that is associated with new neuronal growth in adults. That was the area that really seemed to be affected by PTSD,” Neylan said.

This reduced volume was found to also be associated with a decrease in sleep quality — a common symptom of PTSD. “This brings up the idea that sleep has a trophic or protective effect on the brain,” Neylan said.

While PTSD Research Has Accelerated, Much About the Disorder Remains a Mystery Cont.

Testing Treatments

How the disease impacts patients over time remains relatively unknown. Little has been done in the way of longitudinal imaging studies in PTSD patients. One study in 2003 showed patients treated with peroxetine — commonly used to treat depression and anxiety disorders — showed an increase in hippocampus size. Beyond that, little is known about how PTSD treatment counteracts the physical effects of the disease.

SFVAMC researchers are undertaking imaging studies on patients who have recovered from PTSD. Results have shown that people who have a past history of PTSD, but who currently do not suffer from it, have a hippocampus that looks totally normal.

“But we don’t know if, as their symptoms improve, their hippocampus expands in size or if a small hippocampus is a risk factor for PTSD,” Neylan said.

SFVAMC is moving toward a longitudinal study looking at different forms of treatment and imaging patients’ brains as they undergo the treatment process.

“Ultimately, we want to treat people and help them feel better,” Neylan said. “VA has two types of treatments for PTSD. One is prolonged exposure therapy, and the other is cognitive-processing therapy. The reality is that we are woefully lacking more comprehensive treatment studies on medications, psychotherapies, adjunctive treatments and alternative medicines. We really need a much better repertoire of treatments to offer veterans. That’s a glaring gap that we need to work on.”

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While PTSD Research Has Accelerated, Much About the Disorder Remains a Mystery Cont.

Imaging the Effects of PTSD

 “We’re looking ahead to try to understand why exactly it is that people with PTSD have a higher risk of dementia,” Neylan said. “One reason is that it might be related to increased risk of cerebral vascular disease, or it might be related to an Alzheimer’s-like pathology, which involves increased deposition of amyloid.”

The SFVAMC is currently working with DoD to create a study looking at TBI and at amyloid depositions in the brain, as well as doing lumbar punctures to look for tau protein — another marker for dementia. They will also be using MRI to detect cerebral vascular disease.

“This will allow investigators to separate the effects of vascular disease and amyloid, and also determine if there are interactions between these two processes,” explained Mike Weiner, MD, head of SFVAMC’s Center for Imaging of Neurodegenerative Disease.

This kind of study would not have been possible even a few years ago. A PET ligand to help image amyloid has been available for years, but the development of newer ligands — a molecule that binds to specific other molecules — has made it feasible to run studies in a larger number of centers. Also, the magnets used in MRI scans have grown more powerful.

“We’ve been lucky to have some of the best technology in that field. We have a four-Tesla magnet and will be receive a 7-Tesla magnet in the next year,” Neylan said. “Higher field-strength magnets produce better special resolution for structural imaging and more fine-grained analysis of white-matter tracts. Now we’re able to look at brain profusion in a way that you used to only be able to do using PET scans.”

“It’s all very preliminary, but now able to see things that we haven’t been able to see before,” Neylan said. “And we’re still trying to make sense of what we’re seeing.”

There is still room for improvement. Researchers would prefer to image tau protein, Weiner said, rather than detect it through lumbar punctures. “We would also love to be able to image ‘neuronal density,’ since neurodegeneration itself is currently difficult to quantify in living subjects,” he said. 

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