DNA analysis gives clues to how the ancient hominin’s population split and how they interacted with modern humans.
Researchers working in war-torn countries find hints to the molecular roots of posttraumatic stress disorder.
August 1, 2012|
In February 2008, Thomas Elbert, a neuropsychologist at Germany’s Universität Konstanz, paid a visit to a man in northern Uganda who had been recruited as a child soldier shortly after the 1994 Rwandan genocide—a bloody ethnic conflict that claimed more than 500,000 lives according to conservative estimates. Elbert watched the man grab a cable lying on the floor, wrap it around his torso like an ammunition belt, wield a piece of scrap metal as if it were an AK-47, and command an empty room to prepare for an attack.
When the man finally emerged from his confused state, he had no understanding or memory of what had just happened. “This man experienced this four or five times a week,” Elbert says. And he’s just one of many.
This is the very first genetic link between emotional memory, traumatic memory, and posttraumatic stress disorder.
—Andreas Papassotiropoulos, University of Basel
For the past 3 decades, Elbert has traveled to some of the world’s deadliest war zones—including Somalia, eastern Congo, Sudan, Afghanistan, Iraq, and northeastern Sri Lanka—to treat people severely traumatized by warfare and violence. While his main goal is to alleviate their suffering, his work has afforded him a unique opportunity to understand the effects of traumatic stresses at a population level.
Like his contemporaries working in war-torn countries, Elbert has noted that children who have grown up in violent places have memory problems. Specifically, they are less able to temporarily store information that helps them stay focused, complete tasks, and comprehend concepts—a type of short-term memory psychologists call “working memory.” Their ability to contextualize memories to a specific time and place, called “episodic memory,” is also sometimes impaired.
“If your working memory is reduced, you’ll have difficulty having a cool response—in thinking it completely through—because you don’t understand what is really going on,” Elbert explains. “You’ll respond more with an angry outburst to a stressful situation. This is how humans adapt to a threatening and adverse environment.”
Elbert’s field observations are supported by research showing that traumatic experiences effect neuronal and epigenetic changes in the brain, particularly in regions such as the hippocampus and the amygdala. “After a high enough ‘load of traumatic stress,’ everybody will become mentally ill,” Elbert says. But it’s still very unclear why, when faced with fewer or less frequent traumatic experiences, some people develop severe anxiety disorders, such as posttraumatic stress disorder (PTSD), and others don’t, says Tobias Hecker, a clinical psychologist also at Universität Konstanz. For the past few years, Hecker has been helping with the reintegration of former child soldiers in the Democratic Republic of the Congo, where nearly 20 percent of the population suffers from PTSD, according to his research.
To better understand the development of PTSD, Andreas Papassotiropoulos, a molecular psychologist at the University of Basel in Switzerland, has been exploring yet another kind of memory—emotional memory—which deals with storing information of an emotionally evocative nature. Previous research showed that disturbed emotional memory can lead to certain psychiatric disorders and that people’s capacity for this type of memory varies. Papassotiropoulos believes that individuals with an enhanced capability for remembering intense emotional events may be at higher risk for developing PTSD.
“We know the neural pathways involved in emotional memory,” Papassotiropoulos says. “What is not known are the molecular underpinnings of this capacity.”
Recently, however, work in model organisms such as rats has hinted at the involvement of certain molecules, including kinases and phosphatases, in creating emotional memories. Kinases phosphorylate other molecules, which in turn activate transcription factors that turn on the expression of downstream genes. “These kinases are intimately involved in gene expression in certain nerve cells in the amygdala,” where emotional memories are processed, Papassotiropoulos explains.
In 2010, Papassotiropoulos and a team of psychologists, neuroscientists, and geneticists scanned for more than 2,000 single nucleotide polymorphisms (SNPs) in genes encoding protein kinases in a sample of 723 healthy young Swiss adults. The test subjects were also asked to perform memory tasks. The researchers zeroed in on a particular polymorphism—SNP rs4790904—located within the protein kinase C alpha (PKCa) coding region, which correlated with a varying capacity for remembering emotion-inducing things or events. When shown a wide variety of images, subjects homozygous for a specific variant of this polymorphism, dubbed the A allele, were better able to remembering negative or positive pictures than neutral pictures. The team then had a separate sample of 394 healthy Swiss young adults, typed for rs4790904 alleles, perform the same memory tests while undergoing functional magnetic resonance imaging (fMRI). Those homozygous for the A allele not only scored highest on emotional memory, they also showed enhanced brain activity in regions of the brain associated with emotional-memory performance. Subjects with only one copy of the A allele performed better in these memory tasks than subjects who didn’t have the variant at all, but not as well as A allele homozygotes.
In light of the findings, which were reported this spring in the Proceedings of the National Academy of Sciences, Papassotiropoulos teamed up with Elbert, who in 2003 had established an outpatient clinic in Uganda’s Nakivale refugee camp that subsequently became a center for treating survivors of the Rwandan genocide. Among the patients Elbert treated was a man who would have severe epileptic-like seizures at the mere mention of words such as “war” and “machete.”
Elbert collected saliva samples from 347 refugees, 134 of whom had been diagnosed with PTSD, and found that having the A allele of the SNP rs4790904 polymorphism was correlated with an increased risk of PTSD, as well as an enhanced ability to vividly remember and reexperience past traumatic events.
“This is the very first genetic link between emotional memory, traumatic memory, and posttraumatic stress disorder,” says Papassotiropoulos, adding that the polymorphism is likely a proxy for a yet-to-be identified mutation in the vicinity of the variant. The next step will be to probe the PKCa region for specific mutations that are causally associated with enhanced emotional memory.
“Only by knowing the underlying biology will we be able to identify drugs that alleviate PTSD,” Papassotiropoulos adds.