A team of biologists at Bangalore's National Centre for Biological Sciences claim to have identified intriguing new biochemical signatures in the brain suggesting how the effects of post-traumatic stress disorder (PTSD) can be countered, reports Kalyan Ray.
The victims of the 2004 tsunami had experienced it after they were shell-shocked by those monstrous waves that came ashore. Now a team of biologists in Bangalore claim to have identified intriguing new biochemical signatures in the brain suggesting how the effects of post-traumatic stress disorder (PTSD) can be countered.
The results are so counter-intuitive that the team at the National Centre for Biological Sciences (NCBS) refused to believe it first. Repeated experiments in the laboratory with rodents finally convinced them that their study has the potential to change the stress-management regimen in the clinical set up, in the long run.
The condition is a severe form of anxiety disorder witnessed by individuals exposed to natural calamities, wars, violence and emotional abuses. The victims not merely remember their trauma, but they re-live those events as flashback, nightmares and intrusive thoughts.
They feel numb and emotionally disconnected with their loved ones yet they remain tense, irritable and hyper-vigilant all the time as if the danger is lurking around the corner. The symptoms were first recognised among the survivors of Vietnam war but were seen later in those soldiers who returned from wars in Iraq and Afghanistan.
Closer home, PTSD is not seen much among Indian soldiers. "It's because India is a collective society and soldiers get support from their family. Post-traumatic stress disorder as a disease is very low in the Indian armed forces. But it is seem widely in individualistic societies to which soldiers fighting in Iraq, Afghanistan and Vietnam belong," said Manas Mandal, Director of Defence Institute of Psychological Research in Delhi.
The NCBS team has discovered that a particular stress hormone, whose levels increase in the body following any stress event, may reduce the development of PTSD.
"The results were so counter-intuitive that we did not believe it first. But there are medical records clearly showing PTSD patients getting benefited from rising level of a stress hormone named cortisol," NCBS scientist Sumantra Chattarji told Deccan Herald. The results are consistent with clinical reports on the protective effects of cortisol against the development of PTSD symptoms triggered by traumatic stress.
Placebo effect
The NCBS team got its lucky break while conducting experiments to test some other theory. Chattarji and his colleagues Rajnish Rao and Shobha Anil Kumar gave placebo injections to a group of rats, which acted as control in the experiment. To their surprise, they found that half of the anxiety effects in rats went away.
"The joke in the laboratory was that we have discovered the world's first animal model for placebo effect," Chattarji told Deccan Herald. Placebo effects are well-established in research.
They are seen when a person experiences the same benefits of a medicine even though the s/he did not actually consume the drug. It is a standard part of any drug trial in which a group of people is given a sugar pill (or saline water) devoid of the medicine but they are made to believe that they are consuming a real drug. The thought and belief in having a medicine triggers beneficial action in those individuals. These effects are not seen in animals.
Then the NCBS researchers discussed the surprising 'placebo effect' seen in rats with Bruce McEwen of Rokefeller University in New York who offered an explanation. The tiny prick that the rodents received caused pain in the animal as a result of which the cortisol level in the body shot up. The surge in stress hormone level protected the rats from anxiety disorders.
"We then planned a full-blown experiment. The rats were subjected to two levels of stress, they were given drinking water laced with cortisol for 12 hours. Then the animals were kept immobilised for two hours increasing their stress level enormously. But the effects were completely opposite to known theories. There were no traces of anxiety," he said.
Similar effects were seen in intensive care units in USA and Israel where cardiac surgery patients with PTSD displayed lesser influence of PTSD after cortisol treatment. This led to a medical hypothesis that inadequate cortisol could make patients vulnerable to PTSD.
"The work was inspired by this puzzle and counter intuitive clinical reports showing that individuals with lower levels of cortisol are more susceptible to developing PTSD and that cortisol treatment in turn reduces the cardinal symptoms of PTSD. Using a rodent model of acute stress, we were not only able to capture the essence of these clinical reports, but also identify a possible cellular mechanism in the amygdala, the emotional hub of the brain," Chattarji said. The research was published in the September 15 issue of Biological Psychiatry.
The stress hormone when given from outside, he said, prevented the formation of new synaptic connections in amygdala and thereby prevents developing anxiety disorders. As there is no new wiring (synaptic connections) of amygdala, there is no anxiety. Scientists claim high and low numbers of synapses in the amygdala appear to be reliable predictors of high and low anxiety states respectively.
"It seems, increasingly, that the 'trauma' in post traumatic stress disorder is the impact of stress on brain structure and function," commented John Krystal, editor of Biological Psychiatry and a professor at Yale School of Medicine. "The study provides evidence that glucocorticoids may have protective effects in their animal model that prevent from these changes in synaptic connectivity, potentially shedding light on protective effects of glucocorticoids described in relation to PTSD." Glucocorticoids is a group of stress hormones that includes cortisol.
Clinically significant
The study was clinically significant as it pointed out how the consequences of PTSD could be countered in the long run, Sanjeev Jain, professor of psychiatry at National Institute of Mental Health and Neurosciences in Bangalore told Deccan Herald. "With the increasing costs and suffering associated with PTSD victims, it is our hope that basic research of the kind reported in this study will help in developing new therapeutic strategies against this debilitating disorder. Given at right dose and right time, cortisol is not all bad," concluded Chattarji.