Sumantra Chattarji in his Bangalore lab
New Delhi, Sept. 11: In his Bangalore laboratory, biologist Sumantra Chattarji has spotted changes in brain cells that he believes can explain the mental trauma that haunts, among others, hundreds of US soldiers back home from Afghanistan and Iraq.
The brain cells have been extracted from rats that display behavioural changes that mimic a debilitating condition called post-traumatic stress disorder (PTSD) observed among survivors of combat, life-threatening situations and severe abuse.
Chattarji and his colleagues at the National Centre for Biological Sciences (NCBS), Bangalore, have detected subtle changes in cells of the amygdala, the brain’s hub of emotional memories, that they believe may explain the brain mechanisms underlying PTSD.
Their study also provides evidence to support a puzzling line of therapy in which cortisol, a stress hormone, is used to treat, or prevent, PTSD.
Their findings provide a new model for neuroscientists to fathom PTSD which, in India, has been observed among survivors of the 2004 tsunami, the 26/11 Mumbai attacks, and people who have experienced severe emotional trauma.
Patients with PTSD may experience bad dreams, frightening thoughts, or repeatedly recall the trauma they had faced weeks or months after the event. They may also suffer from depression, high anxiety levels or sleeping trouble.
The NCBS scientists have shown that a stress hormone given to rats in drinking water 12 hours before they are exposed to two-hour bouts of intense stress prevented PTSD-like delayed anxiety symptoms rather than exacerbated them.
“It’s a stunning result — this double whammy of stress seems good for the brain,” said Chattarji, a professor at the NCBS exploring the changes in the amygdala associated with mental stress. “The first dose of stress protects the brain from the second dose.”
The researchers designed two more experiments which also showed that rats with high levels of stress hormones were protected from PTSD-like symptoms. Their findings will be published this week in the journal Biological Psychiatry.
Their results are similar to those observed by psychiatrist Joseph Zohar at the Sheba Medical Centre and Tel Aviv University in Israel. In an earlier study, Zohar and his colleagues exposed two groups of rats to the smell of a cat and treated one group with cortisol after the exposure. Rats that received cortisol appeared less likely to be troubled after smelling the cat than rats that didn't get the cortisol.
Seven years ago, Chattarji’s team found that rats restrained from movement for two hours developed delayed anxiety and other behavioural changes that resembled those in patients with PTSD. The behavioural changes in the rats were also accompanied by a subtle yet significant increase in the number of the synapses, or connections, between cells in the amygdala.
In the new study, the researchers observed that every manipulation of the stress hormone that prevented the PTSD-like symptoms in the rats also prevented stress-induced synaptic changes in the amygdala.
“This is an elegant and thorough study,” said Luke Johnson, an assistant professor of neuroscience and psychiatry at the Uniformed Services University School of Medicine, Bethesda, Maryland, in the US, who was not connected with the study but is himself exploring the neurobiology of fear.
“The NCBS study provides a model for the hypothesis that the stress hormone is protective against acute stress,” Johnson told The Telegraph. But he cautioned that a limitation of the new research is that the observed changes in the amygdala have not yet been seen in human PTSD patients.
If future studies reveal the increase in synapses in the amygdala in PTSD patients, Johnson said, the NCBS study will turn out to be a “seminal study” in providing both the underlying and the treatment mechanisms to prevent the development of PTSD.
Psychiatrists say PTSD can be debilitating for patients. While there are no assessments of India’s burden of PTSD, a US study released four years ago by the RAND Corporation, a private think tank, had said that nearly 20 per cent of US military personnel who had returned from stints in Iraq or Afghanistan report symptoms of PTSD or major depression.
The NCBS findings have bolstered evidence for the use of cortisol for the treatment of PTSD, an idea first tested on patients by psychiatrists at the University of Zurich in Switzerland in 2004, but still under assessment through human clinical studies.
“This new study supports the idea that cortisol protects against PTSD if it is available in adequate amounts at the right time,” said Bruce McEwen, a neuroscientist at the Rockefeller University, New York, and a coauthor with the NCBS team. Over the past eight years, McEwen said, several studies have indicated that giving cortisol during or right after trauma will reduce the chances of people developing PTSD.
In one study described last year in the journal European Neuropsychopharmacology, Zohar and his colleagues offered trauma survivors entering a hospital cortisol or a placebo, a sham drug, and found that patients who received the cortisol were 60 per cent less likely to develop PTSD than the patients who received the placebo.
Chattarji, who worked with NCBS research scholars Rajnish Rao and Shobha Anilkumar, recalls that the study began with their chance discovery that some rats that received placebo injections of saline water appeared protected from delayed anxiety and the other PTSD-like symptoms.
“The joke in the lab was that we’d found the first animal model for the placebo effect,” said Chattarji. Some people respond to the placebo effect from the belief that they are receiving a real drug, but this is unknown in animals. “But I talked with Bruce (McEwen), and he suggested that what we were seeing might be the effect of the injection.”
The prick of the injection would stimulate the release of the stress hormone — a first dose of stress — which would prevent the animals from experiencing the delayed effects of the second dose of stress.
In their paper, Chattarji and his colleagues write that “the most striking” element of their findings is that two successive doses of stress reversed the growth of synapses within the amygdala to “unstressed... levels”. The results could, they hope, lead to new treatment strategies for trauma-associated disorders.