Nov. 3, 2009 Individuals who experience both childhood adversity and traumatic events in adulthood appear more likely to develop post-traumatic stress disorder than those exposed to only one of these types of incidents, according to a report in the November issue of Archives of General Psychiatry, one of the JAMA/Archives journals. In addition, the risk was further increased in individuals with a certain genetic mutation.
Although 40 percent to 70 percent of Americans have experienced traumatic events, only about 8 percent develop PTSD during their lifetimes, according to background information in the article. PTSD is a complex anxiety disorder that involves re-experiencing, avoidance and increased arousal following exposure to a life-threatening event. "In addition to the obvious effect of environmental factors, PTSD has a heritable component," the authors write. Recent studies estimate that genetic factors account for approximately 30 percent of the difference in PTSD symptoms.
Pingxing Xie, B.S., of Yale University School of Medicine, New Haven, Conn., and VA Connecticut Healthcare Center, West Haven, and colleagues studied 1,252 individuals who had experienced childhood adversity (including abuse or neglect), adult trauma (such as combat, sexual assault or a natural disaster) or both. Participants age 17 to 79 (average age 38.9) were interviewed and assessed for a variety of psychiatric and substance use disorders. DNA was extracted and used to differentiate between versions of a particular polymorphism or gene mutation -- known as the 5-HTTLPR genotype -- previously found to be associated with emotional response after stressful life events.
About one-fifth of the participants (229, or 18.3 percent) met criteria for PTSD. A total of 552 of the 1,252 participants (44.1 percent) experienced both childhood adversity and traumatic events in adulthood. These individuals were more likely to have a lifetime diagnosis of PTSD than were those who experienced trauma in only one life stage (29 percent vs. 9.9 percent).
"Although the 5-HTTLPR genotype alone did not predict the onset of PTSD, it interacted with adult traumatic events and childhood adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure," the authors write. The genotype may influence the way the brain processes the neurotransmitter serotonin, affecting an individual's anxiety levels and changing the way neurons react to fearful stimuli, they note.
"It was only in the group of subjects who could be characterized as having had the highest rates of trauma exposure (i.e., in both childhood and adulthood) that an impact of 5-HTTLPR could be detected," the authors conclude. "This suggests that there may be many neurobiological (including genetically determined) 'buffers' to PTSD; only in instances of extreme and/or repeated trauma exposure (which, it should be pointed out, characterizes those trauma 'types' with the highest conditional risk for PTSD, e.g., domestic violence and military combat), in which these buffers are overwhelmed, can the impact of specific genes such as 5-HTTLPR be detected."
This work was supported by National Institutes of Health grants.
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- Pingxing Xie; Henry R. Kranzler; James Poling; Murray B. Stein; Raymond F. Anton; Kathleen Brady; Roger D. Weiss; Lindsay Farrer; Joel Gelernter. Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations. Archives of General Psychiatry, 2009; 66 (11): 1201 DOI: 10.1001/archgenpsychiatry.2009.153
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