Childhood Adversity May Trigger Elevated Stress Response in Healthy Adults

Deborah Brauser

October 15, 2010

October 15, 2010 — Healthy adults who are mistreated as children may have a higher inflammatory response to new stressors, new research suggests.

A pilot study conducted by researchers from Brown University and Butler Hospital in Providence, Rhode Island, shows elevated concentrations of the cytokine interleukin 6 (IL-6) in individuals who experienced early-life adversity.

"Past animal studies have given signals about how the functioning of an organism's stress response system can run amok for the rest of its life as a result of some of the earliest environment exposures," lead study author Linda L. Carpenter, MD, associate professor of psychiatry and human behavior at the Alpert Medical School at Brown and chief of the Mood Disorders Program at Butler, told Medscape Medical News.

"This is one of several studies we've been doing with generally healthy adults, looking at the effects of adverse early environment and how it can impact the brain and impact the eventual vulnerability for problems such as depression and anxiety," added Dr. Carpenter.

The investigators note, however, that "the mechanisms by which psychosocial stress initiates cytokine response," as well as the clinical consequences of this exaggerated response, still need to be determined.

"We're not yet at a point where we can tell healthy patients to get a stress-test cytokine profile done. But what's clear is that a life of excessive stress-induced inflammatory chemicals in the bloodstream is not good," said Dr. Carpenter. "So I think it's important for clinicians to help patients find ways to deal with this, such as with stress management."

The study was published online September 29 in Neuropsychopharmacology.

Detecting Biological Risk Markers

"A growing body of research has established that proinflammatory cytokines, such as [IL-6], have systemic effects far beyond the canonical immune response," investigators write.

They add that these immunomodulators have also been implicated in a number of psychiatric illnesses.

In a previous study, Dr. Carpenter and colleagues found a diminished cortisol response to stress in healthy adults who were exposed to childhood adversity. For this study, they sought to assess the IL-6 response to stress in a subset of patients from the earlier trial.

A cohort of 69 adults between the ages of 18 and 64 years (61% female) were given physical and neurologic examinations, as well as standard laboratory tests.

"Exclusion criteria included major medical illness, or use of any psychotropic medication or other drug thought to influence hypothalamic-pituitary-adrenal (HPA) axis function," the researchers write.

Patients were also excluded if they had a primary psychotic disorder or bipolar disorder, current substance dependence or abuse, current major mood or anxiety disorder, or prominent personality disorder.

All participants completed several surveys, including the Childhood Trauma Questionnaires (CTQ), about their childhood experiences.

On the basis of their self-ratings on the CTQ, 19 patients reported experiencing moderate to severe childhood maltreatment (MAL; 74% female; mean age, 32.84 years) compared with 50 who reported minimal or no maltreatment (healthy controls; 56% female; mean age, 24.5 years).

Serial plasma IL-6 concentrations were then measured in all participants during and after the Trier Social Stress Test (TSST), a standardized psychosocial role-play stressor.

Development Mediator Found

Results showed that total CQT scores "were positively correlated with overall change in IL-6 response" (P = .006), as well as with the maximum IL-6 concentration during the TSST (P = .002).

"Greater acute IL-6 release and higher IL-6 concentrations over time" were also observed for those in the MAL group compared with the healthy controls.

"The measured inflammatory protein was much higher when they started to stress and then got quite large after completing the stress test," said Dr. Carpenter.

She noted that the TSST was "just a small psychological stressor," such as something someone might feel when going to a job interview. "So seeing the significant amount of the body's response in those who had reported childhood maltreatment was really quite surprising, especially because these adults were really healthy."

Overall, "inflammation may be an important development mediator linking adverse experiences in early life to poor adult physical and mental health," write the researchers.

Dr. Carpenter said that this study shows the importance of asking patients about their early-life environment in terms of whether it was supportive or stressful or whether there were significant events, such as loss of a parent, abuse, or neglect.

"That might give a clue to some of the underlying biology that is relevant for whatever disorder you're treating, including migraine headache or a psychiatric disorder or a pain syndrome," she explained.

Dr. Carpenter reported that the National Institutes of Health has provided additional funding to allow her team to continue following up the patients from the overall study. "This will help us to understand various biological markers, including specific genes and some inflammatory markers, to see if there are types of relationships between these information states and the development of psychiatric disorders.

"We're going to be learning more and more about how immune system function and inflammation play a role in psychiatric health," concluded Dr. Carpenter. "I think the next 5 years are going to be really exciting in terms of understanding disorders such as depression from a new biological angle."

This study was funded by a grant from the National Institutes of Health. The study authors report several financial disclosures. A full list is published in the original article.

Neuropsychopharmacology. Published online September 29, 2010.


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