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Dexamethasone suppression test can indicate suicide risk.

MIAMI -- A dexamethasone suppression test can identify patients at increased risk of suicide, according to a follow-up study presented at the annual conference of the American Association of Suicidology.

Researchers striving to identify an endocrine basis for suicide have demonstrated that hyperarousal of the hypothalamic-pituitary-adrenal (HPA) axis, as manifested by a nonsuppressing dexamethasone suppression test (DST), can be an indirect predictor of suicide risk.

The DST fell out of favor in the late 1980s, when the National Institutes of Health and the American Psychiatric Association both determined that it lacked the sensitivity to diagnose major depression, the purpose for which it was touted throughout the earlier years of that decade, Dr. John Michael Bostwick said.

In the last few years, however, researchers have begun to resurrect the old data sets to see if DST status identifies subpopulations at risk for suicide. The technology has also advanced, and now there is an oral swab DST, so a blood draw is not required, he explained.

"A positive DST at any point back then seems to indicate an increased suicide risk down the road, which has implications for clinicians in assessing risk and implications for the role of the HPA axis in suicidal states," said Dr. Bostwick of Mayo Medical School, Rochester, Minn.

Dr. Bostwick and his colleagues compared 56 DST suppressors with 58 nonsuppressors identified in the mid-1980s. Participants received 1 mg dexamethasone at 11 p.m. on day 1, followed by three measurements of serum cortisol on day 2, according to the standard DST protocol. Nonsuppressors had 5 [mu]/dL cortisol or more at any collection time.

The researchers looked at death records an average of more than 15 years later to determine the number of suicides in each group. In the suppressor group, 45 participants were alive and 11 were dead, including one suicide. In the nonsuppressor group, 40 were alive and 18 were dead, including six suicides. The difference in the number of suicides between the two groups was statistically significant.

"We replicated Coryell's findings. We are very happy about that," Dr. Bostwick said. Dr. William Coryell and his colleagues found that 7 of 32 DST nonsuppressors committed suicide during an average follow-up of 10 years (Am. J. Psychiatry. 138[8]:1120-21, 1981.

Both nature and nurture contribute to how a person responds to stress, Dr. Bostwick said. Some patients may have a genetic basis for lower cortical serotonin levels. Lower serotonin, particularly in the prefrontal cortex, is linked to disturbances in regulation of anxiety and aggression. There is also evidence that chronic HPA-axis overdrive changes the brain's ability to modulate stress states, and some people have a genetic predisposition to this hyperactivity, Dr. Bostwick said.

There is a "double whammy in some patients who have an interaction between constitutional vulnerability and significant life events. Dr. Bostwick said, "Early adverse life experiences, such as trauma or neglect, can reduce the ability to tolerate stress later in life. Stress can trigger overwhelming anxiety and suicidal behavior but not necessarily depression." People at increased risk of suicide demonstrate this HPA-axis hyperactivity, but it is not observed in all depressed states, he added.

The stress response is complex and orchestrated. Researchers are focusing on the hypothalamus because it releases more corticotropin-releasing factor when threatened, causing the HPA axis to rev up quickly under stress as part of the "fight or flight response," he explained.

Some people at increased suicide risk have more receptors for corticotropin-releasing factor along the HPA axis, causing it to rev up quickly under stress. In the context of too much stress and too much cortisol, particularly in younger people, a smaller hippocampus can result. "There is a lot of suggestion that nonsuppressors [of dexamethasone] have a hippocampus that is no longer working as effectively in finetuning the stress response and turning it off. There is something different about the brains of people who don't suppress" dexamethasone, Dr. Bostwick said.

In response to a meeting attendee's question, Dr. Bostwick said that when a depressed patient is a nonsuppressor, particular attention should be paid to the signs of agitation or anxiety. He would be more likely to consider prescribing a benzodiazepine along with an antidepressant. "If you have someone in crisis, you need to give them something to control their agitation," he said, adding that he would also closely monitor such patients and be quicker to hospitalize them.

BY DAMIAN McNAMARA

Miami Bureau
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Title Annotation:Community Psychiatry
Author:McNamara, Damian
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Sep 1, 2004
Words:733
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