PET imaging finds suicidal ideation where its biomarkers are hiding in the brain

Positron emission tomography has proven capable of identifying serotonin binding patterns in the brain that correlate with suicidal ideation and, in some cases, precede lethal suicidal behavior, according to a study lead-authored by the president of the American Psychiatric Association and published online in JAMA Psychiatry.

Maria Oquendo, MD, of Columbia University and colleagues conducted a prospective, observational study that enrolled 100 patients, including 51 who had previously attempted suicide, who presented for treatment of a major depressive episode of at least moderate severity.

The patients underwent PET scans using [¹¹C]WAY-100635, a serotonin_1A antagonist. A subset of 50 patients additionally underwent imaging with [¹¹C]DASB, a serotonin transporter radioligand.

The imaging was performed at Columbia University Medical Center from 1999 to 2008.

The patients were “treated naturalistically in the community,” the authors report, “and followed up for two years with documentation of suicidal behavior, its lethality, and suicidal ideation and intent.”

Of the 100 patients undergoing follow-up evaluations (39 men and 61 women, mean age of 40.2 years), some 15 made suicide attempts.

Two of these patients died by suicide during the study’s two-year follow-up phase, which ended in May of 2010.

Analyzing the data from August 2013 until this past March, the researchers found that higher serotonin_1A binding potential in the raphe nuclei cluster of the brain stem predicted more suicidal ideation at three months (b = 0.02; t = 3.45) and one year (b = 0.02; t = 3.63), along with higher lethality of subsequent suicidal behavior (b = 0.08; t = 2.89).

The team’s exploratory analyses further suggested that the serotonin_1A binding potential of the insula, anterior cingulate and dorsolateral prefrontal cortex were similarly predictive of lethality.

Meanwhile, contrary to the researchers’ guiding hypotheses, suicidal intent was not predicted by serotonin_1A binding potential in any brain region, and midbrain serotonin transporter binding potential did not predict future attempts.

The authors posit that this lack may owe to low statistical power, as the study’s sample size of patients who evidenced suicidal behaviors was small.

Oquendo, who also serves as vice president of the American Foundation for Suicide Prevention, and co-authors conclude that their results suggest raphe nuclei serotonin_1A brain parenchymal fraction “represents a predictive biomarker of more lethal suicidal behavior, a serious clinical outcome.”

“Identifying neurobiological characteristics of high-lethality suicide attempters has intrinsic scientific importance,” they write, “and discovery of molecular-level markers of high-lethality behavior may eventually improve clinical screening to detect those at risk for suicide.”