Scientists May Have Found a Genetic Marker for Suicide.
Prediction of suicidal behavior has long been considered more of an art than a science, although the use of clinical and demographic features can help improve risk assessment (see, for instance, TCPR, June 2012). An accurate biological test or “biomarker” for suicidality would be valuable, and a recent study takes us one step closer to that goal.
In preliminary work, researchers retrospectively evaluated blood samples from 75 patients with bipolar disorder, collected at multiple office visits, and found 41 genes that were expressed differentially (ie, to a significantly greater or lesser degree) when the patients expressed suicidal ideation. Of these 41, 13 were also differentially expressed (12 higher, one lower) in nine randomly-selected men from the local coroner’s office who had committed suicide. Six of these remained significantly elevated after rigorous statistical testing.
Separately, the same researchers studied gene expression in 88 men with bipolar disorder (n=42) or psychosis (n=46), and found that four out of these six genes were more highly expressed in patients who had ever been hospitalized for suicidality. The predictive power of these tests was enhanced when combined with simple questions regarding subjective measures of mood, anxiety, and psychosis.
The most predictive biomarker was a gene called SAT1, while others included PTEN, MARCKS, and MAP3K3. The SAT1 protein is an enzyme involved in the breakdown of polyamines, and overexpression of SAT1 in mice causes infertility and weight loss, among other symptoms. A gene called CD24 was underexpressed in suicidal patients, and the CD24 protein is involved in preventing apoptosis, or programmed cell death. Thus, some of the genes identified in the study seem to function in processes that may relate to cell survival.
A key strength of the study was its use of microarray technology to screen for thousands of genes at a time. Another, as noted above, was that it relied on biological measures, not interview questions, which can be unreliable. Weaknesses include the fact that subjects were all male Caucasians with bipolar or psychotic disorders (not unipolar depression). Also, samples were taken from peripheral blood, not the “target organ,” the brain. While this permitted easy collection of samples, the accuracy of such measures may be questioned (Le-Niculescu H et al, Molecular Psychiatry 2013, online ahead of print).
TCPR’S TAKE: To predict suicide on the basis of a blood test seems paradoxical, since suicide is an inherently personal decision: the ultimate in “free will,” so to speak. The current research suggests that this may not entirely be the case. But before we bring this “bench” research to the bedside of patient care, we should wait for replication of these results (including in other patient populations), and explore whether interventions to normalize or reverse these biomarkers have a protective effect.