Blood biomarkers predict suicidality

By Lucy Piper, Senior medwireNews Reporter

Researchers have found possible blood biomarkers for suicidal behavior that could help identify psychiatric patients at risk.

They identified six candidate biomarkers, with spermidine/spermine N1-acetyltransferase (SAT1) the top scoring.

SAT1 was one of 246 overlapping genes identified in blood samples taken from nine men with bipolar disorder. SAT1 expression increased in line with the men moving from a state of no suicidal ideation (as assessed on the Suicidal Ideation subscale of the Hamilton Rating Scale for Depression) to high suicidal ideation states (score of 2 or above) during the course of 24 visits, spaced 3 to 6 months apart.

The biomarker was the top scoring after cross matching to other key lines of evidence, such as human postmortem brain data and human genetic data, in a Convergent Functional Genomics (CFG) approach.

The researchers, led by Alexander Niculescu (Indiana University School of Medicine, Indianapolis, USA), then tested SAT1 levels in blood samples from nine age-matched men who had completed suicide and found they were elevated in all of them.

The increase was at least three standard deviations above the average for individuals who were in high suicidal ideation states, they comment, “which constitutes a very stringent threshold for use as a predictive biomarker.”

Indeed, 13 out of the top 41 biomarkers following CFG showed significant step-wise increases from no suicidal ideation, to high suicidal ideation state, to completed suicide; six remained significant after strict Bonferroni correction for multiple comparisons, with SAT1 still the top scoring.

The researchers also further validated SAT1 as a biomarker for suicidality in 42 patients with bipolar disorder, finding it could differentiate hospitalizations occurring as a result of suicidality from those for other reasons; this was true for both past and future hospitalizations. A further three (phosphatase and tensin homolog [PTEN], myristolyated alanine-rich protein kinase C substrate [MARCKS], and mitogen-activated protein kinase kinase kinase 3 [MAP3K3]) of the six biomarkers that remained significant following Bonferroni correction also showed similar but weaker results.

The same pattern was seen in 46 patients with psychosis, but the findings were not as strong.

“Taken together, the prospective and retrospective hospitalization data suggests SAT1, PTEN, MARCKS and MAP3K3 might be not only state markers but perhaps trait markers as well,” the team comments in Molecular Psychiatry.

Using data on mood, anxiety, and psychosis from standard scales in addition to SAT1 expression levels enhanced the prediction of future hospitalizations in a step-wise fashion, the researchers note. The area under the receiver operating characteristic curve of 0.640 with SAT1 alone improved to an area under the curve of 0.835 with SAT1, anxiety, mood and psychosis data.

“This simple clinical–genomic approach does not directly ask about [suicidal ideation], which some individuals may deny or choose not to share with clinicians,” they point out.

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