Genetic Biomarker Tied to Suicide Risk in Schizophrenia

By Marilynn Larkin

NEW YORK—A single-nucleotide polymorphism (SNP), rs300774, which has been identified as a marker for suicide in people with bipolar disorder (BD), also predicts suicide attempts in people with schizophrenia (SCZ) or schizoaffective disorder (SAD), researchers have found.

Psychiatric disorders have been reported in more than 90% of suicide completers or attempters, of whom 60% were diagnosed with BD or major depressive disorder, among other mental health conditions, according to Dr. Herbert Meltzer and colleagues at Northwestern University Feinberg School of Medicine in Chicago.

A suicide attempt is the strongest predictor of suicide itself, making it imperative to accurately assess risk for attempts, the authors observe. "The development of biomarkers for suicide risk which are transdiagnostic would be of exceptional value in the triage of individuals whose suicide risk and diagnosis is uncertain, even with knowledge of prior suicide attempts and other major risk factors.”

The researchers investigated three biomarkers for suicide attempts previously identified and replicated in a genome-wide association study of bipolar BD suicide attempters (https://go.nature.com/2tn4t2o). They hoped to replicate the previous study’s results and determine if the same biomarkers also predicted suicide attempts in patients prospectively diagnosed with SCZ or SAD.

As reported in the Journal of Psychiatric Research, online June 16, they identified 162 patients with SCZ or SAD: all Caucasian, with a mean age of 38 and mean duration of illness of 18 years. Close to half had made a serious suicide attempt.

The SNP rs300774 was the only shared genetic risk (OR=2.332) across the cohort of individuals with SCZ or SAD, as well as those diagnosed with BD in the previous study, which compared 1,201 with a history of suicide attempts versus 1,497 with no history of such attempts.

After controlling for genetic architecture and gender, the team replicated rs300774 (p=0.012) near ACP1 (acid phosphatase 1), the top predictor of suicide attempts in the BD study. Results were replicated in males (p=0.046) but not in females (p=0.205).

The other two SNPs, rs7296262 and rs10437629, were not associated with suicide attempts.

The SNP rs300774 also contributed to the expression of genes related to cholesterol biosynthesis, and subsequent analyses suggested ACP1 as important in the regulation of several brain mechanisms linked to suicide, including cholesterol synthesis, the b-catenin-mediated signaling pathway, serotonin, GABA and the stress response.

Taken together, the authors conclude that their findings provide "additional validation of rs300774 as a potential transdiagnostic biomarker for suicide attempts and evidence that ACP1 may have an important role in regulation of the multiple systems associated with suicide."

Dr. Meltzer told Reuters Health by email, “This finding supports the decades-old hypothesis that cholesterol and related lipids in cell membranes may be involved in suicide. A panel of genetic risk factors for suicide will be needed to develop a clinically useful lab test for suicide risk.”

Dr. J. John Mann, a professor of translational neuroscience at Columbia University Medical Center in New York City, commented, “The small sample makes results a bit doubtful; on the other hand, it does extend a finding from bipolar disorder to schizophrenia, so maybe it means something.”

However, “it’s not clinically useful now,” he told Reuters Health by email.

SOURCE: https://bit.ly/2taR6Hx

J Psychiatr Res 2017.

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