Genetic Biomarker Tied to Suicide Risk in Schizophrenia

 July 18, 2017 – According to a new study just published in the Journal of  Psychiatric Research, a single-nucleotide polymorphism (SNP), rs300774, which previously had 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).

Overall, psychiatric disorders are being 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. A suicide attempt is the strongest predictor of suicide itself, making it imperative to accurately assess risk for attempts. The authors of the present study state that rhe 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 (GWAS) of bipolar BD suicide attempters (http://go.nature.com/2tn4t2o). In the present study, the researchers 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.

The researchers 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 (Odds ratio (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 above mentioned 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.

On the molecular level, 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 general stress response.

Taken together, the authors conclude that their findings provide additional validation of rs300774 as a potential transdiagnostic biomarker for suicide attempts and also evidence that ACP1 may have an important role in regulation of the multiple systems associated with suicide. The finding may support the decades-old hypothesis that cholesterol and related lipids in cell membranes may be involved in molecular mechanisms that eventually may lead up to suicide as the ultimate clinical phenotype in some individuals.

As always, interesting and good research opens up new questions. This is no different in this case here: To fully understand this very complex clinical phenotype, just because it is so ultimate if successful, there urgently need to be more research to understand all involved risk factors. It might well be that an extended panel of genetic and social risk factors for suicide will eventually be needed to develop a clinically useful test for prospectively identifying individuals at definitive risk for suicide attempts (which sadly enough often ends up in success). This way, individuals could be more often and more successfully be directed towards prophylactic therapies. The very shocking news of suicides, as those of Chester Bennington of Linkin Park this week and of Chris Cornell of Soundgarden just a couple of weeks before, as well as those of the countless unknown victims every week should become extreme rare over time: Intelligent research such as the one reported here will eventually contribute to this.

For those readers concerned, involved, and/or suffering: Find here a tribute worthwhile to listen to:

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About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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