Identification of potential blood biomarkers associated with suicide in major depressive disorder

Abstract

Abstract Suicides have increased to over 48,000 deaths yearly in the United States. Major depressive disorder (MDD) is the most common diagnosis among suicides, and identifying those at the highest risk for suicide is a pressing challenge. The objective of this study is to identify changes in gene expression associated with suicide in brain and blood for the development of biomarkers for suicide. Blood and brain were available for 45 subjects (53 blood samples and 69 dorsolateral prefrontal cortex (DLPFC) samples in total). Samples were collected from MDD patients who died by suicide (MDD-S), MDDs who died by other means (MDD-NS) and non-psychiatric controls. We analyzed gene expression using RNA and the NanoString platform. In blood, we identified 14 genes which significantly differentiated MDD-S versus MDD-NS. The top six genes differentially expressed in blood were: PER3, MTPAP, SLC25A26, CD19, SOX9, and GAR1. Additionally, four genes showed significant changes in brain and blood between MDD-S and MDD-NS; SOX9 was decreased and PER3 was increased in MDD-S in both tissues, while CD19 and TERF1 were increased in blood but decreased in DLPFC. To our knowledge, this is the first study to analyze matched blood and brain samples in a well-defined population of MDDs demonstrating significant differences in gene expression associated with completed suicide. Our results strongly suggest that blood gene expression is highly informative to understand molecular changes in suicide. Developing a suicide biomarker signature in blood could help health care professionals to identify subjects at high risk for suicide.