Brain and Blood Transcriptome Profiles Delineate Common Genetic Pathways across Suicidal Ideation and Suicide II

Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with presence of suicidal ideation were found within 18 co-expressed modules (p<0.05), as well as in 3 co-expressed modules associated with suicidal ideation severity (p<0.05, not explained by severity of depression). Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified, and investigated using RNA-seq data from postmortem brain that revealed gene expression differences with moderate effect sizes in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity are associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability. Prefrontal cortical regions, specifically the ventral white matter (BA 47), from frozen brain sections were used for RNA-seq assays. The cohort consisted of 15 suicide decedents, and 9 non-psychiatric non-suicide controls who died of accidental causes and were all free of gross neuropathology.