Gene expression profiling of individuals with bipolar disorder who died by suicide and those who died from causes other than suicide in the prefrontal cortex and cerebellum

Abstract

Suicide is a major risk among individuals with bipolar disorder (BD), with up to 20% dying by suicide. However, the underlying genes and biological pathways remain poorly understood. RNA-Seq data from the prefrontal cortex (PFC) and cerebellum of Stanley Neuropathology Consortium collection were processed and analyzed to identify genes and biological pathways associated with BD as well as suicide in individuals with BD. In the PFC, 179 genes were differentially expressed in the BD patients who died from causes other than suicide (BD_NS) compared to controls, while 3 genes were differentially expressed in BD patients who died by suicide (BD_S) versus controls. Enrichment analysis identified 38 significantly enriched pathways, including inflammation and NF-κB signaling, in upregulated genes from BD_NS, but no pathways were enriched in BD_S. In the cerebellum, more genes were differentially expressed than in the PFC, with 2823 genes showing differential expression between BD_NS and controls and 26 genes between BD_S and controls. Various pathways, including synaptic vesicle cycle, endocannabinoid signaling, nicotine addiction, focal adhesion, and PI3K-Akt signaling, were enriched in the DEGs. This study suggests that biological pathways, including immune/inflammatory responses and synaptic signaling, may be associated with BD, while several genes related to cell signaling and protection against oxidative stress and DNA damage may play a role in suicide among BD patients.