Brain gene expression profiling studies of suicide and depression using 
oligonucleotide microarrays have often failed to distinguish these two 
phenotypes. Moreover, next generation sequencing approaches are more accurate in 
quantifying gene expression and can detect alternative splicing. Using RNA-seq, 
we examined whole-exome gene and exon expression in non-psychiatric controls 
(CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD 
non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 
9) of sudden death medication-free individuals post mortem. Using small RNA-seq, 
we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 
genes differentially expressed between groups and surviving adjustment for false 
discovery rate (adjusted P<0.1). In depression, altered genes include 
humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, 
clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene 
ontology (GO) analyses revealed lower expression of immune-related pathways such 
as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and 
angiogenesis and vascular development in (adjusted P<0.1). Hypothesis-driven GO 
analysis suggests lower expression of genes involved in oligodendrocyte 
differentiation, regulation of glutamatergic neurotransmission, and oxytocin 
receptor expression in both suicide and depression, and provisional evidence for 
altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis 
identified differential exon usage in ATPase, class II, type 9B (adjusted P<0.1) 
in depression. Differences in miRNA expression or structural gene variants were 
not detected. Results lend further support for models in which deficits in 
microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic 
cell functions contribute to MDD and suicide, and identify putative pathways and 
mechanisms for further study in these disorders.