Connecting the Dots: Overlapping Gene Expression Signatures in Human BNST and PTSD Across Brain Regions and Mouse Models
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The Bed Nucleus of the Stria Terminalis (BNST) serves as a regulator for long-term emotional states and is relevant to the study of post-traumatic stress disorder (PTSD). No human studies of PTSD and BNST expression have been conducted, but BNST gene expression has been studied in conjunction with stress in mice. We performed differential gene expression analyses of RNAseq data from the BNST of 8 PTSD cases and 8 PTSD/depression-free donors from the VA National PTSD Brain Bank and compared the results of an independent PTSD study of other brain regions (Girgenti et al. 2021; UPMC results) and a joint analysis of two mouse BNST studies of chronic social defeat stress (GEO GSE109315 and GSE122840). We identified 1,641 nominally significant (p<0.05) PTSD-associated BNST differentially expressed genes (DEGs; top genes CALB1, ZIC2). Although the set of significant genes did not overlap more than by chance, we found a strong correlation of effect sizes between PTSD BNST DEGs and UPMC DEGs from multiple brain regions, most strongly the OFC (r = 0.86, p = 2.2x10-16). Human BNST DEGs were not enriched for mouse DEGS (p = 0.1) and effect size estimates were not correlated (p>0.05). Although more data is needed, this study is the first step in understanding the role of human BNST gene expression and its role in PTSD genesis and maintenance.