期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 82, 期 -, 页码 177-186出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2017.11.017
关键词
Depression; Hippocampus; Dentate gyrus; RNA-sequencing; Neuro-inflammation
资金
- IDeA Program of the National Institute of General Medical Sciences of the National Institutes of Health
- Mississippi INBRE [P20GM103476]
- Center for Psychiatric Neuroscience (CPN)-COBRE [P30GM103328]
- Obesity, Cardiorenal and Metabolic Diseases-COBRE [P20GM104357]
- Mississippi Center of Excellence In Perinatal Research (CEPR) [P20GM121334]
- National Institute of Mental Health [R01 MH67996]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103476, P20GM104357, P20GM121334, P30GM103328] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH067996] Funding Source: NIH RePORTER
Major Depressive Disorder (MDD) is a common psychiatric disorder for which available medications are often not effective. The high prevalence of MDD and modest response to existing therapies compels efforts to better understand and treat the disorder. Decreased hippocampal volume with increasing duration of depression suggests altered gene expression or even a decrease in neurogenesis. Tissue punches from the dentate gyrus were collected postmortem from 23 subjects with MDD and 23 psychiatrically-normal control subjects. Total RNA was isolated and whole transcriptome paired-end RNA-sequencing was performed using an Illumina NextSeq 500. For each sample, raw RNA-seq reads were aligned to the Ensembl GRCh38 human reference genome. Analysis revealed 30 genes differentially expressed in MDD compared to controls (FDR < 0.05). Down-regulated genes included several with inflammatory function (ISG15, IFI44L, IFI6, NR4A1/Nur-77) and GABBR1 while upregulated genes included several with cytokine function (CCL2/MCP-1), inhibitors of angiogenesis (ADM, ADAMTS9), and the KANSL1 gene, a histone acetyltransferase. Similar analyses of specific subsets of MDD subjects (suicide vs. non-suicide, single vs. multiple episodes) yielded similar, though not identical, results. Enrichment analysis identified an over-representation of inflammatory and neurogenesis-related (ERK/MAPK) signaling pathways significantly altered in the hippocampal dentate gyrus in MDD. Together, these data implicate neuro-inflammation as playing a crucial role in MDD. These findings support continued efforts to identify adjunctive approaches towards the treatment of MDD with drugs including anti-inflammatory and neuroprotective properties.
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