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Altered neuro-inflammatory gene expression in hippocampus in major depressive disorder
Mahajan GJ, Vallender EJ, Garrett MR, Challagundla L, Overholser JC, Jurjus G, Dieter L, Syed M et al.. Progress in neuro-psychopharmacology & biological psychiatry, 2017-11-22
Topic: Brain proteins, microglia and lab models
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 up-regulated 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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APA 7th
Mahajan, G. J., Vallender, E. J., Garrett, M. R., Challagundla, L., Overholser, J. C., Jurjus, G., et al. (2018). Altered neuro-inflammatory gene expression in hippocampus in major depressive disorder. Progress in neuro-psychopharmacology & biological psychiatry. https://doi.org/10.1016/j.pnpbp.2017.11.017
Vancouver
Mahajan GJ, Vallender EJ, Garrett MR, Challagundla L, Overholser JC, Jurjus G, et al. Altered neuro-inflammatory gene expression in hippocampus in major depressive disorder. Progress in neuro-psychopharmacology & biological psychiatry. 2018. doi:10.1016/j.pnpbp.2017.11.017. PMID: 29175309.
BibTeX
@article{mahajan2018-29175309,
author = {Mahajan, G. J. and Vallender, E. J. and Garrett, M. R. and Challagundla, L. and Overholser, J. C. and Jurjus, G. and Dieter, L. and Syed, M. and others},
title = {{Altered neuro-inflammatory gene expression in hippocampus in major depressive disorder}},
journal = {Progress in neuro-psychopharmacology \& biological psychiatry},
year = {2018},
doi = {10.1016/j.pnpbp.2017.11.017},
pmid = {29175309},
url = {https://doi.org/10.1016/j.pnpbp.2017.11.017}
}
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Key findings
- Analysis revealed 30 genes differentially expressed in MDD compared to controls (FDR<0.05).
- 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.
- These findings support continued efforts to identify adjunctive approaches towards the treatment of MDD with drugs including anti-inflammatory and neuroprotective properties.
Study details
- Participants23
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Progress in neuro-psychopharmacology & biological psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 23 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29175309) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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