GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE102556 Query DataSets for GSE102556
Status Public on Aug 12, 2017
Title Sex-specific Transcriptional Signatures in Human Depression
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Rational: Major depressive disorder (MDD) is a leading cause of disease burden worldwide. While the incidence, symptoms and treatment of MDD all point toward major sex differences, the molecular mechanisms underlying this sexual dimorphism remain largely unknown.
Methods: Here, combining differential expression and gene coexpression network analyses, we provide a comprehensive characterization of male and female transcriptional profiles associated with MDD across 6 brain regions. We overlap our human profiles with those from a mouse model of chronic variable stress and capitalize on converging pathways to define molecular and physiological mechanisms underlying the expression of stress susceptibility in males and females.
Results: Our results show a major rearrangement of transcriptional patterns in MDD, with limited overlap between males and females, an effect seen in depressed humans and in stressed mice. We identify key regulators of sex-specific gene networks underlying MDD and confirm their sex-specific impact as mediators of stress susceptibility. For example, downregulation of the female-specific hub gene DUSP6 in prefrontal cortex mimics stress susceptibility in females only by increasing ERK signaling and pyramidal neuron excitability. Such DUSP6 downregulation also recapitulates the transcriptional remodeling that occurs in PFC of depressed females.
Conclusions: Together, our findings reveal dramatic sexual dimorphism at the transcriptional level in MDD and highlight the importance of studying sex-specific treatments for this disorder.
Overall design RNA sequencing data from (1) 6 human postmortem brain regions in males and females with and without major depression and (2) 2 epuivalent brain regions in males and female mice with and without 21 days of chronic varibale stress (CVS).

Note: The raw data for Samples GSM2740709-GSM2740726, GSM2740805, and GSM2740808 were updated in January 2018. The processed data have not changed.
Contributor(s) Labonte B, Engmann O, Purushothaman I, Ménard C, Wang J, Tan C, Scarpa JR, Moy G, Loh YE, Cahill M, Lorsch ZS, Hamilton PJ, Calipari ES, Hodes GE, Issler O, Kronman H, Pfau M, Obradovic A, Dong Y, Neve RL, Russo S, Kazarskis A, Tamminga C, Mechawar N, Turecki G, Zhang B, Shen L, Nestler EJ
Citation(s) 28825715, 37884562
Submission date Aug 11, 2017
Last update date Nov 13, 2023
Contact name Eddie Loh
Organization name Icahn School of Medicine at Mount Sinai
Department Department of Neuroscience
Street address 1425 Madison Avenue
City New York
ZIP/Postal code 10029
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (341)
GSM2740605 14: Orbitofrontal (OFC; BA11)
GSM2740606 17: Orbitofrontal (OFC; BA11)
GSM2740607 20: Orbitofrontal (OFC; BA11)
BioProject PRJNA398031
SRA SRP115956

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE102556_HumanMDD_fpkmtab.txt.gz 75.0 Mb (ftp)(http) TXT
GSE102556_MouseCUS_fpkmtab.txt.gz 9.3 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap