ArticlePloS one2014
Global state measures of the dentate gyrus gene expression system predict antidepressant-sensitive behaviors.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Gene expression signatures of response to fluoxetine treatment: systematic review and meta-analyses.Molecular psychiatry · 2025Pooled it
- Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data from the Hippocampus and Cortex.bioRxiv : the preprint server for biology · 2026Article
- Antidepressants and the endogenous opioid system.Biochemical pharmacology · 2025Review
- Contribution of the Opioid System to the Antidepressant Effects of Fluoxetine.Biological psychiatry · 2022Article
- Activation of the p11/SMARCA3/Neurensin-2 pathway in parvalbumin interneurons mediates the response to chronic antidepressants.Molecular psychiatry · 2021Article
- Dentate gyrus activin signaling mediates the antidepressant response.Translational psychiatry · 2021Article
- A distinct transcriptional signature of antidepressant response in hippocampal dentate gyrus granule cells.Translational psychiatry · 2021Article
- Behavioral response to fluoxetine in both female and male mice is modulated by dentate gyrus granule cell activity.Neurobiology of stress · 2020Article
- Depression-Associated GeneCells · 2020Article
- Effect of Electroacupuncture on Reuptake of Serotonin via miRNA-16 Expression in a Rat Model of Depression.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Whole Exome Sequencing Identifies a Novel Predisposing Gene, MAPKAP1, for Familial Mixed Mood Disorder.Frontiers in genetics · 2019Article
- Article
- Treatment resistant depression: A multi-scale, systems biology approach.Neuroscience and biobehavioral reviews · 2018Review
- GluN2B-Containg NMDA Receptors on Adult-Born Granule Cells Contribute to the Antidepressant Action of Fluoxetine.Frontiers in neuroscience · 2016Article
- Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.Translational psychiatry · 2015Article
- Rodent models of treatment-resistant depression.European journal of pharmacology · 2015Review
- Mechanisms underlying the antidepressant response and treatment resistance.Frontiers in behavioral neuroscience · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSelective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common form of medication treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems respond to treatments may be critical for understanding antidepressant resistance.
methodsWe take a novel approach to this problem by demonstrating that the gene expression system of the dentate gyrus responds to fluoxetine (FLX), a commonly used antidepressant medication, in a stereotyped-manner involving changes in the expression levels of thousands of genes. The aggregate behavior of this large-scale systemic response was quantified with principal components analysis (PCA) yielding a single quantitative measure of the global gene expression system state.
resultsQuantitative measures of system state were highly correlated with variability in levels of antidepressant-sensitive behaviors in a mouse model of depression treated with fluoxetine. Analysis of dorsal and ventral dentate samples in the same mice indicated that system state co-varied across these regions despite their reported functional differences. Aggregate measures of gene expression system state were very robust and remained unchanged when different microarray data processing algorithms were used and even when completely different sets of gene expression levels were used for their calculation.
conclusionsSystem state measures provide a robust method to quantify and relate global gene expression system state variability to behavior and treatment. State variability also suggests that the diversity of reported changes in gene expression levels in response to treatments such as fluoxetine may represent different perspectives on unified but noisy global gene expression system state level responses. Studying regulation of gene expression systems at the state level may be useful in guiding new approaches to augmentation of traditional antidepressant treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.