ArticleProceedings of the National Academy of Sciences of the United States of America2005
Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 305 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
305 citing papers in PubMed, 3 syntheses or guidelines pooled it, 647 citations in OpenAlex.
- TNF-α levels in first-episode, drug-naïve patients with major depressive disorder: a case-control study and meta-analysis.BMC psychiatry · 2026Pooled it
- Brain-wide changes in excitation-inhibition balance of major depressive disorder: a systematic review of topographic patterns of GABA- and glutamatergic alterations.Molecular psychiatry · 2023Pooled it
- Depression and glioblastoma, complicated concomitant diseases: a systemic review of published literature.Neurosurgical review · 2020Pooled it
- Inhibitory neurotransmission in frontostriatal circuitry: implications for psychomotor and vegetative symptoms in depressive episodes.BMC psychiatry · 2026Trial
- Fast and slow gene expression changes in blood following acute social stress.Brain, behavior, & immunity - health · 2026Article
- Multi-omics characterization of astrocyte subtypes reveals spatially coordinated astrocyte downregulation in depression.bioRxiv : the preprint server for biology · 2026Article
- The Monoamine-Glutamate Continuum of Depression: A Neurobiological Framework for Precision Psychiatry.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cefepime Alleviates Comorbid Pain and Depression Induced by Lipopolysaccharide in Female Mice.Brain sciences · 2026Article
- Astrocyte Bioenergetic Remodeling as a Central Trait of Disrupted Glucocorticoid Signaling: Mechanisms and Implications for Stress Vulnerability.Journal of neurochemistry · 2026Review
- Astrocytes: Unveiling their role in the molecular mechanism of natural antidepressants.Journal of pharmaceutical analysis · 2026Review
- The prospect of suicide biomarkers: from neurobiology to precision prevention.Frontiers in psychology · 2026Review
- Insights into Dysregulated GABAergic Synapses and Depression: A Complex and Evolving Relationship.Advances in experimental medicine and biology · 2026Review
- Deficit of neuronal EAAT2 impairs hippocampus CA3 neuron's activity and may induce depressive like behaviors.Journal of advanced research · 2026Article
- Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- The Connectomic Glutamate Framework for Depression: Bridging Molecular Plasticity and Network Reorganization.Brain sciences · 2025Review
- Chronic Stress and Astrocyte Dysfunction in Depression: Molecular Mechanisms and Gene Expression Changes.Antioxidants (Basel, Switzerland) · 2025Review
- Dynamic and Homeostatic Neuron-Astrocyte Interactions at GABAergic Synapses.Neurochemical research · 2025Review
- Proteomic Signatures of Hippocampal Nonsynaptic and Synaptosome-Enriched Mitochondria in Rats Resilient to Chronic Social Isolation.Biomolecules · 2025Review
- When the Stars Misfire: Astrocytic Dysfunctions in Major Depressive Disorder.Neurochemical research · 2025Review
- Activation of glutamine synthetase (GS) as a new strategy for the treatment of major depressive disorder and other GS-related diseases.Acta pharmacologica Sinica · 2025Article
245 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Abnormalities in L-glutamic acid (glutamate) and GABA signal transmission have been postulated to play a role in depression, but little is known about the underlying molecular determinants and neural mechanisms. Microarray analysis of specific areas of cerebral cortex from individuals who had suffered from major depressive disorder demonstrated significant down-regulation of SLC1A2 and SLC1A3, two key members of the glutamate/neutral amino acid transporter protein family, SLC1. Similarly, expression of L-glutamate-ammonia ligase, the enzyme that converts glutamate to nontoxic glutamine was significantly decreased. Together, these changes could elevate levels of extracellular glutamate considerably, which is potentially neurotoxic and can affect the efficiency of glutamate signaling. The astroglial distribution of the two glutamate transporters and L-glutamate-ammonia ligase strongly links glia to the pathophysiology of depression and challenges the conventional notion that depression is solely a neuronal disorder. The same cortical areas displayed concomitant up-regulation of several glutamate and GABA(A) receptor subunits, of which GABA(A)alpha1 and GABA(A)beta3 showed selectivity for individuals who had died by suicide, indicating their potential utility as biomarkers of suicidality. These findings point to previously undiscovered molecular underpinnings of the pathophysiology of major depression and offer potentially new pharmacological targets for treating depression.
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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.